·Publication Number 88
AMERICAN LECTURE SERIES
A Monograph In
AMERICAN LECTURES IN PHYSIOLOGY
Edited By
ROBERT F PITTS M.D PHD
Professor of Physiology
Syracuse University College of Medicine
Syracuse New York

·HEMODYNAMICS IN
FAILURE OF THE
CIRCULATION
By
WB YOUMANS MD PHD
Professor of Physiology
Department of Physiology
University of Oregon Medical School
Portland Oregon
and
AR HUCKINS MS MD
Research Assistant
Department of Physiology
University of Oregon Medical School
Portland Oregon
das
PUBLISHER
CHARLES C THOMAS
Springfield Illinois
U S.A

·CHARLES C THOMAS PUBLISHER
BANNERSTONE HOUSE
301 397 East Lawrence Avenue Springfield Illinois
Published simultaneously in the British Commonwralth of Nations by
BLACKWELL SCIENTIFIC PUBLICATIONS LTD OXFORD ENGLAND
Published simultaneously in Canada by
THE RYERSON PRESS TORONTO
This monograph is protected by copyright No
part of it may be reproduced in any manner
without written permission from the publisher
Copyright 1951 by CHARLES C THOMAS
PUBLISHER
First ForTION
Printed in the United States of America

·PREFACE VIEWPOINTS concerning the pathologic physiology of failure of the circulation have undergone a radical change within the past ten years This article is written primarily for three classes of readers 1) those considering the subject of failure of the circulation for the first time eg medical students 2) those who have not had opportunity to do systematic reading on the subject during recent years and 3) those who wish to review the subject in the light of basic physiologic facts Others who are quite familiar with the literature on failure of the circulation perhaps will be interested to see which of varı ous controversial interpretations we have chosen to support We began the study by collecting literature contain ing pertinent measurements in patients with failure of the circulation After studying the cardiovascular patterns in the various types of failure we were impressed by the necessity of subdividing conditions associated with chronic venous congestion into two categories 1) chronic conges tive heart failure and 2) chronic venous congestion with out failure The latter group includes the conditions in which there is a higher than normal cardiac output and no evidence of cardiac weakness When this initial subdivi sion is used few inconsistencies or paradoxes are encoun tered We have presented systematically the mechanisms by means of which left ventricular failure may lead to an elevation of both pulmonary and systemic venous pres sure The prominent role of the kidney in various types of failure is described The reasons for the inconsistence of the relationship between systemic venous pressure and the status of the right ventricle are made clear We have

·Vi
HFMODYNAMICS IN FAILURE OF CIRCULATION
not used the terms backward failure or forward fail
ure because these terms have been used in many senses
so that they no longer serve as an aid to clarification of the
mechanisms involved We do not use the term back pres
sure since in a closed circuit where blood is being
pumped forward with greater or lesser speed the source
of pressure is always upstream
The bibliography includes not only references but also
other
papers
basic to the development of
present knowl
edge of the subject
W BY
ARH

·CONTENTS PREFACE V INTRODUCTION 3 1 BASIC PHYSIOLOGICAL PRINCIPLES 5 Relationship Between Ventricular Filling and Strength of Ventricular Contraction 5 Venous Pressure and Reflex Effects Upon Rate and Strength of Ventricular Contraction 9 Reflex Mechanisms Counteracting a Change in Systemic Arterial Blood Pressure 9 Comparison of Hemodynamics in the Systemic and Pulmonary Circuits 11 Immediate Changes Incident to a Decreased Cardiac Output 14 The Concept of Mean Systemic Blood Pressure or Static Blood Pressure 16 The Effects Produced by Decreasing Pump Output 17 Relationship Between Cardiac Output Renal Blood Flow and Blood Volume 21 23 23 2 FAILURE OF THE VENOUS RETURN Reduced Blood Volume Maintenance of Blood Flow in the Presence of Lowered Blood Volume Restoration of Blood Volume Physiological Rationale for Treatment Loss of Arteriolar Tonus Obstruction of Venous Drainage 23 26 26 27 80 8 FAILURE OF THE HEART 92 Acute Combined Right and Left Ventricular Failure 32 Acute Failure of the Left Ventricie 83 Chronic Failure of the Left Ventricle 98 VII

·Vilt HEMODYNAMICS IN FAILURE OF CIRCULATION
Right Ventricular Failure in the Presence of Left
Ventricular Failure
34
Acute Failure of the Right Ventricle
95
Chronic Failure of the Right Ventricle
85
True Chronic Congestive Heart Failure
36
Cardiovascular Adjustments
36
Basic Causes
98
Blood Volume
41
4 CHRONIC VENOUS CONGESTION WITHOUT
HEART FAILURE
46
Differentiation from True Congestive Heart Failure 46
Examples of the Syndrome
48
Systemic Arteriovenous Fistula
49
Beriber
54
BIBLIOGRAPHY-LEY TO PRINCIPAL SUBJECTS 58

·HEMODYNAMICS IN
FAILURE OF THE
CIRCULATION

·No text on this page.

·INTRODUCTION MAINTENANCE of the cardiac AINT output at a level within the normal range depends upon filling of the atria and hence of the ventricles under an adequate head of venous pressure, and upon a normal ventricular response to filling Since the circulation de pends upon these two major factors there are two quite different types of failure of the circulation In failure of the venous return the heart is capable of responding normally to the venous pressure but bloodus not reaching the heart in sufficient amounts This type of circulatory failųre usually is caused either by a severe decrease in blood volume or by a loss of arteriolar tonus in the systemic circuit or by a combination of these two fac tors A subnormal output of the ventricle at a given venous pressure level is caused by various types of conditions which will be classified later The essential feature com mon to such conditions is a defect in or interference with the transport of blood This defect or interference may be in the right heart pulmonary circuit left heart or systemic arteries Characteristically the pressure in the veins of the systemic or pulmonary circuit or both becomes elevated The failure initiated by insufficient return of blood to the heart is commonly referred to as peripheral circulatory failure, while heart failure strictly speaking refers to the failure of the circulation initiated by deficient transport of blood by the heart When heart failure occurs suddenly as in myocardial infarction it is called acute heart failure and when it develops more or less gradually as in patients having certain valvular lesions it is called chronic heart 3 ·4 HEMODYNAMICS IN FAILURE OF CIRCULATION failure The term decompensation is synonymous with fail ure Well established chronic heart failure is characterized by. congestion of veins cardiacılatation and dependants Pedema However there is a group of conditions in which these findings are present but in which there is no impair ment in the transfer of blood anywhere in the cardiovascular system The latter syndrome ordinarily is called heart failure also but in this paper it will be called chronic venous congestion without failure It is considered in the final section The following classification of types of failure of the circulation will be used as a basis for discussing hemodynamics I Failure of the venous return A Inadequate blood volume B Loss of arteriolar tonus C Obstruction of venous drainage II Failure of the heart A Acute combined right and left ventricular fail ure B Acute failure of the left ventricle C Chronic failure of the left ventricle D Right ventricular failure in the presence of left ventricular failure E Acute failure of the right ventricle F Chronic failure of the right ventricle G True chronic congestive heart failure Before discussing failure of the circulation certain basic principles concerning blood pressure blood flow and the distribution of blood in the cardiovascular system will be considered ·-1- BASIC PHYSIOLOGICAL PRINCIPLES RELATIONSHIP BETWEEN VENTRICULAR FILL- ING AND STRENGTH OF VENTRICULAR CONTRACTION IN A closed elastic system changes in volume and changes in pressure are inseparable An increase in volume is accompanied by an increase in pres sure the degree of rise pressure being greater the less distensible the system The rise in pressure with incre ments of volume in various parts of the cardiovascular system within the range observed in normal and path ologic physiology is not linear Curves for a section of a large vein and a section of a large artery are Illustrated in Figure 1 At the lower volumes introduction of a given volume causes a lesser rise in pressure than that produceda by the same increment in volume at a higher volume level. This is equivalent to saying that a given rise in volume in a relatively unfilled portion of the cardiovascular tree walls result in a slight increase in pressure while the same degree of increase in volume in a filled portion of the cardiovascu lar tree will result in a considerable rise in pressure Several decades ago Starling and associates studied the relationship between ventricular filling (and consequently of diastolic ventricular size) and the strength of ventricular contraction Starlings law of the heart based on these data states that the strength of ventricular contraction increases with increasing diastolic ventricular size up to a certain optimal value beyond which an increase in di astolic volume is associated with a decreased strength of 5 ·6 HEMODYNAMICS IN FAILURE OF CIRCULATION 180 160 140 120 100 aunssand OH W Axlery 80 60 40 20+ O 0 10 20 30 40 50 80 70 80 90 100 CC volume FICURE I Relationship between intravascular pressure and volume The upper curve represents an isolated segment of a large artery the lower cune a segment of a large vein A giverz volume of Auid introduced into a collapsed vein will cause a slight pressure increase while the same vol ume introduced into a distended vein will cause a marked increase in pressure Particular attention should be given to changes within the physiologic range of pressure in each type of vessel (After Best & Taylor Physiological Basis of Medical Practice 4th Ed Page 123 ) contraction At a given heart rate diastolic heart size is determined largely by the head of pressure in the great veins and atria Any increase in venous pressure within the normal range in a Starling heart lung preparation in which reflex pathways are eliminated will cause increased ventricular filling increased strength of ventricular con traction and increased stroke volume against constant mechanical conditions on the arterial side Heart rate re ·BASIC PHYSIOLOGICAL PRINCIPLES 7 mains virtually unchanged hence cardiac output is in creased in proportion to the increased stroke volume However when the venous pressure is already quite ele vated a further increase in pressure as illustrated in Figure 2 results in decreased stroke volume and a corre sponding decrease in cardiac output In brief there is an increased cardiac output through increased filling and increased strength of ventricular con traction as the venous pressure is increased up to a certain critical level beyond which a rise in venous pressure causes a decrease in cardiac output Throughout this paper it is accepted as a fact that any cardiac output Right auricular pressure FIGURE 2 Changes in cardiac output in response to changes in right auricular pressure in the absence of neural or humoral influences for the normal heart (above) and for the weakened heart (below) This illustrates that for a given filling pressure the output of the weakened heart is less than for the normal on the other hand the weakened heart may attain an output in the normal range in the presence of a higher than normal venous pressure ·8 HEMODYNAMICS IN FAILURE OF CIRCULATION alteration in venous pressure per se influences output of either the normal or the failing heart However there are other influences working simultaneously in the same or the opposite direction and cardiac output during a given period is the resultant of these influences It is an unfortu nate choice of words to say that Starling s law is not operat ing when an increased cardiac output is associated with a decreased venous pressure as for example from increased activity of the cardio accelerator nerves In such cases the cardiac output is certainly less than it would be if the ve nous pressure were maintained in the presence of this de gree of cardio-accelerator activity Starling s law of the heart not only affords a basis for an increased cardiac output in response to increased ve nous pressure but it also is concerned in the maintenance of cardiac output against an elevated arterial blood pressure In the heart lung preparation as the arterial pressure is elevated the amount of blood remaining in the heart at the end of systole is increased and during diastole the heart fills to a larger size This causes an increased strength of contraction which in this case serves to eject the same volume of blood against the increased resistance Again a critical arterial pressure may be reached beyond which the diastolic ventricular size becomes excessive and against which the ventricle cannot pump so that a fall in cardiac output will result In summary the relationship between initial length of ventricular muscle and the strength of its contraction is such that within limits l) an increased venous pressure causes an increase in cardiac output and 2) cardiac output is maintained in the presence of an increased arterial blood pressure ·9 BASIC PHYSIOLOGICAL PRINCIPLES VENOUS PRESSURE AND REFLEX ETFECTS UPON RATE AND STRENGTH OF VENTRICULAR CONTRACTION In addition to the adjustments of the cardiac output to venous pressure on the basis of changes in diastolic heart size there are reflexes elicited by a rise in venous pressure which also serve to increase output The reflex increase in heart rate under these conditions is known as the atrial ar Bainbridge reflex Since the sympathetic pathways provide the efferent limb a reflex increase in the strength of ven tricular contraction probably is involved also The afferent fibers for the reflex are contained in the vagus nerve Thus in the intact circulation a tise in venous pressure may be expected to cause an increase in cardiac output on the basis of Starling s law of the heart and the Bainbridge reflex A rise in venous pressure can be produced in man by rapid intravenous administration of fluid In most studies this has resulted in an increase in cardiac output in proportion to the rise in venous pressure (3 99 186 200) REFLEX MECHANISMS COUNTERACTING A CHANGE IN SYSTEMIC ARTERIAL BLOOD PRESSURE response of the heart to the arterial blood pressure insofar as the response in based on Starling s law is such as to maintain an unchanging output in the presence of a changing arterial pressure Under physiological condi tions and some pathological conditions there are consider able changes in resistance to outflow from the arterial tree due to changes in the state of contraction of the smooth muscle in the arterioles (119) Changes in cardiac output in response to changes in arterial pressure are accom plished largely through the carotid sinus and aortic arch reflexes The ·10 HEMODYNAMICS IN FAILURE OF CIRCULATION Afferent fibers concerned with these reflexes pass from the aortic arch via the vagi bilaterally and from the two carotid sinuses via branches of the glossopharyngeal and vagus nerves on the efferent side the pathways involved are diffuse both the sympathetic and parasympathetic nerves to the heart and blood vessels are utilized These reflexes operate as follows The degree of activation of re Right Heart Systemic Circuit Pulmonary Circult Left Heart FIGURE 3 Dragram of the circulatory system The portion in which the mean pressure exceeds 25 mm of mercury is stippled The mean pressure gradients are shown in Figure 4 ceptors in the carotid sinuses and aortic arch varies with sudden changes in the pressure level A rapid increase in pressure results in an increase in the number of impulses passing from the receptors up the afferent nerves to the medulla oblongata By means of connections in tlie medulla the number of impulses passing out over the (vagal) cardio-inhibitory nerves is increased while the activity of the cardio accelerator nerves (mainly sympa thetic) is decreased At the same time the tonic activity of yasoconstrictor nerves (contained largely in the sympa ·BASIC PHYSIOLOGICAL PRINCIPLES 11 thetic system) is decreased and possibly vasodilator nerves are activated Thus the rise in arterial pressure is counter acted reflexly both by a decreased input of blood into the arterial system and by a decreased resistance to outflow from the arterial tree A fall in blood pressure as seen during liemorrhage has the reverse effects since it is associated with a decrease in the number of impulses initiated in the receptors of the aortic arch and carotid sinuses COMPARISON OF HEMODYNAMICS IN THE SYSTEMIC AND PULMONARY CIRCUITS Since normally there is no flow of blood directly from the left side of the heart to the right side the circula tory system may be diagrammed as in Figure 3 Although anatomically there are two circuits when the route of a unit of blood is considered there is one circuit con taining_two separate pumps the right heart and the left heart The volume of blood flow per unit of time at any cross section of the system cannot be different from the flow at any other cross section for very long otheru ise blood would progressively accumulate at some site in the system Momentary differences in flow in the two circuits do occur under certain conditions and are associated with transfer of blood from one circuit to the other On the other hand during any prolonged period the output of the right ventri le must equal the output of the left ventri cle Since the right ventricle maintains an output equal to the output of the left ventricle and the mean pressure in the pulmonary artery is approximately one sixth the mean pressure in the aorta it is evident that the resistance to flow of blood through the pulmonary circuit 15 a small fraction of the resistance to flow in the systemic circuit The difference in amount of work done by the two ventri cles is approximately proportional to the difference in te sistance to flow The pressures throughout the two circuits ·12 HEMODYNAMICS IN FAILURE OF CIRCULATION are shown in Figure 4 which also illustrates that the mean length of the systemic circuit is much greater than that of the pulmonary circuit The fraction of the total blood volume contained in the pulmonary circuit is small compared to the amount con tained in the systemic circuit Figures obtained by various 100% 90 Boy 701 80 501 200 or Arte Arti Left Heart Rint 77 Wert 4 lar Aorts Aerta SYSTEMIC CIRCUIT Pul MoMARY CIRCUIT FICURE 4 Mean pressure gradients in the systemic and pulmonary ar cuits Vertically the pressure scale in mm of mercury is shown Horizon tally the relative mean lengths of the two circuits are roughly illustrated This figure should be studied along with Figure 3 to visualize changes in distribution of blood associated with changes in pressure and volume in the systemic arteries methods indicate that 12 to 20% of the blood volume is contained in the pulmonary circuit Under normal condı tions alterations of this fraction ie shift of blood from the systemic circuit to the pulmonary circuit or the re erse is accomplished through alterations in vasoconstric tor tonus in the systemic circuit Vasodilatation allows the blood to pool in the large systemic capıllary bed and the Volume of blood in the pulmonary vascular bed is propor ·BASIC PHYSIOLOGICAL PRINCIPLES 13 tionately decreased Conversely widespread systemic vaso construction will result in transfer of blood into the pul monary vascular bed and, at the same time cause an in crease in pressure in the pulmonary capillaries Thus the lungs function as an important blood reservoir more or less passively accepting whatever volume is transferred from the systemic circuit There is evidence that the pul monary arterioles like the systemic arterioles are supplied with vasomotor nerves from the autonomic nervous system but the degree of their influence is debatable It is obvious from the relative volumes in the two circuits under normal conditions that a sudden transfer of blood from the sys ternic uit into the pulmonary circuit from any cause could engorge the pulmonary circuit but the amount of blood that could shift from the pulmonary circuit to the systemic circuit would not be sufficient to flood the sys ternic circuit When the blood volume is increased above the normal level (plethora) it is accommodated largely in the capıllary beds Experimentally plethora of a degree which alone will not produce pulmonary edema when combined with vasoconstriction will produce pulmonary edema with great rapidity since enough blood will be shifted into the pul monary system from the systemic capillary bed to produce a rise in hydrostatic pressure sufficient to cause transuda tion of fluid into the alveoli Knowledge of these facts concerning the two circuits is necessary for an understanding of failure of the rcula tion Although heart failure frequently involves disturb ances in the flow of blood in certain types of failure and in certain stages of chronic congestive failure the disturb ances in volume and distribution of blood are striking while changes in blood flow are minimal (136) ·14 HEMODYNAMICS IN FAILURE OF CIRCULATION IMMEDIATE CHANGES INCIDENT TO A DECREASED CARDIAC OUTPUT The immediate effects of a decrease in cardiac output on arterial pressure and venous pressure have been de scribed by Starlıng (158) Starr (164) and others who have made use of two-circuit artificial circulation models to illustrate some of the changes which occur Start re cently lias used a one-circuit schema (160) In this laboratory a simple one-circuit model having certain characteristics of the cardiovascular system is used to illustrate the direction of the initial changes in arterial and venous pressure produced by alterations in cardiac out put and peripheral resistance The essential features of the model are as follows 1 A motor druen piston pump capable of various rates and various stroke volumes and two check valves to main tain one way flow 2 A closed elastic system Elasticity is obtained on the arterial side by air filled thin rubber tubing attached to an upright side arm which can be closed off by means of a gate valve Elasticity and reservoir function are obtained on the venous side by the use of an air dome of appropriate size 3 Peripheral resistance of any desired degree is obtained by a gate valve 4 Fluid is introduced into the system from a pressure bottle until the volume is such that a positive pressure is produced the pump being at rest Lateral pressure is re corded from the arterial side and from the venous side by means of two manometers In such a system when either pump output of periph eral resistance is altered the change in venous pressure is in the reverse direction of the change in arterial pres sure When blood volume is increased both venous and

·BASIC ITIYSIOLOGICAL PRINCIPLES
A Nmal
It
0
O
ON
I
B. Dump output de eased
แต่
C. Fluid volume increased
FICURE 5 Schema of a one at putt circulation mod I designed to illus
Irate initial changes in pressure and olume on the arterial and venous
side produced by altering pump output fluid volume or peripheral resist
ance Essential features of the model are described in the text Figure o is
made from a kymographic record of the pressure chan.cs
A Vormal conditions simulated
B Decrease in pump output
C Increase in blood volume
This is the simplest schema to illustrate initial changes since no com
pensation can occur by either neural or humoral Influences or by Starlings
Jaw The compensatory mechanisms when present do not alter the direc
tion of the initial change but reduce the degree

·16 HEMODYNAMICS IN FAILURE OF CIRCULATION associated with increased pulsations and negligible mean pressure changes throughout the system The changes in systolic diastolic and pulse pressure with changes in rate stroke volume and peripheral resistance are as produced in the various other circulation models designed to illus trate changes in arterial pressure The Concept of Mean Systemic Blood Pressure (158) or Static Blood Pressure (9 164) Essential features of any circulation model which is designed to illustrate changes in venous pressure are that the system be closed and that sufficient fluid be introduced so that a positive pres sure is produced throughout the system with the pump at rest That such a relationship exists in the mammalian circulation is indicated in several ways In the first place it can be inferred from the fact that the mean pressure recorded at any point in the system is positive when the heart is beating It is obvious that cessation of heart action would be followed by a fall in pressure and volume in the arteries where the pressure is high and a rise in pressure and volume in the venous system where pressure is low until the pressure throughout the system becomes equal This pressure must be positive unless the contractile ele ments of the vascular bed relax and thus increase the capacity of the system when the heart stops Actually in the intact animal when cardiac output suddenly decreases or ceases the fall in arterial blood pressure elicits a severe contraction of the arterioles and probably there is an in creased venomotor tonus so that the capacity of the cardiovascular system decreases In the second place the static pressure can be demon strated experimentally If asystole is produced and main tained by stimulation of the peripheral end of the sec tioned vagus (in an eserinized dog) arterial blood pressure falls and venous pressure rises so that the levels approach each other (80) A similar result is observed if the circula ·BASIC PHYSIOLOGICAL PRINCIPLES 17 tion is brought to an abrupt stop by ventricular fibrilla tion or by cardiac camponade (184) The static pressure is not high since the veins normally are relatively unfilled and will accommodate the considerable rise in volume with only a moderate rise in pressure Start has shown that a static pressure is present in patients for some min utes after cardiac arrest (159) The static pressure averaged 72 cm in 25 patients who did not have congestion or cardiac abnormality whereas in 10 patients who died in congestate heart failure it averaged 20 7 cm It is con sidered that the increased level of the static blood pressure under these conditions is related in large part to increased blood volume The Effects Produced by Decreasing Pump Output In the artificial schema at a given pump output a constant pressure gradient is maintained in the system and there is a constant rate of flow from the arterial side to the venous side Any desired difference between arterial and venous pressure is obtained by adjusting the peripheral resistance a relatively high resistance being required to obtain a wide difference between these two readings When the pump output is decreased either by decrease in rate or stroke volume the rate of outfiow from the arterial side does not immediately decrease to the lower level of input into the arterial side Outflow from the arterial side ex ceeds the pump input for a brief period as the arterial pressure falls off to a lower level The distended artenes serve as the source of energy to promote this transfer of fluid to the venous side Thus when the resistance to outflow is constant the degree of distention of the elastic system that will be maintained depends upon the rate of input into the system For any level of input into the system a given degree of distention is established and out put is equal to input In short when there is a decrease in output of the pump ·18 HEMODYNAMICS IN FAILURE OF CIRCULATION there is a brief period during which more fluid flows to the venous side than is transferred by the pump from the venous to the arterial side Thus there is a decrease in pressure and volume on the arterial side and an increase in pressure and volume on the renous side until a new equi librium is established The changes in pressure are illus trated in Figure 6 The extent of the rise in pressure on the WI AP SP VP DEC HR DEC SV DEC BV ON FIGURE 6 Efects of changes in tole stroke volume and blood volume upon arterial pressure (A P) and venous pressure (1 P) in the circula fion schema This figure should be studied in conjunction with Figure 5 The straight line indicates the pressure throughout the system when the pump is at rest This pressure is brought up to any desired level by introducing fluid into the closed elastic system The first record illustrates the progres sive increase in "arterial pressure and decrease in venous" pressure unul an equilibrium 13 established when the pump starts suddenly at a given output The peripheral resistance 1 at a relatively high level as in the systemic circuit of the cardiovascular system The second record shows the fall in "arterial pressure and rise in venous pressure which occurs when the rate of the pump suddenly is decreased with stroke volume remaining unchanged The third record Jlustrates the similar changes in mean pressures when stroke volume is decreasing with rate remaining constant in the fourth record the effects of decreasing the blood olume are illus trated in this case static pressure also falls in proportion to the fall in blood volume Changes in rate and strole volume have addiuve elfects when they are both decreased of both increased and effects on the pressures are ncutral med when one is focsasad while the other is decreased.

·BASIC 1 111 SIOLOGICAL PRINCIPLES 19 venous side associated with a decreased pump output de pends 1) upon the extent to which the venous side was filled prior to the decrease in output and 2) upon the distensibility of the venous system The energy for transfer of blood from the arteries to the veins when cardiac output decreases comes from the distended arteries Decreased output of the heart either in the mammalian circulation or in artificial schemas of the type described 15 accompanied by a redistribution of blood towards the venous side and a rise in Tenous pressure In the artificial circulation schemas the rise in venous pressure is produced entirely as a direct result of the decreased output In the intact circulation it must be considered that a decreased output per se could contribute to the observed rise in venous pressure in the same way that it does in the circula tion models but also as soon as arterial blood pressure is lowered and venous pressure is elevated certain well de fined compensatory mechanisms are immediately brought into action By means of carotid sinus and aortic arch re flexes the fall in arterial blood pressure causes cardiac ac celeration and an increase in arteriolar tonus Decreased blood flow in the medulla oblongata and possibly else where in the brain promotes increased vasoconstrictor tonus The rise in venous pressure elicits the Bainbridge cardiovascular reflex Ventricular filling is improved by the rise in venous pressure and through Starling s law more forcible contractions are stimulated Thus the extent of fall in arterial pressure which tends to be produced by a given degree of impairment of left ventricular action is not as great as it would be in the absence of these compensatory mechanisms It should be noted that the vasoconstruction which is elicited by a fall in blood pressure while serving to oppose the fall in arterial blood pressure contributes to further transfer of blood into the large veins of the sys temic and pulmonary circuits and thus favors a further Tise in venous pressure ·20 HEMODYNAMICS IN FAILURE OF CIRCULATION In summary the immediate effect of a decrease in cardiac output is a fall in arterial blood pressure and a rise in venous pressure The rise in venous pressure occurs because outflow of blood from the arterial tree exceeds input for a brief period until a new equilibrium is estab lished with a greater volume of blood in the large veins of both circuits In the second place a further increment in central venous pressure is produced by the transfer of blood into the veins incident to reflex vasoconstriction which is elicited from the fall in arterial blood pressure Reflex venoconstriction may be concerned temporarily in promoting a further rise in venous pressure (37) The rise in venous pressure has compensatory value in that it stimulates the heart so that the fall in cardiac output is not as great as it would be if the venous pressure were not elevated At this point it may be re emphasized that the maximum increase in the volume of blood in the venous system that can be produced immediately following a decrease in cardiac output eg as seen from cardiac arrest or cardiac tamponade in the presence of a normal blood volume does not produce a rise in venous pressure as high as that seen in chronic congestive failure Blood redistribution is only one of several factors contributing to the rise in venous pressure in chronic failure Severe venous congestion incident to heart failure does not develop instantaneously and during the hours days or longer required for its de velopment the blood volume and interstitial fluid become elevated Since the rise in central venous pressure to the levels seen in chronic congestive heart failure appears to be dependent to a considerable degree upon an increase in the blood volume and an increased extravascular support the explanation for the rise in venous pressure resolves itself largely into an explanation for the rise in volume of the extracellular fluid (blood plasma and interstitial fluid) ·BASIC PHYSIOLOGICAL PRINCIPLES 21 RELATIONSHIP BETWEEN CARDIAC OUTPUT, RENAL BLOOD FLOW AND BLOOD VOLUME The relationship between cardiac output and blood volume and the essential role of the kidney in this rela cionship has been discussed at length by Borst (10) In various conditions in which there is a decreased cardiac output the renal blood flow has been found to be dispro portionately decreased This is true whether cardiac out put is decreased because of a decreased venous return or because of heart failure (106 109 111, 132) Merrill (106) found in a series of 35 patients in whom the cardiac out put was about 40% of normal that the renal blood flow was about 25% of normal Molotoff et al (111) report an even greater decrease in renal blood flow Borst (10) has presented evidence that any decrease in cardiac output probably through changes in renal function caused by de creased renal blood flow leads to a reduction in the ex cretion of sodium chloride (and hence of water) so that the blood volume becomes elevated The increase in blood volume would serve to cause a rise in venous pressure which would be expected to stimulate the heart to a higher output Thus Borst views the retention of sodium chloride by the kidney in response to a decreased cardiac output as a homeostatic mechanism serving to restore the cardiac output The sequence of events postulated is sum marized as follows Decreased cardiac output (€g from myocardial weakness) Decreased renal blood flow Retention of sodium chloride and water + Increased blood volume Increase in venous pressure Rise in cardiac output toward the normal level ·22 HEMODYNAMICS IN FIILURE OF CIRCULATION According to this view the rise in blood volume should be self limiting As the cardiac output approaches normal there is elimination of the basis for further retention of salt and the end result if the original cause for the de creased output persists is that a relatively normal output is attained through an elevated blood volume and venous pressure McMichael has repeatedly emphasized the view that the rise in venous pressure in heart failure is a device for main taining a cardiac output within the normal range (97 99) The recognition of the fact that renal function of a patient in congestive heart failure is different from the normal subject has stimulated many recent studies Some important results of these studies will be discussed later Merrill and Stead and Warren contrary to Borst believe that the decreased sodium excretion associated with de creased renal blood flow should be viewed as being on the basis of impairment of renal function rather than as a homeostatic mechanism It appears that the choice of terms to apply to the phenomenon of sodium retention is de termined by the difference in views concerning the value of the concomitant rise in blood volume and venous pres sure rather than by any difference in viewpoint regarding the actual renal mechanisms involved The latter workers are less impressed than McMichael and Borst by the compensatory value of a mild or moderate rise in venous pressure and are more impressed with the difficulties en countered when the rise in venous pressure is excessive ·- --2- FAILURE OF THE VENOUS RETURN REDUCED BLOOD VOLUME WHEN HEN the blood volume is re duced compensatory mechanisms are brought into activity which help to maintain adequate flow of blood to vital organs Other mechanisms which act more slowly serve to restore the normal blood volume Maintenance of Blood Flow in the Presence of Lowered Blood Volume The principal immediate responses to a sudden considerable decrease in blood volume eg from hemorrhage are shown in Figure 7 Loss of blood results in a fall in both arterial and venous pressure and each of these changes elicits compensatory responses The fall in arterial blood pressure is opposed by nervous and humoral mechanisms The falling pressure in the carotid sinuses and aortic arch results in reflex cardiac acceleration reflex Jasoconstriction, and probably venoconstruction The vaso construction is accomplished on the efferent side largely through the activation of adrenergie nerves and is supple mented by reflex liberation of epinephrine The vasocon striction helps to restore arterial blood pressure by imped ing the outflow from the arterial tree and hy promoting the transfer of blood into the venous system from blood reservoirs, tends to restore venous pressure The combina tion of rapid heart rate and low venous pressure results in a low difference between systolic and diastolic pressure le pulse pressure is decreased. The left side of the dia tam indicates a humoral mechanism for production of asoconstriction in the presence of a chronically lowered blood volume The decreased renal blood flow is associated 23 ·24 HEMODYNAMICS IN FAILURE OF CIRCULATION severely decreased bioad volume Decreased arterial blood pressure Decreased vanous blood pressure Decreased renal blood flow Decreasad pressure in carotid sinuses and aortic arch Decreased ventricular filling Decreased glomerular filtration Renin production VEM Epinephrine Tiberation Angiatonin Oligurta for Arxurla Decressed Sodium lexcretion Vasoconstriction Cardiac acceleration Decreased pulse pressure FIGURE 7 Mechanisms concerned aeth development of the typical cardio vascular pattern seen when the blood volume is severely decreased with production of renin an enzyme acting upon a constit uent of normal blood plasma to produce angiotonin a vasoconstrictor substance (34 60 76 120) The neural vasoconstrictor mechanism is elicited immediately whereas the humoral mechanism is more sluggish However the angiotonin mechanism appears to be suitable for main tenance of a more sustained vasoconstriction and in some ·FAILURE OF THE VENOUS RETURN 25 degree replaces the reflex mechanism which is less suitable for prolonged function As discussed by Ogden (118) it appears that some other mechanism replaces the angiotonin mechanism when there is a prolonged decrease in renal blood flow According to the work of Chambers and Shorr and others (24 153) when the kidney is subjected to deficient circulation by various methods it produces a vaso-excitor material (VEM) which increases the sensitivity of arterioles to the constrictor action of epinephrine This substance may be concerned in part with the compensatory vasocon striction in shock However in later stages of shock a vaso dılator material (VDM) is said to enter the circulation in progressively increasing amounts possibly contributing to production of irreversible shock In a discussion of measurements obtained from patients suffering from traumatic shock Richards (132) states the essential finding in all appeared to be an inadequate venous return of blood to the heart with diminished cardiac output The anatomical factor immediately te sponsible in most instances was a deficit in circulating blood volume The studies reported by Richards demon strate selectivity of the vasconstrictor response in shock the blood flow through the kidney being reduced in some cases to 1/10 or 1/20 of the normal value when the cardiac output was reduced to one half the normal level The great fall in renal blood flow is interpreted as indicating that re sistance to blood flow through the kidney is dispropor tionately increased by severe constriction of the renal arterioles Since & relatively large part of the cardiac out put goes through the kidneys the advantage to other organs of a temporarily lowered renal blood flow in shock is clear However oliguria or anuria results and finally there is damage to the renal tubules of ischemia is pro longed ·26 HEMODYNAMICS IN FAILURE OF CIRCULATION o There are also central mechanisms for production of vasoconstriction in the presence of a decreased blood volume As blood flow through the medulla oblongata de creases the carbon dioxide tension in the medulla in creases and this stimulates the vasoconstrictor center When the blood volume has been severely decreased for a more or less prolonged period the arterioles apparently lose their ability to remain contracted in response to the usual stimulating agents A loss of arteriolar tonus will cause a decrease in Lenous return even in the presence of 3_normal blood volume? and the deleterious effects of arteriolar relaxation are greater in the presence of a "owered blood volume when this stage is reached trans fusions are relatively ineffective in increasing blood pressure since the blood pools in the capıllary beds The reader can refer to Wiggers (196) for a detailed discussion of vasomotor reactions in the various stages of shock Restoration of Blood Volume In the presence of a de crease in blood volume the decrease in hydrostatic pressure in the capillaries which is secondary to decreased volume and arteriolar constriction promotes transfer of fluid from the interstitial space into the blood stream Thus the fall in blood volume is counteracted at the expense of the inter stitial fluid To a lesser degree intracellular fluid the interstitial space The transfer of fluid into the blood from the interstitial space is reflected in a rapid decrease in the volume of red blood cells per unit of blood (hematocrit) The bone marrow is stimulated probably by lowered oxygen tension gradually restoring the hematocrit to norm Physiological Rationale for Treatment The treatment in the syndrome of inadequate blood volume is directed at restoration of the venous return so that cardiac filling and hence cardiac output may be improved It consists firstly of measures which will assist venous return until 3 passes into ·FAILURE OF THE VENOUS RETURN 27 the blood volume can be restored and secondly of ad ministration of blood or blood substitutes Even though physiological saline solution is lost from the circulation following intravenous injection it may be valuable for maintaining circulation for a short period until blood or plasma is available The flow of blood to the heart may be improved by elevation of the foot of the bed This results in an increased central venous pressure and consequently an increased cardiac output Vasoconstrictor compounds bare not proved to be of much value in the treatment of this syndrome In the reversible stage, there is_already severe vasoconstriction produced by the compensatory mechanisms described above In the later._stages_the arterioles fail to maintain their tonus in response to either the nerions_nr humoral mechanisms and therefore would be expected to be relatively unresponsive to pharmacologic vasoconstrictor agents Finally a positive salt and water balance also would be expected to occur through the mechanisms diagrammed in Figure 7 and this would assist in restoration of normal Volumes in the fluid compartments LOSS OF ARTERIOLAR TONUS The tonus of the smooth muscle in the arteriolar wall is under the influence of vasconstrictor and to a lesser degree vasodilator nerves These nerves constitute the final common path for various reflexes that influence ar teriolar conus for central effects related to changes in blood composition (especially in Co, and pH) and for psychic effects Most of the vasoconstrictor nerves are adrenergicie exert their action on arteriolar smooth muscle through the liberation of epinephrine or an epinephrine lıke substance A widespread inhibition of arteriolar tonus usually associated with a decrease in heart ·28 HEMODYNAMICS IN FAILURE OF CIRCULATION rate may be produced on a reflex basis by massaging the carotid sinus Neurogenic vasodilatation commonly is associated with emotions Loss of arteriolar tonus may be produced by injection of vasodilator.compounds such as doryl (carbaminoyl choline) or urecholine (carbaminoyl beta methyl choline) or by administration of agents like Dibenamine (dibenzyl beta chloroethylamine) which black the action of the adrenergic vasoconstrictor nerves One of the primary physiologic functions of the vaso constrictor nerves is to prevent pooling of blood in the por tion of the body below the level of the heart Therefore these nerves are particularly important in man in the standing position When a subject is in the reclining posi tion there is only a mild degree of tonic ie continuous activity of the vasoconstrictor nerves This is evident from the effects on blood pressure and heart rate following administration of an adrenergic blocking agent such as Dibenamine While the subject is supine there is usually either no change in blood pressure or a slight decrease and typically there is a slight increase in heart rate The effects of the drug appear negligible until the patient stands then the blood pressure drops precipitously due to pooling in the dependant part of the body The adrenergic cardioaccelerator innervation is not blocked by Dibenamine and the heart is reflexly accelerated as a result of the fall in pressure in the carotid sinuses and aortic arch Under normal conditions when an individual changes from the supine to the upright position reflex activation of the vasoconstrictor pathways is elicited by the rise in pressure in the splanchnic vascular bed (68) and by any fall in pres sure in the carotid sinuses and aortic arch There is also re flex cardiac acceleration from the latter receptors In the patient under the influence of Dibenamine the efferent pathways are activated following changes in blood pres ·FAILURE OF THE VENOUS RETURN 29 75 20 A 50 35 B 100 10 c 1 Artery Arterid Cap llary Vein FIGURE 8 Effects of allerations in arteriolar fonus upon pressure and olume in the capillaries The figures are arbitrary and serve only to show direction of change A Yormal conditions B As the arterioles telar the arterial pressure decreases and the pressure in the capillaries increases. A slight increase in pressure in the capillaries 15 associated with a large increase in volume Rise in arterial pressure and decrease in capillary pressure resulting froid arteriolar constriction sure but the chemical mediator produced at the adrenergic vasoconstrictor nerve endings is incapable of causing con traction of the smooth muscle in the arterioles thus alloty ing the blood to enter the distensible capillaries under an increased head of pressure The effects of changes in arteriolar tonus upon pressure and volume in the capil laries is shown graphically in Figure 8 If the patient re mains in the upright position he may faint as a result of inadequate cerebral circulation If the patient is re ·80 HEMODYNAMICS IN FAILURE OF CIRCULATION turned to the horizontal position circulation quickly re turns to normal The relation of activity of skeletal musculature to Venous return becomes obvious in a patient who has re cerved a large dose of an adrenergic blocking agent The patient may faint within one or two minutes after assum ing the upright position if he stands still but if he walks circulation may be maintained Also circulation may be maintained if a tight abdominal binder is applied A circu latory syndrome similar to that produced by Dibenamine occurs spontaneously or idiopathically in some individu als and is known as orthostatic hypotension The compensatory responses initiated by a sudden gen eralized loss of arteriolar tonus are similar to those which are initiated by a decrease in blood volume This is true because in each case there is a fall in both arterial and venous pressure and most of the compensatory reactions are secondary to these two changes Renal blood flow is disproportionately decreased when there is generalized loss of arteriolar tonus since other vascular beds normally offering higher resistance to blood flow are opened Under these conditions it is probable that there is a decreased ex cretion of salt The most prominent manifestations of a chronıc decrease in arteriolar tonus (or more generally of a decreased resistance in the systemic circuit) are in creased blood volume and increased cardiac output The mechanisms concerned with production of these changes are discussed on pages 23ff OBSTRUCTION OF VENOUS DRAINAGE Obstruction of a large systemic vein produces hemody namic changes sımılar to those produced by loss of blood or by generalized vasodilatation Pressure upstream from the obstruction approaches arterial pressure and the blood ·FAILURE OF THE VENOUS RETURN 31 trapped in the capillaries and veins is not available for circulation The venous return to the heart decreases venous pressure and hence cardiac output and arterial pres sure decrease These effects may be demonstrated by clamp ing the portal vein As blood continues to flow into the splanchnic vascular bed and cannot flow out the circulat ing blood volume decreases Venous pressure decreases cardiac output and arterial blood pressure decrease pre cipitously and cardiovascular compensatory reflexes are initiated When one breathes into a bag containing gases under a pressure greater than atnospheric pressure there is partial obstruction to the entire systemic venous drainage plus an increased resistance to flow of blood through the pulmo nary circuit (430) Barach et al (4) state The blood merely accumulates in the great veins until the pressure inside them is high enough to overcome the added external pressure The circulation is maintained at a higher level of intra auricular pressure but cardiac filling is at best not increased and may be decreased The rise in venous pressure is aided by two other processes (1) The displacement of blood from the lungs increasing correspondingly the Volume of blood in the systemic circulation and (2) in creased tone of the arteries and/or veins in the legs The increased resistance to flow of blood through the lungs 19 overcome by an increased strength of contraction of the right ventricle so that an output near normal is maintained ·--3- FAILURE OF THE HEART ACUTE COMBINED RIGHT AND LEFT VENTRICULAR FAILURE THE most extreme examples of simultaneous acute failure of the pumping action of both ventricles are cardiac standstill and ventricular fibrillation In each case pumping action of both ventricles suddenly ceases and there is no longer a basis for maintaining the pressure gradients in either the systemic or pulmonary circuits Blood volume and pressure decrease precipitously in the systemic arteries and increase in the systemic and pulmonary veins and in the atria Shortly pressure is equal throughout the circulatory system at the relatively low static pressure level If the pumping action of both ventricles is decreased eg by toxic action of certain drugs on the myocardium or by an excessively fast heart rate resulting in a sudden de crease in cardiac output of a degree compatible with life both immediate and delayed adjustments occur The im mediate adjustments elicited by decreased cardiac output are those already described on pages 17ff Another adjust ment which becomes obvious only after a latent period 15 the increase in blood volume For example a patient may show evidences of an acute decrease in cardiac output at the onset of an attack of paroxysmal auricular tachycardia but does not have obvious venous congestion Venous con gestion may develop if the attach persists for hours or days and during this period the blood volume becomes elevated (10) The rise in blood volume may be too rapid to be at tributed to increased activity of the blood forming organs ·FAILURE OF THE HEART 83 but can be explained readily on the basis of retention of salt and water by the kidney ACUTE FAILURE OF THE LEFT VENTRICLE The chain of events seen in acute left ventricular failure stems from the decrease in left ventricular output The de crease in output results in a decrease in the pressure and volume of blood in the arterial tree and this in turn re sults in the changes diagrammed under decreased arterial blood pressure in Figure 7 In fact the pattern in the systemic arterial tree in acute left ventricular failure is not unlike that in hemorrhagic shock on the other hand unlike shock the central venous pressure and volume of blood in the pul monary circuit is not decreased Typically it is increased Systemic arteriolar constriction is elicited by both humoral and nervous mechanisms the humoral mechanisms being activated largely by the disproportionately great decrease in renal blood flow (106 107 112) If cardiac output remains low the blood volume becomes elevated as the characteristic syndrome of chronic left ventricular failure develops The differences between acute left ventricular failure and acute combined right and left ventricular failure (when not superimposed on chronic failure) are not strik ing In the former case the right ventricle is responding more normally to its venous return than the left ventricle 50 that the fraction of the total blood volume which is con tained in the pulmonary circuit will be increased The pul monary venous pressure will be elevated and the systemic venous pressure will be within the upper limits of the normal range or mildly elevated CHRONIC FAILURE OF THE LEFT VENTRICLE If the left ventricular output is chronically lowered and a rise in blood volume occurs both pulmonary and sys temic venous pressure may be expected to rise further ·34 HEMODYNAMICS IN FAILURE OF CIRCULATION following any further decline in left ventricular output so that the systemic venous pressure is elevated even though the right ventricle is capable of responding normally to the venous pressure In this circumstance the right ventri cle is responding to the elevated systemic venous pressure with a more forcible contraction which serves to maintain flow through the pulmonary circuit into the left atrium in spite of the elevated pressure The left ventricle which is in failure in turn may respond to the elevated pulmonary venous pressure with a near normal output RIGHT VENTRICULAR FAILURE IN THE PRESENCE OF LEFT VENTRICULAR FAILURE Whenever the right ventricle fails subsequent to left ventricular failure a rise in systemic venous pressure is to be expected pulmonary venous pressure may de crease for a time but will remain above the normal level The mechanism is considered to be as follows As stated above the output of the left ventricle in failure is being maintained through the stimulus of elevated pulmonary venous pressure for which the right ventricle is responsible When the right ventricle fails the filling pressure for the left ventricle decreases and cardiac output falls With ? fall in pressure in the systemic arterial tree there is also a fall in volume this volume being transferred to the systemic veins and thus producing a further elevation in systemic venous pressure If the systemic veins are only moderately filled as in acute left ventricular failure the transfer of blood associated with failure of the right ventri cle will produce less of a rise in pressure than when it fails in the presence of chronic left ventricular failure In the latter case elevated blood volume as well as redistribu tion of blood is contributing to venous engorgement and further redistribution toward the venous side incident to ·FAILURE OF THE HEART 35 further decrease in left ventricular output would be ex pected to produce a considerable rise in venous pressure ACUTE FAILURE OF THE RIGHT VENTRICLE Experimentally acute and chronic impairment of the pumping action of the right ventricle has been produced by destruction of the tricuspid valves (90) by occlusion of all the major arteries supplying the right ventricle (70 162) and by cauterizing the right ventricular musculature (162) In acute experiments the right ventricle has been completely by passed for short periods by methods which also impair the coronary circulation (139 189) Such procedures when the remainder of the cardiovascular system is normal are compatible with the life of the animal The venous pressure is within normal limits or mildly elevated These results are not difficult to understand when the pressures in the various parts of the cardiovascular system illustrated in Figure 4 are considered The mean pressure in the pulmonary artery under normal conditions is only 15 17 mm Hg and a central venous pressure around 20 cm of water would be sufficient to maintain blood flow through the lungs in the absence of any pumping action of the right ventricle CHRONIC FAILURE OF THE RIGHT VENTRICLE In chronic weakness of the right ventricle as the only de fect in the cardiovascular system one would expect that the systemic venous pressure might become elevated to a level sufficient to perfuse the lungs This rise in venous pressure would be produced by the mechanisms elicited by decreased left ventricular output The level reached would not need to be as high as that commonly seen in chronic congestive heart failure with edema and one would not expect that severe chronic congestive heart failure would develop even ·36 HEMODYNAMICS IN FAILURE OF CIRCULATION though the right ventricle be non functioning as a pump ing chamber Chronic experiments which serie to clarify this problem include destruction of the tricuspid valve (90) which per mits the right ventricle to pump a large portion of its con tents back into the systemic venous system and infarction of the right ventricular musculature by ligation of the arteries carrying its blood supply (70 162) Dogs may re cover from these surgical procedures and live for a pro longed period without developing venous congestion Al though it may be objected that in these experiments the pumping action of the right ventricle has not been com pletely eliminated it does seem likely that complete inacti vation of the right ventricle when the left ventricle is in tact and resistance in the pulmonary circuit is normal would not result in venous congestion of the degree com monly seen in chronic congestive heart failure Now the background has been established for discussion of true chronic congestive heart failure as an entity The cardiovascular adjustments will be described basic causes will be classified and the mechanism of the rise in blood volume will be discussed TRUE CHRONIC CONGESTIVE HEART FAILURE Cardiovascular Adjustments in chronic congestive heart failure there is an increase in the amount of blood and in pressure in the great veins As failure progresses there is a gain in weight disproportionate to the caloric intake and eventually there may be edema in the lungs or in the dependant parts of the body or both The lesions which lead to chronic congestive heart failure are present prior to the development of the characteristic features of the syndrome The pathologic physiology of this preconges tive phase has been the subject of numerous investigations and the following facts have been demonstrated The degree ·TAILURE OF THE HEART 37 of increase in the cardiac output in response to a stand ard exercise test is less than normal (2 69 97 109 114) the time required for the oxygen consumption to return to the basal level is longer than normal (114) and the increase in cardiac output which is elicited by increasing the venous pressure as by venous infusions or by changes in posture 18 less than normal (97) At this early stage the cardiac out put under basal conditions may be within the normal range on the other hand the output does not increase under stress to the levels which are attained in normal subjects An increase in the venous pressure when the patient is at rest occurs at a relatively advanced stage in the development of congestive heart failure Even at this stage the cardiac output may be within the normal range for the oxygen requirement of the patient the decompen sated heart is maintaining a normal output in the presence of and possibly in response to an elevated venous pressure (97) As the decompensation becomes more severe the venous pressure becomes further elevated and a stage is finally reached in which the cardiac output is considerably reduced even though the enous pressure is quite elevated In the most severe forms the enous pressure is elevated to the point of overdistending the ventricle so that cardiac output actually may be reduced as a consequence of the excessive venous pressure (99) From these facts it would seem that in both the pre-congestive and the congestive phase a failing ventricle is one which does not respond to a given venous pressure with an output as great as that of the normal ventricle The pressure-output curve is displaced downward as illustrated in Figure 2 An increase in blood volume is a consistent finding in chronic congestive heart failure except in certain stages in which the venous pressure may be maintained through increased extra vascular support of the walls of the veins (123) Increased venous pressure is brought about in part ·38 HEMODYNAMICS IN FAILURE OF CIRCULATION through the increase in blood volume and these changes in blood volume and venous pressure may be viewed as com pensatory in that the heart is stimulated to maintain a normal or more nearly normal output In short there are three prominent and reasonably con sistent basic findings in true chronic congestive heart failure as defined above I) subnormal increase in cardiac output in response to a given increase in venous pressure 2) elevated venous pressure and 3) increased blood volume The increased blood volume in the presence of a sustained arteriolar tonus contributes to the elevation of the venous pressure and this in turn may stimulate the heart to main tain an output within the normal range with the patient at rest During exercise the output typically does not in crease to the extent that it increases in normal subjects Basic Causes If chronic congestive heart failure is to in clude by definition only those cases in which there is im pairment of transfer of blood and since the transfer in the final analysis is dependent on the left ventricle the causes of chronic congestive heart failure may be classified under three headings 1) Hypodynamic left ventricle 2) Inter ference with filling of the left ventricle and 3) Inefficient left ventricle The left ventricle may be hypodynamic that is lack the force to pump blood because of 1) involvement of the left ventricular musculature from infarction fibrosis de ficiency of metabolites toxins etc and 2) excessively fast rates etc The mechanisms for elevation of venous pressure in such cases are as already described for a sustained decrease in left ventricular output ie there is redistribution of blood toward the venous side and a more or less gradual in crease in blood volume Output may approach normal through the stimulation of the left ventricle by an elevated pressure in the pulmonary circuit or it may be low esen though the venous pressure is elevated or when the filling ·FAILURE OF THE HEART 39 pressure is excessite the overdistention of the ventricle may cause a further decrease in output In the latter case it is pos sible that improved cardiac output may be obtained by vene section but in cases in which this level of pressure has not been reached venesection would be expected to cause a decrease in cardiac output In chronic congestive failure occurring because of a hypodynamic left ventricle both pul monary and systemic venous pressure may be elevated but the rise in pulmonary venous pressure is greater since the left ventricular output is maintained at the level of the right ventricular output only when the left ventricle fills under a higher head of pressure When the right ventricle fails subsequent chronic left ventricular failure as a consequence of chronic changes incident to pumping against an elevated pressure pressure in the pulmonary circuit falls therefore left ventricular filling and conse quently left ventricular output decreases and there is a further increase in systemic venous pressure In summary a hypodynamic left ventricle will cause an increase in volume and an increase in pressure in the pulmonary circuit and in the systemic veins but the en gorgement is more prominent in the pulmonary vascular bed When the right venırıcle fails also a fall in pulmo nary pressure and in left ventricular output results and there is a further rise in systemic venous pressure There are a number of lesions which may be grouped to gether in that they interfere with left ventricular filling so that a normal or subnormal filling occurs in the pres ence of an elevated venous pressure These may be sub divided into those characterized by I) Obstruction to flow of blood or bachflow at the tricuspid valve 2) Obstruction to the flow of blood at the pulmonic valve or in the pulmo nary circuit or at the mitral valve typically combined with failure of the right venificle and 3) Interference with left ventricular filling by compression of the heart ·10 HEMODYNAMICS IN FAILURF OF CIRCULATION from without The hemodynamics must be considered separately in each of these three types 1 In tricuspid stenosis or insufficiency the filling or the output of the right ventricle is maintained through an elevated venous pressure The rise in venous pressure may be visualized as occurring as follows As the stenosis de elops it would tend to decrease right ventricular filling consequently left ventricular filling and output would not be maintained Decreased left ventricular output would result in increased venous pressure by the mecha nisms already described The rise in systemic venous pres sure would tend to restore right ventricular filling to normal In tricuspid insufficiency an increased filling in cident to an elevated venous pressure results in an in creased stroke volume through Starling s law so that the net output of the right ventricle is maintained even though some of the blood is pumped back through the tricuspid valve Therefore a normal flow of blood to the left ventri cle is maintained 2 When there is obstruction to flow of blood in the pulmonary circuit or at the mitral valve the right ventri cle through Starling s law responds to the increased re sistance to outflow with increased strength of contraction and may maintain a normal output and hence normal filling of the left ventricle This is analogous to the main tenance of a normal output by the left ventricle against greatly elevated systemic arterial blood pressure If the riglit ventricle fails then left ventricular filling and out put are not maintained When this occurs the venous pres sure rises as in any case where left ventricular output de creases 3 In cardiac compression a situation is encountered in which there is elevated senous pressure serving to maintain normal or even subnormal filling Stroke volume is low and the tendency for the output and arterial blood pres.

·FAILURE OF THE HEART 41 sure to fall is opposed by reflex cardiac acceleration As the condition becomes more severe the left ventricular output is not maintuned and consequently the venous pressure rises The left ventricle may be said to be inefficient in those conditions in which it must re pump blood 1e mitral or aortic regurgitation In either case the net output is less than the actual left ventricular output Reflling from the aorta during diastole will through Starling s law stimulate a stronger contraction which may compensate for the amount of blood which regurgitates If left ventricular output is not maintained venous pressure will become elevated by the mechanisms already described In mitral insufficiency the net left ventricular output tends to be te duced with the consequent rise in venous pressure and restoration of a near normal output Blood Volume An increase in venous pressure is an integral part of the syndrome of chronic congestive heart failure In an elastic system an increase in pressure is pro duced when the holding capacity of the system is de creased or when the fluid content is increased Active arte riolar constriction and venoconstriction are possible mecha nisms for decreasing the holding capacity of the cardiovascu lar system Normally the venous system is only partially filled with blood and a considerable decrease in holding capacity of the cardiovascular system incident to contraction of smooth muscle in the vascular tree promotes filling of the large veins but does not cause an increase in venous pres sure of the magnitude seen in congestive failure It is true however that after the extra-cellular fluid has reached high levels in chronic congestiye failure there may be enough additional extra vascular support to maintain a high venous pressure with little increase in intra vascular volume (159) It seems 1s Starr lias said (162) that the simplest ex planation for the increase in venous pressure is that it ·42 HEMODYNAMICS IN FAILURE OF CIRCULATION is produced in considerable part by an increase in blood volume Many investigators have measured the blood volume in patients with congestive failure Altschule (2) summarized the work in this field prior to 1938 and found general agreement that there is a significant rise in blood volume during the course of chronic congestive heart failure Gibson and Evans (55) showed an increased blood volume and demonstrated a direct correlation between the degree of increase in blood volume and the severity of the symptoms Seymour Pritchard Langley and Hayman (150) found an average increase of 25% in blood volume The majority of the measurements have been made using the dye methods particularly Evans blue Various objections to the dye methods recently have been discussed by Peters (123) and by Nylin and Hedlund (117) Starr s studies con cerning the venous pressure in patients with and without congestive failure both in life and after death were de scribed on page 14 The increase in the static blood pressure is presumptive evidence of an increased blood volume Several investigators (116 125 148 172) using the carbon monoxide method have found a significant in crease in blood volume during decompensation The blood volume was decreased following digitalization Nylın (116) and Nylin and Hedlund (117) in measuring the erythrocyte volume and the whole blood volume by means of radioactive phosphorus found that both were increased during decompensation As compensation was restored the blood volume fell 28% and the erythrocyte volume fell 18% It has been suggested repeatedly that the peripheral hypoxia which is found in congestive failure stimulates production of erythrocytes the blood volume increasing secondarily However oxygen lack does not cause as rapid or as great an increase in blood volume as occurs in some cases of congestive failure Moreover in the early stages ·FAILURE OF THE HEART 43 of failure the change is in the direction of hemodilution rather than hemoconcentration (122 150 178) However it is possible that hypoxia is concerned with stimulating the bone marrow to maintain the hematocrit at normal levels in the presence of a chronic increase in plasma Volume The information available at present indicates that the rise in blood volume in patients with true chronic congestive failure is related to retention of salt and hence of water by the kidney secondary to reduced renal blood flow Changes in renal function in patients with heart failure are summarized below i Renal blood flow as determined by para amino-hippurate clearance is markedly reduced in the patients with congestive failure who have a significantly decreased cardiac output (106 109 111 150 183) Morcover the per cent reduction in renal blood flow greatly exceeds the per cent reduction in cardiac output (106 111) 2 Glomerulor filtration as shown by inulin or man nicol clearance is decreased in patients having a decreased cardiac output but it is not decreased as markedly as renal blood flow ie the filtration fraction is increased Mokotoff Ross and Leiter (111) in 16 patients found a filtration fraction twice normal in the presence of a renal blood flow of one third normal 3 Urinary sodium excretion is decreased Futcher and and Schroeder (52) determined the increase in sodium excretion after adding a given amount to the basal intake and found that in patients with congestive failure it was less than 30% of normal Reaser and Burch (129) using radioactive sodium reported that a normal control subject excreted ninety times as much sodium as a decompensating patient on the same salt intake Threefoot Gibbons and Burch (181) showed that patients while decompensating excreted less sodium than the controls and while recom ·44 HEMODYNAMICS IN FAILURE OF CIRCULATION pensating excreted more sodium than the controls Numer ous other papers in which a reduced sodium excretion has been found in patients with congestive failure are indı cated in the key to the bibliography 4 Tubular reabsorption of sodium is not impaired It is normal or increased Mokotoff (111) found that the mean cubular reabsorption was the same per 100 cc of glo merular filtrate in patients with or without heart failure Other investigators maintain that under certain conditions sodium absorption is increased 5 IVater excretion as measured by the diuretic response to drinking water is relatively unimpaired On a dietary salt intake of one gram per day water diuresis occurs as completely in the cardiac as in the normal subject Ade quate studies have been made by Schemm (145 146) and many others (17 57 88 89 147 194) showing the im portance of restricting salt and the advantages of allowing fluids ad lib in patients with congestive heart failure The alterations in renal function described above show no correlation with the venous pressure per se However there seems to be 1 definite correlation with the adequacy of the cardiac output Whenever the cardiac output drops below that which is required to satisfy the metabolic needs of the body there is an immediate change in renal func tions The primary change in renal function incident to decreased renal blood flow is the retention of sodium and secondarily the retention of water Thıs tends to increase the intravascular and interstitial fluid volume and there fore venous pressure An elevated venous pressure will cause increased filling of the ventricle and consequently through Starling s law will tend to restore cardiac output to the normal range During this stage as mentioned by Peters (123) a transfusion may help to restore a normal output and phlebotomy may cause an acute decrease in output Renal retention of salt and water is only one of ·FAILURE OF THE HEART 45 several mechanisms which are operating simultaneously at least in the acute stages all tending to maintain cardiac output The dernonstration of a decrease in renal blood flow and an increase in the filtration fraction in patients with con gestive failure points toward constriction of the efferent arterioles of the kidney (106) This constriction appears to be independent of the nervous pathways to the kidney (112 183) and perhaps is caused by the same humoral mechanisms which help to maintain the continued general arteriolar constriction characteristic of chronic congestive failure A search is under way for the humoral basis for the changes Merrill (110) has found renin in the renal vein of patients in failure suggesting angiotonin as a mediator of the arteriolar constriction A role of adrenal steroid hormones has been suggested and it is known that over dosage with desoxycorticosterone will produce the clinical picture of congestive heart failure (50 95 179) Further work is necessary before the exact mechanisms by means of which an insufficient cardiac output causes renal reten tion of salt and water can be described A detailed hypothesis has been presented by Wesson Anslow and Smith (193) ·--4- CHRONIC VENOUS CONGESTION WITHOUT HEART FAILURE we DIFFERENTIATION FROM TRUE CONGESTIVE HEART FAILURE IN PRECEDING sections have described the development of venous congestion fol lowing more or less obvious defects in or interference with the transport of blood in the cardiovascular system In these conditions the cardiac output is either normal or decreased when considered in relation to the oxygen con sumption There are other chronic conditions in which venous pressure and blood volume are elevated the heart is en larged and edema may develop yet the cardiac output is elevated above the normal range The best example of this combination of findings is seen in the early and intermediate stages of beriberı There is a similar picture but to a lesser degree in some cases of systemic arteriovenous fistula These conditions are not related to interference with the transport of blood in fact the resistance to flow in the systemic circuit is decreased in each case Also in hyperthyroidism cardiac output may be above the range for normals but is not in creased when considered in relation to the oxygen require ment When true heart failure occurs in hyperthyroid patients as in any case of failure the venous pressure is elevated and the ratio of cardiac output to oxygen consump tion is normal or decreased Attempts to discuss the pathologic physiology of the conditions not associated with defective transport of blood in the same category with conditions which are character 46 ·CHIROVIC CONGESTION-HEART FAILURF 47 ized by defective transport lead to confusion concerning the mechanisms involved in congestive heart failure The initial change in the cardiovascular system differs in the two groups of conditions in Irue congestive failure defec tive transport leads to increased blood volume in the other group increased blood volume occurs on some basis other than defective transport, and the heart is stimulated to a higher than normal output The latter syndrome may be alled chronic venous congestion without failure If chronic venous congestion becomes sufficiently severe then a decrease in cardiac output may occur from over distention of the ventricles The difference between these tho syndromes both as to basic mechanisins concerned and efficacy of methods of treatnent is generally recognized and a subdivision into these two categories is commonly made tacitly if not ac tually For example Wood and Paulett (199) say Effect of digoxin on the venous pressure or right atrial pressure was measured in four cases of classical congestive heart failure and in 12 with venous pressure raised for other In the four examples of congestive heart failure the venous pressure or right auricular pressure fell con spicuously within 30 minutes and the cardiac output when measured rose In the twelve patients without congestive heart failure the right auricular pressure did not alter appreciably within 40 minutes The cardiac output when measured was either unchanged or fell with the pulse rate Chronic venous congestion without failure includes by the above definition all conditions in which venous con gestion is secondary to an increase in blood volume occur ring on a basis other than a defect in the transport of blood In these conditions the arteriolar tonus is sustained well enough so that the excess volume is contained largely in reasons ·48 HEMODYNAMICS IN FAILURE OF CIRCULATION the venous system and cardiac chambers rather than in the systemic capillary bed Such conditions should not be re ferred to as heart failure since there is no weakness of the heart demonstrable by the tests we now have (160) The heart is responding with increased output and increased work as a normal heart would be expected to respond under the same stimuli EXAMPLES OF THE SYNDROME Chronic venous congestion without failure definitely occurs in certain stages of beriberi and apparently occurs in some cases with arteriovenous fistula possibly it may occur in certain stages of desoxycorticosterone overdosage in patients with adrenal cortical insufficiency Experimen tally venous congestion can be produced by excessive blood transfusion alone or by transfusion plus adminis tration of vasoconstrictor compounds or in some species by overdosage with vasoconstrictor compounds in the pres ence of a normal blood volume When the rise in venous pressure incident to the rise in volume in the venous system is mild or moderate venous congestion without failure is produced but when the venous pressure is ele vated excessively the ventricles become overdistended so that cardiac output decreases When a decrease in cardiac output occurs as a result of severe venous congestion further flow of blood to the venous side would occur as arterial pressure decreases and the deleterious effects of this transfer would be great since the venous system is already overfilled Various diseases and some methods of management of patients lead to an increase in blood volume and second arily to chronic venous congestion in the absence of car diac weakness At present it is not possible to list all of the diseases concerned or all of the mechanisms by means ·CHROVIC CONGESTION--HEART FAILURE 49 of which the blood volume may become increased The hemodynamics in arteriosenous shunt and in beriberi will be described here briefly to introduce the problem and to compare and contrast this syndrome with true chronic congestive heart failure Systemic Arteriovenous Fistula Arteriovenous fistula does not always lead to venous congestion and does not provide the best example of the syndrome but it is most instructive to consider it first since in this case there 18 a single and evident defect leading to the development of the final complex pattern of findings In arteriovenous fistula the resistance to flow of blood from arteries to veins is decreased in proportion to the size of the fistula All other deviations from normal must stem from this initial change In the one-circuit model illustrated in Figure 5 this situation may be simulated by opening the clamp which determines the resistance to flow from the arterial to the venous side If only this change is made the pump output and fluid volume remaining constant a certain volume of fluid is transferred from the arterial side to the venous side so that a new equilibrium is established at ? higher level of venous pressure and a lower level of arterial pressure The rise in pressure on the venous side is con siderably less than the fall on the arterial side since the Venous side is relatively less filled and is more distensible However in the experimental animal when an arteriove nous fistula is opened not only is the peripheral resistance decreased as in the model there is also an increase in the volume of blood retained in the veins and capillary beds peripheral to the fistula This constitutes a decrease in the volume of blood returning to the right atrium and hence available for circulation Thus to simulate in the one Circuit model the conditions on the arterial and venous side in an arteriovenous fistula it is necessary not only to ·50 HEMODYNAMICS IN FAILURE OF CIRCULATION reduce the peripheral resistance but also to withdraw som blood from the system The reduction in volume will de crease or neutralize the rise in venous pressure inciden to decreased peripheral resistance The changes produced by opening and closing an ar teriovenous fistula in man or experimental animals may N FICURE 9 Schema of a systemic arteriozenous fistula Compare with Figure 3 N refers to the fraction of the cardiac output flowing through normal channels $* refers to the fraction flowing through the shunt be emphasized by considering the systemic blood flow in two parts S being that which flows through the shunt and N being that which flows through the normal channels This is illustrated in Figure 9 In the presence of a given head of pressure in the arterial tree N and S will be deter mined by the respective resistances in the two paths that the blood can take As the shunt is closed pressure in the entire arterial tree is elevated and flow in N is increased ·CHROVIC CONGESTION-JIEART FAILURE 51 When the shunt is opened the reverse occurs It is obvious that opening a large arteriovenous fistula will cause a decrease in the blood flow in the artery beyond the shunt it is also true that it will decrease the flow in the arteries which are not anatomically involved For example open ing a large arteriovenous fistula eg between the iliac ar tery and vein will result in a decreased renal blood flow both by lowering the head of pressure in the renal artery and by eliciting reflex constriction of renal arterioles Holman (71) lists as follows the changes produced by establishing an arteriovenous fistula in the experimental animal The immediate changes due to the establishment of a fistula are 1 A fall in general arterial blood pressure affecting both systolic and diastolic levels 2 An increase in pulse rate 3 An increase in venous pressure proximal as well as distal to the fistula which is slight or pronounced according to the size of the fistula 4 An increase in cardiac output depending upon the size and location of the fistula 5 A very temporary decrease in the size of the heart and of the artery proximal to the fistula due to the sudden diversion of blood from the arterial into the capacious venous system an alteration comparable to that seen in massive hemorrhage The more remote effects following the introduction of fistula are 1 A permanent diversion of part of the circulating blood from the normal capillary bed into the fistulous circuit 2 A gradually increasing total blood volume pro -- ·52 HEMODYNAMICS IN FAILURE OF CIRCULATION ceeding pari passu with the amount of blood diverted through the fistula 3 A gradual dilatation of the heart and of the artery and vein proximal to the fistula due to the dis tending effect of an increased olume or bulk of blood attracted to the fistulous circuit because of its lessened resistance 4 The development of an extensive collateral ar culation due to the lowered resistance to the flow of blood at the site of the fistula In the presence of a constriction of the artery proximal to the fistula a comparatively rare occurrence clinically this exten sive collateral circulation pours blood into the artery distal to the fistula thus causing a dilatation of the artery to occur distal to the fistula instead of proximal to it 5 Slight hypertrophy of the heart due partly to dilatation and overdistention and partly to the in creased work necessary to propel forward the increasing volume of blood flowing through at The enlargement of the heart is due mainly to a dilatation and only to a very minor degree to hypertrophy 6 A gradual recovery from the lowered blood pres sure noted immediately after the formation of the fistula the systolic being equal or higher the diastolic definitely lower than that existing before the forma tion of the fistula thus producing a greatly increased pulse pressure Holman s view of the problem and his recognition of the relationship between this and quite different causes of ienous congestion are esident from these statements in Bus introduction A direct communication between the ar terial and venous systems is a unique lesion that illus ·CHRONIC CONGESTION-HEART FAILURE 53 trates as no other lesion can certain physiological con cepts of fundamental importance in the understanding of both the acquired and congenital disorders of the air culatory system Under no other circumstances for example 15 it possible to produce such a startling increase in general blood pressure as may be produced by the simple expedi ent of closing a large peripheral fistula In seeking an explanation for this phenomenon it was necessary to in troduce a new concept namely an increase in the total volume of circulating blood as a compensatory reaction to the altered hydrodynamics of the circulation resulting from the fistula It is probable that this same concept of an increase in total blood volume is applicable in the ex planation of some of the circulatory phenomena attending such cardiac disorders as incompetent valves and congeni tal malformations In the years since Holman s monograph it has become increasingly evident that various conditions resulting in a chronic decrease in renal blood flow promote an increase in the blood volume possibly through the retention of salt and as diagrammed in Figure 10 this is probably the mechanism for the increased blood volume in arterio Yenous fistula The immediate compensatory mechanisms acting in arteriovenous shunt are mainly those which are associated with the decrease in arterial pressure Cardiac output is increased but apparently not to a level sufficient to restore capillary blood flow to normal Later blood volume in creases and it is probable that this serves as an additional stimulus through restoration or even elevation of right atrial pressure (26) to increase the cardiac output so that adequate capillary blood flow is maintained in spite of the loss across the shunt Holman (71) states that the extent of the increase in total blood volume depends upon the size ·54 HEMODYNAMICS IN PAILURE OF CIRCULATION Opening a large arterio venous fistule. Decreased resistance to arterial outflow Decreased arterial blood pressure Carotid sinus and tortic arch reflexes elicited Renal Erteriolar construction Decrcscd Tenal blood flow Generalized vasoconstriction r24 Increased blood volume Increased heart Tote たいにお increased right atrial Pressure Increased strength increased Cardiac of cardiac output cantraction --- FIGURE 10 Basis for de elopment of the changes in the cardior ascular sys tem following the opening of a large art riot enous fistula Acute adjust ments are indicated in solid line bores the more chronic changes in broken line boxes of the fistula After operative removal of a large arteriovenous fistula there is typically a considerable decrease in blood volume amounting to as much as 1000 cc (41) per square meter of body surface Beriberi A consistent pattern of cardiovascular changes ·CHRONIC CONGESTION-HEART FAILURE 55 Is seen in patients suffering from severe deficiency of thiamine (6 23 126) As in patients with true congestive failure there is increased heart size increased venous pressure increased blood volume and there may be edema Unlike the cases with true failure (defective transport of blood) the cardiac output is greatly elevated even when con sidered in relation to the oxygen consumption which is also elevated circulation time and arterios enous oxygen differ ence are decreased rather than increased The abnormal cardiovascular pattern develops from thiamine deficiency and is slowly reversible when thiamine is administered Porter and Downs (126) carefully studied the circula tion in two patients with severe beriberi They state Our observations bear out those of others that during conges tive heart failure associated with vitamin B deficiency there may be an increased cardiac output a low arteriovenous oxygen difference an elevated venous pressure and a shortened circulation time During recovery there is a change toward normal of these measurable circulatory phenomena viz a decline in cardiac output an increase in the arteriovenous oxygen difference a fall in venous pressure and a prolongation of the circulation time In addition in the one patient studied it was shown that during failure there was a marked increase in the plasma and total blood volume both of which returned to normal during recovery They further state We also found in both patients an initially high oxygen consumption which likewise gradually returned to normal under observation It may be argued that this high oxygen consumption ac counted for the high cardiac output values but the fact that the arteriovenous difference was abnormally low indi cates that the cardiac output was increased out of proportion to the metabolic needs of the body Roentgen rays of the heart shadow in both cases showed the dimensions ·56 HEMODYNAMICS IN FAILURE OF CIRCULATION considerably increased beyond normal before therapy Be ginning a few days after the start of therapy there was a progressive decrease in the size of the heart shadows which gradually returned to normal limits within two weeks The electrocardiograms in both patients revealed essentially normal complexes at the beginning of observation and no definite change following therapy The study by Burwell and Dexter (23) by newer techniques 18 in agreement with that of Porter and Downs (126) on essential points In this syndrome as Starr has commented (23) the heart behaves as if it is stimulated rather than as if it is weak What thes is the source of the stimulanon? It is probable that a metabolic defect incident to chronic thuamine de ficiency causes vasodilatation This would result in reflex cardiac stimulation Also in the presence of generalized vasodilatation the resistance to flow in the kidney where re sistance is already low is not decreased as much as in other vascular beds This results in a decrease in renal blood for until compensated by in increased cardiac output Thus one may speculate that in beriberi a decrease in renal blood flow may provide the basis for the rise in blood volume which would serve as a further stimulus to the heart Weiss and Will ins (192) state that arteriolar constric tron following B, therapy must also react in turn centrally on the heart in the same beneficial manner as the closing of an arteriovenous aneurysil It is quite possible that the inwal defect in the cardiovascular system in these two conditions is the same se a decreased peripheral resist ance and hence the sequence of events depicted in Figure 10 also may apply to beriberi On the other hand path ologic material indicates that the myocardium may be damaged in the later stages of beriberi In any case in either beriberı or arteriovenous shunt it is to be expected ·CHRONIC CONGESTION-HEART FAILURE 57 that a decrease in cardiac output from the abnormally high level will develop if the blood volume and venous pressure become excessive so that the ventricles are over distended An understanding of what has led to a rise in blood vol ume and chronic venous congestion in the individual case is necessary before the correct treatment can be instituted If the heart is weak and the cardiac output is normal or low the value of digitalis and related compounds as an adjunct to various other measures as well established If the heart is not weak and the output is high digitalis alone will be relatively ineffective or even detrimental specific therapy determined by the etiology of the disease is neces sary along with other measures which influence the blood volume ·BIBLIOGRAPHY KEY TO PRINCIPAL SUBJECTS* General or interpretative articles 2 9 33 46 56 65 102 121 123 130 139 134 136 155 158 160 165 166 178 196 Books and monographs 39 51 62 82 182 Cardiac output 31 44 59 64 73 97 104 114 133 150 157 161 166 168 169 171 173 174 175 Relation of cardiac output to renal function 10 11 18 19 20 21 28 88 106 109 111 124 149 150 183 193 195 Sodium excretion 52 58 78 79 88 107 111 129 154 181 193 Sodium restriction 17 22 57 88 89 129 130 145 146 147 191 Venous pressure 25 53 54 55 83 84 159 161 181 188 197 199 Pressures in the right heart and lesser circulation 7 16 31 61 66 87 99 135 137 170 171 Blood volume 54 55 84 105 116 117 125 150 159 164 188 198 Renın angiotonin and other vasotrophic substances 14 24 34 60 76 110 120 153 Effect of cardiac glycosides 8 36 81 101 103 163 170 173 191 199 Arteriovenous fistula 26 35 41 63 71 72 128 131 Circulation in beriberi 1 6 23 42 126 176 190 192 I AALSMEER WC and WENCKER4CH K F Herz und Kreislauf bei der Beri beri Krankheit Ilien Arch finn Med 16 193 272 1999 2 ALTSCHULE M D The pathological physiology of chronic cardiac decompensation Medicine 1775 154 1938 3 ALTSCHULE M D and GILLIGAN DR The effects on the cardio vascular system of fluids administered intravenously in man 11 The dynamics of the circulation J Clin Investigation 17 401-411 1938 4 BARACHAL FENN WO FERRIS E B and SaIMIDT CF The physiology of pressure breathing a brief review of its present status J Atiation Med 18-73 87 1947 5 BLAKE W D WEGRIA R KEATINC RP and WARD HP The effect of increased renal venous pressure on renal function Am Physiol 1571 13 1949 6 BLANKENHORN MA The diagnosis of beriberi heart disease Ann Int Med 23 998 404 1915 7 BLOOMFIELD RALAUSON HD COURNAND A BREED ES and RICHARDS D W JR Recording of right heart pressures in normal subjects and in patients with chronic pulmonary disease and vanous • Numbers refer to references which follow 58 ·BIBLIOGRAPHY 59 types of cardioarculatory disease | Clir investigation 5659 661 1916 8 BLOOMFIELD RA RAPOPORT B MELAOL, J P Lonc K. MODE, JG and Eus L. B The effect of the cardiac glycosides upon the dynamics of the arculation in congestive heart failure 1. Ouabain. J Clin Investigation 27-588 599 1948 9 BOLTON C. The pathology of cardiac dropsy Brit ated 1612-616 1917 10 BORST J G G The maintenance of an adequate ardiac output by the regulation of the urinary exaction of water and sodium chlonde an essential factor in the genesis of oedema Adla med Scandinav Supplement CCVII (207) 130 1918 11 BRADLEY S E and BLAKE 1 D Pathogenesis of renal dysfunction during congestive heart failure Am J Aled 64,0-480 1919 12 BRADLEY S E. and BRADLEY GP The effect of increased intra abdominal pressure on renal function in man J Clin Investigation 26 1010 1022 19 17 13 Budur S E and BRADLEY G P.. Renal function during chronic anemia in man, Blood 2 192 207 1917 14 BRADLEY S E. and PARKER B The hemodynamic effects of angiotonin in normal man Clin Investigation 20715 719 1911 15 BRAMLAMP R C The protein content of subcutaneous edema fluid in heart disease J Clin Investigation 14 31 36 1935 16 BRANNON ES MERRILL, A WARREY J V and STEAD E. A Ju. The cardiac output in patients with chronic anemia as meas ured by the technique of right atrial catheterization J Clin In vestigation 24 332 336 1915 17 Bridges W C WHEELER E O and WHITE P D Low sodium diet and free fluid intake in the treatment of congestive failure New England J Med 234 573 578 1946 18 Baicos A.P FOWELL, D M HAMILTON W F REMINGTON J W WHEELER N C. and WINSLOW JA Renal and arculatory factors In the edema formation of congestive heart failure j chn In vestigation 27 810 817 1918 19 BRUNC KNUDSEN E OE and RAASCHOU F The influence of posture on the kidney function The fall of the diuresis in the erect posture Acta med Scandinav 122 315 331 1945 20 BRUN C KNUDSEN E O E and RAASCHOU F On the cause of postsyncopal oliguria Acta med Scandinav 122 486 500 1915 21 BRUNC KNUDSEN EO E and RAASCHOU F Kidney function and circulatory collapse post syncopal oliguria J Clin Investiga 1107 23 568 574 1946 22 BURCH G and REASER P Water and sodium balance in congestive heart fallure New Orleans MSI 99 124 128 1916 ·BIBLIOGRAPHY KEY TO PRINCIPAL SUBJECTS* General or interpretativt articles 2 9 33 46 56 65 109 121 129 130 137 134 336 155 158 160 165 366 378 196 Books and monographs 19 51 62 8? 182 Cardiac output 31 44 59 64 73 97 104 114 113 150 151 161 166 168 169 171 173 174 15 Relation of cardiac ourput to renal function 10 11 18 19 20 21 28 86 106 109 111 24 149 350 185 195 195 Sodium excretion 59 58 78 79 88 307 113 129 35+ 181 193 Sodium restrsction 17 22 37 88 89 129 130 145 146 147 394 Venous pressure 25 53 54 55 B3 81 159 164 183 188 197 199 Pressures in the right heart and lesser circulation 7 16 31 61 66 87 94 135 357 170 171 Blood volume 54 55 84 205 116 117 125 150 159 161 IBB 198 Rensa anglotonin and other vasoprophic substances 34 21 34 60 76 110 120 353 Effect of cardiac glycosides 8 36 81 101 103 169 170 173 191 199 Artcriocnous fistula 26 35 43 63 71 72 128 131 Curculation in berbeni 1 6 23 42 926 176 190 192 I AALSMEER WC and WENCKERACH KF Ferz und Kreislauf bei der Beri beri krankheit Iften Arch finn bred 16 195 272 399 2 ALTSCHULE VED The pathological physiology of chronic cardiac decompensabon Medicine 1775 154 1938 3 ALTSCHULE MD and GILLIGAN DR The effects on the cardio ascular system of Guds administered intravenously so man !! The dynamics of the circulation , Clin Investigation 17-401-411 3958 # BARACH AL FENN W OFERA E B and Scaturzt CF The physiology of pressure breacking a brief review of its present status ] Autation Med 18 73 87 1917 5 BLAXE W D EGRIA RAEATING RP and IARD HP The effect of increased renal venous pressure on reaal function am I Physiol 1971 13 1919 B BLANKENHORN MA The diagnosis of beriberl heart disease An Int Aled 23 398-404 1945 1 BLOOVTILD RALAUSOY HD COURNAND A BREED ES and RICHARDS D W Jl. Recording of right heart pressures in norma) fubjects and in patients with chronic pulmonary disezse and various • Numbers stler to references which follow 58 ·BIBLIOGRAPHY 61 39 DRND, GK Pulmonary Edema and Inflammation 106 PP Cam bndge Harvard 1915 10 EDHOLM OG HOWARTII S and VcVICHAEL, J Heart failure and bone blood flow in osteitis deformans Clin Sc 5249 260 1915 11 ELIN D C and WARREN) Arteriovenous fistulas their effect on the arculation J.4.14 134 1521 1528 1917 4' EPSTEIN S Observations on beriberi heart disease A Heart I 34 432-410 1917 43 EXCHER D J WY WESTON R. E. LEIVER GLEITER L. and COLDAT $ The effect of aminophylline on cardiac output and renal hemo dynamics in man Federation Proc 7 31 1918 44 ESPERSEN T Studies on the cardiac output and related circulatory functions especially in patients with congestive heart failure Acta med Scandinav 103 153 182 1911 45 ESPERSEN T Congestive heart failure oxygen consumption and lung ventilation Acta med Scandinav 108 183 191 1941 46 FAUX G and ERSHLER I Studies of the factors concerned in edema formation II The hydrostatic pressure in the capillaries during edema formation in right heart failure Ann Int Med 15 99 810 1911 47 FARNSWORTH E B Clearance of inulin diodrast chloride and phos phate under mercunal diuresis Intensive study of a patient in severe cardiac failure Am J Med 1.246 251 1916 48 FARNSWORTH E B Electrolyte partition in patients with edema of various origins Am J Med 4 538 349 1918 49 FARNSWORTH E B and KRAKUSIN J S Electrolyte partition in pa tients with edema of various origins Qualitative and quantitative definition of cations and anions in cardiac decompensat on J Lab Clin Med 33 1734 1544 1948 50 FERREBEE J W REGAN C ATCHLEY DW and LOEB RF Desoxycorticosterone esters JAMA 113 1725 1731 1939 51 FISHBERC A Heart Failure 8 9 Pp Philadelphia I ea 1910 59 FUTCHER P H and SCHROEDER HA Stud es on congesti e heart failure II Impaired renal excretion of sodium chloride Am I Mied Sc 04 52 62 1912 53 GIBBONS T The behavior of the venous pressure during various stages of chronic congestive heart failure Am Heart J 33 553 566 1948 54 Gibson J G JR and Evans W A JR. Clin cal studies of the blood volume II The relation of the plasma and total blood volume to Venous pressure blood velocity rate physical measurements age and sex in ninety normal humans J Clin Investigat on 16 317 3 8 1937 55 IBSON J G Jx and EVANS WA JxCl nical studies of blood vol ·62 HEMODYNAMICS IN FAILURE OF CIRCULATION ume III Changes in blood volume venous pressure and blood Velocity rate in chronic congestive heart failure J Clin Intestiga tion 16 SI 858 1997 56 GOLD H KWIT N T MODEL HANLON LW KRAVER M GREENBERG S Orto HL COTLOVE E W BENTOV J G PLARI. MUTTER M and ZAHN W A system for the routine treatment of the failing heart Am J Afed 3 665 692 1947 57 GORHAM L W LESTER DE WOLF A V and SHULTZ HH The relauve importance of dietary sodium chloride and water intake in cardiac edema Ann Int ved -7 575 583 1917 58 CRANT H and REICH53 IN F The effects of the ingestion of large amounts of sodium chloride on the arterial and venous pressures of normal subjects Am Heart ] 32-701 712 1916 59 CROLLMAN A FRIEDMAN B CLARA G and HARRISON TR Studies in congestive heart failure XXIV A critical study of methods for determining the cardiac output in patients with cardiac disease J Clin Intestigation 12 751 766 1933 60 HAMILTON AS and COLLINS DA Homeostatic role of renal humoral mechanism in hemorrhage and shock Am J Physiol 136 275 284 1912 61 HAMILTON WF WOODEURY RA and VOGT E Differential pres sures in the lesser circulation of the unanesthetized dog Amy Physiol 195 130 141 1939 62 HARRISON TR Failure of the Circulation 502 pp Baltimore Williams and Wilkins 1939 63 HARRISON TR DOCK W and HOLMAN E Experimental studies in arteriovenous fistulae Cardiac output Heart 11 33/ 311 1994 64 HARRISON T R FRIEDMIAN B CLARK G and RESNIK H The cardiac output in relation to cardiac failure Arch Int Afed 54 239 255 1934 65 HARRISON TR REICHSMAN F and GRANT H Some observations on the pathogenesis of cardiac edema Tr A Am Physicians 59 51 52 1916 66 HELLEMS HA HAYNES F1 GOWDEY JF and DEXTER L Pulmonary capillary pressure in man | Clm Investigation 27 510 1918 67 HELLMAN LWESTON RE ESCHER D J 1 and LEITER L The effect of adrenocorticotropin on renal hemodynamics and uric acid clearance Federation Proc 752 1948 68 HEYMANS C BOUCKAERT J J FARBER S and Hsu FY Spinal vaso motor reflexes asociated with variations in blood pressure Am ) Physiol 117 619 625 1936 69 HICKAN J B and CARGILL, W H Effect of exercise on cardiac output and pulmonary arterial pressure in normal persons and in patients ·BIBLIOGRAPHY 63 with cardiovascular disease and pulmonary emphysema J Clin Inzestigation 27 10 23 1948 70 HIL I G # JOLINSON F D and 11 ILSON F N The form of the electrocardiogram in experimental myocardial infarction Am Heart } 16 309 320 1938 71 HOLMAN E. Arteriovenous Aneurysm Abnormal Communication be tween the arterial and Venous Circulations 241 pp New York Macmillan Co 1937 72 HOLMAN E Clinical and experimental observations on arteriovenous fistulae Ann Surg 112 810 878 1910 73 HOWARTA S Vc\ICHAEL J and SHARPEY SCHAFER E P Effects of yenesection in low output heart failure Clin Sc 6 41 50 1916 74 HOWARTH S McMICHAEL, J and SHARPEY SCHAFER E P Effects of oxygen vencsecuon and digitalis in chronic heart failure from dis ease of the langs Clin Sc 6 187 196 1917 7. HOWARTH S Mc\IICHAEL J and SHARPEY SCHAFER EP The arculatory action of theophylline ethylene diamine Clin sc 6 125 135 1917 16 HUIDOBRO F and BRAUN VENENDEZ E The secretion of renın by the intact kidney Am J Physiol 137 47 55 1912 77 JAMES D F TURNER Hand MERRILL A J Circulatory and renal effects of aminophylline in congestive heart failure Am J Ved s 619 1918 78 KATTUS A SINCLAIX SWITX B GENEST J and VEWMAN EV The renal tubular reabsorption of salt with exercise in a patient with cardiac falure and normal controls | Clin Investigation 27 542 1948 19 KATTUS A SINCLAIR SMITH B GENEST J and NEWMAN E V The effect of exercise on the renal techanisms of electrolyte excretion in normal subjects Bull Johns Hopkins Hospital 84 344 368 1949 80 KATZ L N MISE W and JOCHIM K The dynamic alterations in heart failure in the isolated heart and heart lung preparations Am J Physiol 143 507 520 1945 B1 KININMONTH JG The circulation rate in some pathological states with observations on the effect of digitalis Quar!) Med 2 277 296 1928 82 KROCH A The Anatomy and Ph sology of Capillaries 4.2 pp New Haven Yale 1929 83 KROCHIA LANDES E Mand TURNER A H The movement of iud through the human capillary walls in relation to venous pressure and to collo dosmotic pressure of the blood ) Cim Invest gation 11 63 95 1932 81 LAVDJS EM BROWN E. FAUTEUX 4 and WISE C. Central venous pressure in relation to cardiac competence blood volume and exer Cise } Cl Investigation 25-237 235 1916 ·64 HEMODYNAMICS IN FAILURE OF CIRCULATION 85 LANDOWNE MI ALVING AS and ADAMS W Renal and total circulation in two cases of constrictive pericarditus J Clin Invest gation 21 626 627 1942 86 LAUSON HD BRADLEY SE and COURYA'DA The rena) arcula tion in shock J Clin Investigation 23 381 402 1414 87 LAUSON HD BLOOXFITLD RA and COURYAAD A The influence of the respiration on the circulation in man with special reference to pressures in the right aurice right veninde femoral artery and penipheral veins 4m Med 1 315 336 1946 88 LEITER L The role of sodium chloride in the mechanism and treat ment of congestive heart failure Bull Vew York Acad ved 24 702 719 1918 89 LETVY G V STRAZZA J A and AFFIN AF Fluids 10 congestive heart Failure AIA 11 11 11.5 1916 90 LITTLE RC The cardiodynamics of tricuspid insufficiency Proc Soc Exper Biol dared 68 602 603 1948 31 LOEB RI Adrenal cortex and electrolyte behavior Bull New York Acad Ved 18.63 288 19-12 92 LOTSPEICH USD SWAY RC and PITTS RF Renal tabular re absorption of chloride Am} Physiol 148 415-448 1917 93 LYONS RH JACOBSOV S D and AVERY VL Intreases in the plasma volume following the administration of sodiutn salts Am Aled $c 209 148 151 1911 94 I YSHOLA E NYLIY Gand QUAN A The relation between the heart volume and stroke volume under physiological and pathologi cal conditions Acta Radiol 13231 257 1934 95 McCULLACH E. P and RYAN EJ Use of desorycorticosterone acetate in Addison s disease 141A 1117,50 2537 1910 96 MCMASTER P D The lysaphatıcs and lymph flow in the edematous skin of human beings with cardiac and renal disease Exper Bed 65 373 392 1937 97 MCVICITAEL ) Output of heart in congestive failure Quart J Aled' 7 332 33 1938 98 McCHAEL, J Circulatory failure Schuet med fl chnschr 76 851 897 1946 99 MCMICHAEL J Circulatory failure studied by means of venous catheterization Advances in internal Medicine 261 101 1917 100 McVICHEL, ) Heart failure of pulmonary origin Edmburgh VI 5565 11 1918 101 McVICHAEL J Pharmacology of the failing huruan heart Brui Med 1 99 939 1918 107 MCVICIUAEL ) Cardiac venous congestion Its causes and consequences Am J Med 6651 668 1919 105 VCVICHAEL } and SHARPEY SCHAFER FP The action of intravenous digoxin in min Quart ] Ved }} 123 295 1944 ·BIBLIOGRAPHY 65 104 McMICHAEL, J and SHARPLY SCHAFER, E. P Cardiac output in man by a direct Fick method. Ent Heart) 633-40 1944 105 MENEELY GR and KALTREJDER N L. A study of the volume of the blood in con este heart failure Relation to other measure ments in fifteen patients. J Clin Investigation 22 5 1 530 1913 106 MERRILL, A. J. Edema and decreased renal blood fow in patients with chronic congestive heart failure Evidence of forward fail ure" as the primary cause of edema. J Clin Inzestigation 23 389 400 1946 107 VERRILL, A J Mechanisms of salt and water retention in heart failure Am J Med 6 397 367 1919 108 MERRILL, A. J and CARCILI, W H Vechanism of edema formation in thyrotoxic heart disease Am J Med 3 502 503 1917 109 MERRILL, A. J and CARCEL W H The effect of exerase on the renal plasma flow and 6tration rate of normal and cardic subjects J Clin Investigation 27 272 277 1948 110 MERRILL, AJ MORRISOY J L. and BRANSOY ES Concentration of renin in renal venous blood in patients with chronic heart failure. Am J Med 1 468-472 1916 111 NorotoFT R Ross G and LEITER L Renal plasma fow and sodium reabsorpuon and excretion in congestive heart failure J Clin Investigation 27 19 1918 112 MOKOTOFF R, and Ross G The effect of spinal anesthesia on the renal ischemia in congestive heart failure. J Clin Investigation 27 333 339 1918 113 MYERS J D and HICKAM J B An estimation of the bepauc blood fow and splanchnic oxygen consumption in heart failure J Clin Investigation 27 620 627 1918 114 NIELSEN H E. Clinical investivations into the cardiac output on patients with compensated heart disease during test and during muscular work Acta med Scandinav 91 223 266 1937 115 NYLIN G On the amount of and changes in the residual blood of the heart. Am Heart J 25 598 608 1913 116 Nyur G Blood volume determinations with radioactive phosphorus Brit Heart] 7-81 84 1945 117 NYLIN G and HEDLUND S Weight of the red blood corpuscles in heart failure determined with Labelled erythrocytes during and after decompensat on Am Hea ! ] 33770 795 1917 118 OCDEN E The extra renal sequel to experimental renal hypertension Bull N Y Acad Med 23 613 660 1918 119 OCDEN E The organization of cardiovascular function Bull N Y Acad Med 24 561 585 1948 120 Pack I H The Occurrence of a vasoconstrictor substance in blood during shock induced by trauma hemorrhage and burnu Am J Physiol 139 386 398 1943 ·66 HEMODYNAMICS IN FAILURE OF CIRCULATION 121 PAINE R. and SMITH JR The mechanism of heart failure 4 Tésumé of physiologic factors in cardiovascular failure Am J Nied 6 81 102 1919 122 PAYPE S A and PETERS J P The plasma protein in relation to blood hydration VIII Serum proteins in heart disease Clint Investiga tion 11 103 112 1932 198 PETERS J P Role of sodium in the production of edema New England ) Med 239 333 562 1918 124 Philips RA DOLE, P HAMILTON PB EMERSON KJR IRILIBALD R. and VAN SLYKE D D Effects of acute hemor rhagic and traumatic shock on renal function of dogs am) Physiol 145 314 336 1916 125 PLESCH J Physiology and pathology of amount of blood Ztschr klin Med 93 241 281 1922 126 PORTER, R R and Downs R S Some physiological observations on the circulation during recovery from vitamin B deficiency Ann Int Med 17-615 658 1912 127 Pucu LGC and WYNDHAM CL The circulatory effects of mercurial diuretics in congestise heart failure Clin Sc 8 11 19 1919 128 QUATTLEBAUM J J Arteriovenous aneurysm Am Fleart J 13-99 103 1937 199 KRASER PB and Burc GE Raduosodrum tracer studies in con gestive heart failure Proc Sor Exper Biol Ở Med 63 543 546 1946 130 RUCIVAN F and GRANT ! Some observations on the pathogenesis of edema in cardiac failure Am Heart) 32 438-442 1946 131 REID MRand McQUIRE J Arteriovenous aneurysms Ann Surg 108 613-693 1938 132 RICHARDS D W JR The circulation in traumatic shock in man Bull NY Acad Ared 20 363 93 1944 133 RICHARDS DW Jh. Cardiac output by the catheterization technique in various clinical conditions Federation Proc 4 215 2° 1945 131 RICHARDS D W Jr. Observations on the dynamics of the systemic circulation in man. Bull NY Acad Med 22 630 647 1946 135 RICHIARDS D W Jr. Contnbutions of right heart catheterization to the physiology of congestive heart fallure Am J Med 3 431-446 917 136 RICHARDS DW. JR Droamics of congestive heart failure Am J Med 6772 780 1919 137 RICHARDS DW JR. COURNAND A DARLING RCGILLESPIE W H and BALDWIN E DEF Pressure of blood in the right aunde in animals and man Under normal conditions and in richt beart 2lure Am J Physiol 136 115 123 1912 138 RILLY RL HIMMELSTEI A VIOTLEY HL EINE* H M and ·BIBLIOGRAPHY 67 COURNAND A Studies of the pulmonary circulaton at rest and durinexercise in normal individuals and in patients with chronic pulmonary disease. Am J Physio! 15. 3/2 382 1948 159 RODBARD S and WAGNER D By passing the right ventricle Proc Soc Exper Bol & Aled 71 690 1919 140 Roos A and SMITII J R. Production of experimental heart failure 1a dogs with intact arculation Am J Physiol 153 558 566 1918 141 ROUNTREE L G FIT2 R and GERACHTY J T The effects of ex perimental chronic passive congestion on renal function Arch Int Med 11 191 147 1913 142 RYDER H W MOLLE WE and FERRIS E B JR. Influence of the collapsibility of veins on venous pressure including a new pro cedure for measuring tissue pressure J Clin Investigation 3 333 341 1914 145 RYTAND D A Effect of digitalis on enous pressure of normal indi viduals J Clin Investigation 12 847 860 1933 144 SALVESEN HA and LINDER GC Observations on the inorganic base and phosphates in relation to the protein of blood and other body fluids in Brights disease and in heart failure J Biol Chem 58 617 634 1923 145 SCHEMM F R A high fluid intake in the management of edema especially cardiac edema I The details and basis of the regime Ann Int Med 17 952 969 1949 146 SCHEMM F R A high fluid intake in the management of edema especially cardiac edema II Clinical observations and data Ann Int Med 21 937 976 1944 147 SCHROEDER HA Studies on congestive heart failure I The importance of restriction of salt as compared to water Am Heart J "2 141 153 1941 148 SCHÜRMEYER A Ueber Blutmangenbestimmungen bei Herzfehlern Verhandi d deutsch Gesellsch finn Med 40 388 391 1928 149 SELKURT E E Renal blood flow and renal clearance during hemor rhagic shock Am J Physto! 145 699 709 1946 150 SEYMOUR WB PRICHARD WH LONGLEY LP and HAYMAN JV JR Cardiac output blood and interstitial Aud volumes total circulating serum protein and kidney function during cardiac failure and after improvement. ] Cin investigation 2199 240 1942 151 SHARPEY SCHAFER EP Cardiac output in severe anemia Clin Sc 5 125 139 1941 159 SHARPEY SCHAFER EP Transfusion and the anaemic heart Lancet 2-296 .99 1915 153 SHORR E ZWEIFACH B and FURCHGOTT RF On the occur rence sites and modes of origio and destruction of principles affect ·68 HEMODYNAMICS IN FAILURE OF CIRCUI ATION ing the compensatory vascular mechanisms 10 experimental shock Science 102 489-498 1915 154 SINCLAIR SAITI B KATTLS A A GENEST ) and NEWMAN E V The renal mechanisms of electrolyte excretion and the metaboli balance of electrolytes and nitrogen in congestive cardiac failure the effects of exerase rest and aminophyllın Bull Johns Hopkın Hospital 84 369 394 1919 155 SATIRK F H Observations on the causes of edema in congestive hear farlare Clin Sc 317 335 1935 156 SUITIT HW I OVENSINF E A GOLDRING W Custs Hand RANGES HA The effects of spinal anesthesia on the circulation in normal unoperated man with reference to the autonomy of the artenoles and especially those of the renal arculation / Chin Intestigation 18 319 511 1939 157 SMITH WC WALKER GL and ALT HL rhe cardiac output in heart disease I Complete heart block auricular fibrillation before and after restoration to normal rhythm subacute rheumatic fever and chronic rheumatic valvular disease Arch Int Med 45 706 726 1930 158 STARLIN EH Some points in the pathology of heart disease Lancet 1 652 655 1897 159 STARR 1 Role of the statıc blood pressure in abnormal increments of venous pressure especially in heart failure Il Clinical and experimental studies Am y died. Sc 199 440 55 1910 160 STARR I Our changing viewpoint about congestive fallure Ann Ini Med 30 1 23 1919 161 STARR I DOVAL J S JR VARGOLIES A SILAW R COLLINS L II JR and CAMBLE CJ Studies of the heart and crculauon in disease estimations of basal cardiac output metabolism heart size and blood pressure in 235 subjects J Clin Investigation 13 561 599 1931 262 STARRI JEFFERS Y and MEADER}x The absence of con spicuous increments of venous pressure after severe damage to the right senince of the dog with a discussion of the relation between clinical congestive failure and heart disease Am Heart 26291 301 1913 165 STARR I CANBLE C I MARCOLIES A DOVAL, J S je. Joseph N and EAGLE L A clinical study of the action of 10 commonly used drugs on cardiac output work and sizcon respiration on poeta bolic rate and on the electrocardiogram J Clin intestigation 16 799 82$ 1937 164 STARR I and RANSOY A J Role of the static blood pressure" In abnormal jaatements of venous pressure especially in heart fsilure 1 Tbcoretical studies on an improved circulation schema whose ·BIBLIOGRAPHY 69 pumps obey Starling's law of the heart Am J Med Sc 199 27 99 1940 163 STEAD E AR JR Edema of beart failure Bull AY Acad Aled 24 607 614 1918 166 STEAD E. A JR. The role of the cardiac output in the mechanisms of congestive heart failure Am J Med 6232 236 1919 167 STEAD E A JR. and WARREN J V The protein content of extra cellular Quid in normal subjects after venous congestion and in patients with cardiac failure anoremia and fever J Clin Intest 23.183 287 1914 168 STEAD EA JR. and WARREN J Cardiac output in man An analysis of the mechanisms varying the cardiac output based on recent clinical studies Arch Int Med 80 237 248 1947 169 STEAD E A JR. WARREN J V and BRANAON ES Cardiac output in congestive heart failure An analysis of the reasons for lack of correlation between the symptoms of heart failure and the resting cardiac output Am Flearl ] 35 529 541 1948 1,0 STEAD E A JR. WARREN J V and BRANNON ES Effect of lanatoside C on the circulation of patients with congestive failure A study using catheterization of the right side of the heart Arch Int Med 81 282 291 1918 171 STEAD E A JR. WARREN J V VERRILL A J and BRANNON E S The cardiac output in male subjects as measured by the technique of ngat atrial catheterization. Normal values with observations on the effect of anxiety and tilting Clin Inzestigation 24 396 331 1945 172 STEINMANN B Ueber die Bestimmung der zirkulierenden Blutmen, e beim Menschen Arch exper Path u Pharmakol 191.37 262 1938 173 STEWART H J and COHN A E Studies on the effect of the action of digitalis on the output of blood from the heart III Part 1 The effects on the output in normal human hearts Part 2 The cffect on the output of hearts in heart failure with congestion in human beings J Clin Invest gatio 1 11 917 935 1932 174 STEWART HJ CRANE N F WATSON RF WHEELER C and DETTRICK J E The cardiac output in congestive heart failure and in organic disease Ann Int Med 13 23 3 9310 1910 175 SUAREZ J R E FASCIOLO J Cand TAQUINI AC Cardiac output in heart failure Am Heart ] 32 339 356 1916 1,6 SWANK R L PORTER R R and YEOMANS A The production and study of cardiac failure in thiamin deficient dogs Am Heart 22 151 168 1941 177 TALBOTT J H PECORA L J MELYILLE RS and CONSOLAZIO W Renal function in patients with Addison s disease and in patients ·70 HEMODYNAMICS IN FAILURE OF CIRCULATION with adrenal insufficiency secondary to pituitary pan hypofunction J Clin Investigation 21 107 119 1942 178 THOMSON W A R The plasma proteins and cardiac edema Quart Med 3 587 601 1934 179 THORN G Wand EXIFRSOY K JR The role of gonadal and adrenal cortex hormones in the production of edema Ann Int Med 14757 769 1910 180 THORV GW GARRUTT HR HITCHOCK FA and IIARTMAN F The effect of cortin upon the renal excretion of sodium potassium chloride inorganic phosphorus and total nitrogen in normal sub jects and in patients with Addison s disease Endocrinology 21-13 219 1947 181 THREEFOOT S GIBEONS T and BURCH G Relationship of weight venous pressure and radiosodium excretion in chronic congestive heart failure Proc Soc Exper Bol & Med 66 369 372 1947 182 TRUETA Y BARCLAY A E FRANKLIN K J DANIEL P M and PRICHARD V ML Studies of the Renal Circulation 187 PP Springfield Charles C Thomas 1917 183 TURNER H JAMES D F and MERRILL AJ Studies on the mechanism of the reduction in renal blood flow in heart failure Am J Med 5.619 1948 184 WARREN J V BRANNON ES STEAD EA JR and MERRILL AT Pericardial tamponade from stab wound of the heart and pericardial effusion or empyema A study using the method of right heart catheterization Am Heart] 21 418 425 1946 185 WARREN J V BRANAON ES STEAD E A JA and MERRILL, AJ The effect of venesection and the pooling of blood in the ex tremities on the atrial pressure and cardiac output in normal subjects with obser ations on acute circulatory collapse in three instances J Clin Investigation 24 337 314 1945 186 WARREN J V BRANNO ES \\EENS H S and STEAD E A JR. Effect of increasing the blood volume and right atrial pressure on the arculation of normal subjects by intravenous infusions am I Med 4 193 900 1918 187 WARREN MERRILL A J and STEAD EA JR. Role of the extracellular fluid in the maintenance of blood volume J Clin Intestigation 22 635 611 1913 188 WARREN J V and STEAD E A JR. Fluid dynamics in chronic con gestive heart failure An interpretation of the mechanisms producing the edema increased plasma volume and elevated venous pressure in certain patients with prolonged congestive failure Arch Int Med 73 138 147 1911 189 I\ATKINS E JR. PITCAIRN D M and YOUBIANS W 3 Circulatory effects produced by by passiog the right ventricle Unpublished a periments ·BIBLIOGRAPHY 71 190 KERS Ocadental berberi with cardiovascular manifestations. J 1 NA 113-832, 839 1910 191 WEISS S and ELLU L B Circulatory measurements in patients with rheumauc heart disease before and after the administration of digitalis / Clm Investigation 8 439-465 1930 199 WEISS S and HILKINS R. 1 The nature of cardiovascular dis turbances in nutritional deficiency states Ann Int Med 11 104 148 1937 193 MESOV L G, JR Axstow } P. Jr. and SMITH H1 The excretion of strong electrolytes Bull N Y Acad Med 24 586 606 1918 191 WHEELER E O BRIDGES W C and WRITE P D Diet low is salt (sodium) 1B congestive heart failure JAMA 133 16 20 1917 19. WHITE H L HEVEECKER P and ROL D Some endocrine in fluences on renal function and cardiac output. Am J Physiol 149 401-417 1917 196 WICCERS C J The present status of the shock problem physiol Rev .'74 123 1942 197 WINSOR T and BURCH G E. Use of the phlebomanometer Vormal venous pressure values and a study of certain clinical aspects of venous hypertension in man am Heart ] 31 387-406 1946 198 Wood W B and JANEWAY GA Change in plasma volume during recovery from congestive heart failure Arch Int Afed 62 151 159 1938 199 WOOD P and PAULETT J The effect of digitalis on the venous pressure Bnt Heart J 11 83 91 1949 00 YEOVANS A PORTER RR and SWANK RL Observations on certain manifestations of circulatory congestion produced in dogs by rapid infusion Clans Invest gattor 2 33-45 1943

·No text on this page.

·This Book
HEMODYNAMICS IN
FAILURE OF THE
CIRCULATION
Ву
WB YOUMANS MD PHD
and
AR HUCKINS MS MD
was set printed and bound by The Collegiate Press of
Menasha, Wisconsin The type face is Linotype Baskerville
set 11 point on 13 point the type page is 23 by 39 picas
The text paper is 70 lb White Stonewall Eggshell The
cover is No 25 Black Pajco Lexide embossing No 32 77
BOKS
THOMAS
SIMBOL
Vith THOMAS BOOKS careful attention is given to all
details of manufacturing and design It is the Publisher's
desire to present books that are satisfactory as to their
physical qualities and artistic possibilities and appropriate
for their particular use THOMAS BOOKS will be true
to those laws of quality that assure a good
name and nood 7-11

·No text on this page.

·No text on this page.