8 



HANDBOOK OF PHVSIOLOGV 



CIRCULATION I 



co-workers (36, 37) have related ventricular pressure/ 

 volume curves to work diagrams, and focused atten- 

 tion on factors afTecting stroke work. Sarnoff and 

 collaborators (53) have related stroke work of the 

 right and left ventricles to pressures in corresponding 

 atria as ventricular function curves. More recently, 

 they restressed the importance of ventricular tension- 

 time in cardiodynamics, and revived the old idea 

 that the force of atrial contractions is of controlling 

 importance. Nylin, Bing, Holt, and their respective 

 collaborators have measured the residual ventricular 

 volumes more accurately, and others have emphasized 

 the emergency value of the "cardiopulmonary re- 

 serve" in increasing cardiac output. Holt and Duo- 

 marco, independently, have shown the importance 

 of end-systolic pressure as an additional regulatory 

 coefficient of cardiac output and work. Guyton and 

 his group (26) have studied the intrinsic response of 

 the ventricles to changes in venous return in dogs 

 whose reflexes were all abolished. Rushmer and his 

 school (5 1 ) developed many ingenious appliances 

 that permitted continuous qviantitative recordings of 

 multiple cardiac activities in unanesthetized dogs. 

 They concluded that changes in cardiac output during 

 exercise are caused entirely by chronotropic and ino- 

 tropic effects mediated by the diencephalon and 

 modulated by reflexes of vascular origin. Thus the 

 wheel of circulation research has revolved back to 

 concepts prevalent at the beginning of the present 

 centurv. 



Methods for Determining Cardiac Output in Man 



Pari passu with the growth of laboratory techniques 

 for elucidating mechanisms of cardiac adaptation, 

 continued efforts were made during the present 

 century to establish more reliable methods for meas- 

 uring cardiac output in man. While many technol- 

 ogies, such as roentgenkymography, cineroentgeno- 

 graphy, electrokymography, ballistocardiography and 

 the integration of pressure pulses achieved some 

 measure of usefulness, the greatest advances have 

 come from improvements in the application of the 

 Fick principle and the blood-dilution technique of 

 Stewart-Hamilton [Hamilton (28)]. Early attempts 

 to obtain probable values for blood gases indirectly 

 or to use foreign gases led to many confusing results 

 (9, 25, 28, 63). Two technical developments — Stadie's 

 method of obtaining arterial blood samples by arterial 

 puncture (55) and Cournand & Ranges" method for 

 obtaining mixed venous blood by cardiac catheteriza- 

 tion (12) — were largely responsible for the great 



impetus to recent studies of cardiac output in man 

 under normal and pathological conditions. For in- 

 stance, it was definitely established (14, 28, 43) that 

 cardiac output may increase from about 4 liters per 

 ininute at rest to 20 or more liters per minute during 

 strenuous exercise. Simple calculations indicate that 

 the heart cannot deliver such large quantities of blood 

 by an increase in heart rate, say from 70 to 180 per 

 min, without considerable increase in stroke volume. 

 Nevertheless, the net information gained by other 

 avenues of approach led to the conclusion of a con- 

 ference in 1955 (59) that the Frank-Starling postulate 

 is operative only to a minor degree (52) : For example, 

 the views were well documented that demonstrable 

 changes in end-diastolic tension and ventricular size 

 were not necessarily associated with more forceful 

 ventricular beats and that both systolic and diastolic 

 sizes decreased as the heart accelerated during ex- 

 ercise. It was not generally recognized that these 

 conclusions corresponded in great detail with those 

 of Henderson (29) in his 1923 review. However, it 

 must be noted that at that time Henderson slyly 

 amended his concept of the imiformity of cardiac 

 behavior by adding an intrinsic ability of the ven- 

 tricles to alter their process of filling and ejection. 



There is no doubt that the current emphasis on the 

 central nervous system control of cardiac output (60, 

 61) was strongly influenced by advances in the field 

 of neurophysiology, chiefly in unraveling the structure 

 and functions of the reticular formation and dienceph- 

 alon. This is a good illustration of how advances 

 in one field of physiology accrue through those made 

 in cognate ones. In our zeal to accept such a concept 

 we must not lose sight of the fact that physical and 

 chemical changes in the environment of cardiac 

 tissue also aflfect its reactivity. Indeed, with the rapid 

 development of endocrinology and knowledge that 

 hormones, such as epinephrine, pitrcssin, thyroxin, 

 and aldosterone, cause changes in cardiac reactivity, 

 one senses alreadv an inclination in some laboratories 

 to postulate a dominant endocrinological control of 

 cardiac output. 



Venous Return, the Fulcrum of the Circulation 



Regardless of the direction that future thinking 

 with regard to the mechanisms of cardiac adaptation 

 to stresses may take, it must conform to the obvious 

 fact that the heart cannot pump more blood than is 

 returned. As phrased by Henderson, "'venous return 

 is the fulcrum of the circulation." The present author 

 finds it ditlicult to understand wh\- so much current 



