534 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



the output of the heart is a reflection of venous inflow. 

 In their experiments with the Newell Martin heart- 

 lung preparation, increasing the inflow in canine 

 hearts caused about a fourfold increase in cardiac 

 output and stroke volume as the right atrial pressure 

 was raised from i o cm to 60 cm of blood. Otto Frank's 

 contributions to an understanding of the factors 

 influencing the function of the isolated heart are 

 generally recognized, but Chapman and Wasserman's 

 recent translation of his work (11) should broaden the 

 appreciation of his superlative experimental tech- 

 niques. Experiments by Starling (29), Straub (49), 

 and Wiggers (54) extended and refined these observa- 

 tions. It is not generally realized that Starling's 

 main contribution to the development of heart-lung 

 preparations was an improved means of controlling 

 resistance (22). The generalization which is commonly 

 known as Starling's law of the heart is actually a 

 restatement of conclusions previously enunciated by 

 Blix and Fick for skeletal muscle and by Frank for the 

 myocardium (see ref. 41 ). The experiments conducted 

 by Starling and his colleagues were extremely well 

 designed, meticulously executed, and beautifully 

 described. However, the subsequent extrapolation of 

 the results to normal humans and animals (48) was 

 premature, since the exact nature of the cardiac 

 response during spontaneous adjustments had not 

 been accurately described. 



The principal procediue for increasing cardiac 

 output in experiments on heart-lung preparations 

 was to elevate the ventricular filling pressure by one 

 means or another. The nature of the experimental 

 model led directly to the widely accepted concept 

 that cardiac control is determined principally by the 

 "venous return." "It is axiomatic that the heart can 

 pump only as much blood as it receives. Indeed the 

 volume of blood returned to the heart is the basic 

 determinant of cardiac output" (56). Implicit in the 

 assumption that cardiac output is determined by 

 venous return is the concept that the stroke volume 

 is increased through the Starling mechanism. If 

 these investigators had elected to stimulate the s\m- 

 pathetic cardiac nerves instead of to raise or lower a 

 venous reservoir in order to induce changes in cardiac 

 performance, quite difTerent concepts of cardiac con- 

 trol would have evolved. It might even have been con- 

 sidered "axiomatic" that "the quantity of blood 

 pumped by the heart determines the amount return- 

 ing to the heart, thus the cardiac output is the basic 

 determinant of venous return." 



Although it was generally recognized that changes 

 in the "physiological state" of the myocardium could 



be important determinants of \cntricular per- 

 formance, the Frank-Starling mechanism dominated 

 the thinking about the heart so completely that 

 neural and hormonal regulation of cardiac perform- 

 ance was largely ignored for many years. This situa- 

 tion did not occur in the case of skeletal muscle, whose 

 contractility likewise depends upon its resting length. 

 In this case, the much greater dependence upon the 

 number and pattern of nerve impulses was conspicu- 

 ous even in the isolated preparation. The need for 

 central coordinating mechanisms was more obvious 

 than in the case of a myocardium which could per- 

 form well even without nerves. 



NATURE OF INCRE.'KSED CONTRACTILITY 



Neural and hormonal controls afifect the myocar- 

 dium by inducing changes in its "physiological state"' 

 of the sort elicited by the direct action of epinephrine. 

 The term "increased contractility" has been applied 

 to these changes in myocardial performance. The 

 word "contractility" has a fairly specific definition: 

 namely, the property or capacity of cells for shortening 

 in response to an appropriate stimulus (7). In con- 

 trast, "increased contractility" has been used to 

 indicate many factors in difTerent contexts; it is 

 rarely defined and is replete with sources of semantic 

 confusion. For example, "increased contractility'' 

 has been applied to increased stroke volume (15), 

 increased force of contraction (6), and increased 

 "vigor" and "velocity" of contraction (43, 55). The 

 ventricular function curves devised by Sarnoff and 

 his colleagues (40) describe or define changes in 

 contractility in terms of energy released by the heart. 

 Changes in contractility have also been defined in 

 terms of peak contractile tension or peak systolic 

 pressure, rate of pressure rise or fall, duration of 

 contraction, degree of contraction, and other facets 

 of contraction in various combinations. 



If neural and hormonal mechanisms are important 

 in cardiac control and if they exert their influence 

 by producing clianges in contractility, this term must 

 be more fully and accurately defined. It is also impor- 

 tant to decide whether contractility is really a single 

 mechanism or is a group of mechanisms arbitrarily 

 designated by a single term. Evaluation of tlie nature 

 of contractility requires analysis of many different 

 factors — more than can be conveniently measured in 

 human subjects. However, recently developed tech- 

 niques (2) make possible continuous analysis of many 

 dillVrent aspects of left ventricular performance in 

 healths- active clogs (fig. i). 



