548 



HANDBOOK OF PHVSIOLOGV 



CIRCULATION I 



permits vascular adaptation to a change in the local 

 environment. In spite of much work on this subject, 

 the exact nature of these peripheral vascular controls 

 remains mysterious. 



Similarly, the isolated heart displays a remarkable 

 ability to adjust its performance in response to induced 

 changes in the conditions under which it functions, 

 for example, filling pressure and outflow pressure. The 

 fact that the heart can alter its work output under 

 experimental conditions without normal neural con- 

 trols does not necessarily mean that these responses 

 are essential or dominant during normal function. 

 In the past, most physiological investigations of 

 cardiac control have been conducted on anesthetized, 

 thoracotomized dogs, a preparation in which the heart 

 is divorced from influence by the higher levels of the 

 nervous system nearly as effectively as it would be 

 if the brain stem were transected above the medulla. 

 Under these conditions, the heart responds in accord- 

 ance with the Frank-Starling mechanism unless the 

 "physiological state" of the myocardium is altered. 

 Starling was fully aware of the profound changes in the 

 functional properties of the myocardium induced by 

 the administration of catecholamines or by autonomic 

 activity. The ventricular function curves of SarnofT 

 and his associates represent a graphic description of 

 this principle that the Frank-Starling relationship 

 can be altered profoundly by changes in contractility. 

 However, it now seems clear that changes in the 

 myocardial contractility are far more prominent in 

 cardiac control than the Frank-Starling mechanism, 

 unless the neural control mechanisms are suppressed 

 or eliminated. Removal of the neural control discloses 

 the peripheral mechanisms which take over the 

 cardiovascular adjustments and serve as .secondary 

 bulwarks of regulation. They do not provide such 

 rapid or effective adjustments as the normal neural 

 mechanisms, but they do very well indeed (see ref. 



3. 4'). 



A great deal of semantic confusion has resulted from 

 a failure to distinguish between the integrated neural 

 responses and the peripheral mechanisms of control. 

 Although both of these regulating systems are of 

 importance and interest to physiologist and clinician 

 alike, the neural control mechanisms normally 

 dominate the picture under almost all normal con- 

 ditions except changes in posture, as judged from 

 currently available evidence. 



SUMMARY 



Cardiac output is adjusted in response to variations 

 in requirements primarily by changes in heart rate 



and stroke volume. The heart rate is controlled by 

 the reciprocal eff'ects of the sympathetic and para- 

 sympathetic nerves distributed to the pacemaker 

 region. Mechanisms for adjusting stroke volume have 

 received the most attention, and are described in 

 terms of the length-tension relationship of myo- 

 cardium (Frank-Starling mechanism) and change^ 

 in the "functional state" of the myocardium ("con- 

 tractility"). The term "increased contractility" has 

 been used to denote many different characteristics of 

 myocardial or ventricular contraction, including the 

 rate of ejection or ejection velocity, the degree of 

 ejection, the rate of ventricular pressure rise and fall, 

 the ventricular tension developed, and "vigor" and 

 velocity of contraction. 



By means of direct recordings of effective left 

 ventricular pressure, left ventricular diameter and 

 outflow, supplemented by functions derived from 

 these by electronic analogue computers, a graphic 

 definition of contractility was obtained in the form 

 of a continuous analysis of ventricular performance as 

 affected by /-epinephrine. The same kind of analysis 

 demonstrated that the length-tension relationship 

 (Frank-Starling mechanism) was readily demon- 

 strable during changes in posture and exaggerated by 

 centrifugal forces. Variation in "contractility," 

 induced primarily by sympathetic nerx'ous activity, 

 was clearly the dominant mechanism in the cardiac 

 adjustments occurring during other forms of spon- 

 taneous activity by healthy alert dogs. Available 

 evidence indicates that there is a considerable paral- 

 lelism between the responses in dogs and man. 



Changes in "contractility" were found to involve 

 changes in the rates of \entricular contraction and 

 relaxation without much change in the stroke volume 

 or stroke work during the kinds of activity encountered 

 in everyday living. The usual procedure for comput- 

 ing stroke work, from mean values for systolic pressure 

 and for stroke \olume, could easily give the .same 

 numerical \alues for the two sets of patterns (control 

 and after /-epinephrine) in figures i and 2. In fact, 

 computations of stroke work neglecting the kinetic 

 energy involved in the increased ejection velocity 

 underestimate true values by as much as 35 per cent. 



In its most common application, the term "in- 

 creased contractility" encompasses many different 

 physiological mechanisms: the rate of excitation of 

 the myocardial bundles, the rate of contraction of 

 the contractile elements, the rate of recovery of the 

 myocardial cell membrane potentials, the degree of 

 shortening; of contractile elements, and probably 

 others which are not currently suspected. Complete 

 description and elucidation of the various facets of 



