490 



HANDBOOK OF PHVSIOLOGV 



CIRCULATION 



This general statement by Starling & \'erney (i 15) 

 still seems to have merit in establishing the general 

 guidelines for continuing investigation in physiologi- 

 cal research. It will serve as the basic pattern of 

 presentation in this chapter. 



The inadequacies of communication ha\e rarely 

 been more apparent in a scientific discipline than in 

 cardiovascular physiology, or so it seems. To mitigate 

 this, at least somewhat, it appears wise to designate at 

 the outset the specific meaning of certain terms. The 

 term "autoregulation" will be used to describe 

 phenomena occurring in an organ which are not 

 attributable to nervous or chemical influences origi- 

 nating outside that organ and which phenomena can 

 reasonably be construed as being of value to the per- 

 formance of the total organism. The term "myo- 

 cardial contractility" will be used in a specific 

 manner. When, from any given end diastolic pressure 

 or fiber length, the ventricle produces more external 

 stroke work and more external stroke power (stroke 

 work per systolic second) an increase in ventricular 

 contractility is said to have taken place and vice 

 versa. Implicit in this definition is an increased rate 

 of development of tension when contractility in- 

 creases. Specifically excluded is any increased work 

 that may be done as the result of afterload from the 

 same end diastolic length, since the rate of develop- 

 ment of tension is not increased under such circum- 

 stances prior to the application of the afterload (36, 

 37). The term "ventricular function curve" (VFC) 

 will be used to designate a) the relation between 

 mean left atrial pressure and left ventricular stroke 

 work (VFCla), b) the relation between left ventricu- 

 lar end diastolic pressure and left ventricular stroke 

 work (VFClv), and c) the relation between changes 

 in left ventricular myocardial fiber length and changes 

 in left ventricular stroke work (VFCfl)- When the 

 terms stroke work and stroke power are employed 

 they will always refer to external stroke work and 

 external stroke power. The term "filling pressure" 

 will be used to indicate mean atrial pre.ssure. The 

 term "pressure-length relation" will be used to in- 

 dicate a curve describing the relation between changes 

 in the length of a selected segment of left ventricular 

 myocardium and simultaneous changes in left 

 ventricular diastolic pressure (58). The methodolog>' 

 and methods of calculation used in the indi\idual 

 experiments discus.sed will be alluded to only where 

 it seems especially desirable, since such information 

 can be obtained in the .source material referred to. 



Cardiac as well as skeletal muscle will, within 

 certain limits, contract more forcefully from a longer 



initial length. As will be observed from the outline 

 above, this fundamental fact will serve as the point 

 of departure in the analysis of the system complex 

 under consideration. 



I. PERFORMANCE CHARACTERISTICS IN THE ISOLATED 

 HEART (intrinsic MECHANISMS) 



A. The J'enlru/e 



heterometric AUTOREGULATION. One type of in- 

 trinsic response exhibited by the ventricle of the 

 isolated heart is the well-known Frank-Starling 

 mechanism. This endows the ventricles with per- 

 formance characteristics such that the heart ejects 

 whatever volume is put into it. For, if inflow is aug- 

 mented and end diastolic pressure and fiber length are 

 thus increased, the ventricle contracts more forcefully 

 and expels an augmented stroke volume. This occurs 

 on a beat-to-beat basis. Because this basic mechanism 

 employs a change in initial fiber length, it is desig- 

 nated as heterometric autoregulation. 



In 1878 Waller (121) suggested that when "the 

 left ventricle is forced to work against a higher pres- 

 sure, it has to be filled abundantly and under high 

 pressure." Fick (38), in 1882 and Blix (11), in 1895 

 disclosed the fundamental relationship between the 

 initial length of skeletal muscle and the force of its 

 subsequent contraction. In the same year Frank (39) 

 published his exciting observations on the dynamics 

 of cardiac muscle, a treatise now more readily avail- 

 able to English speaking investigators as a result of 

 the translation of his work by Chapman and Wasser- 

 man (40). Starling and his co-workers (113) sub- 

 sequently began the first major attempt to systematize 

 the pertinent operating parameters relating to the 

 mammalian heart into a cogent and useful generality, 

 and the result of their efforts came to be known as 

 Starling's law of the heart. The advent of this work 

 was greeted with enthusiasm not only by physiolo- 

 gists but also by those interested in the clinical 

 aspects of circulatory problems, since it promised to 

 be a valuable conceptual tool in making many 

 observed phenomena more readily comprehensible. 

 This initial enthusiasm was, however, gradually 

 replaced by a growing disillusionment with the 

 over-all helpfulness of the concept for two main 

 reasons. The first is that many who attempted to use 

 this concept did .so with an inadequate appreciation 

 of the essential operating parameters. More im- 

 portant, however, were those investigations demon- 



