THE CONTROL OF THE FUNCTION OF THE HEART 



493 



caused the heart to return toward its initial \okime. 

 He stated that when adrenahne had been given 

 previously, ventricular volume returned to its control 

 value during the period of increased aortic resistance, 

 presumably while the ventricle was ejecting com- 

 parable stroke volumes and doing more stroke work 

 (3-5). Starling, in whose laboratory Anrep's experi- 

 ments were performed, made similar observations and 

 attributed these phenomena to the presumed im- 

 provement in myocardial metabolism which ac- 

 companies the increase in coronary flow when the 

 aortic pressure is elevated (72, 112, 113). Any ap- 

 prehension concerning the possibility that the hazards 

 of biventricular oncometry were operating was 

 dispelled by the observations made in the tortoise 

 heart by Kosawa (56J, Peserico (73), and Stella (i 16). 

 In 1938 Miiller (68) examined the response of the 

 heart to an increased aortic pressure, both in the 

 intact heart and the isolated left ventricle, and con- 

 cluded that two processes were operative. The first 

 was active immediately, demanding an increase in 

 the heart volume and utilizing elastic forces; the 

 second occurred within 1 to 2 min and enabled the 

 heart to work against the same high pressure with a 

 smaller volume, demonstrating a marked positive 

 inotropic effect. In 1956, Stainsby et al. (iii) pre- 

 sented data obtained from the isolated supported 

 canine heart preparation as well as from nonisolated 

 hearts (13); they showed that when the work of the 

 ventricle was increased by inci easing aortic pressure 

 it produced more stroke work from any given filling 

 pressure than when the increase in work was induced 

 by increasing stroke volume. Further, with stroke 

 volume held constant at each of .several different 

 levels, when the aortic resistance and pressure were 

 then elevated, the ventricle could produce sub- 

 stantial increases of external stroke work with little 

 or no increase in filling pressure. Similar findings 

 were observed by Braunwald rt al. (13). These data 

 in the canine heart were consonant with the findings 

 of Kosawa, Peserico, and Stella in the tortoise. 



Numerous problems of fundamental interest and 

 importance devolved from these considerations. In 

 1959 a major finding was contributed by Rosen- 

 blueth and colleagues (82). Those investigators 

 studied the right ventricle of the isolated dog heart 

 while keeping coronary perfusion (aortic) pressure 

 constant, and while observing changes in the com- 

 bined volume of both ventricles by oncometry. They 

 stated that when the resistance to right ventricular 

 ejection was increased, the combined ventricular 

 volume first increased but then declined while the 



right ventricle ejected a comparable stroke volume 

 against the higher pressure. Although it was ap- 

 parently not possible in their experiments to ascertain 

 what changes in coronary flow actually took place 

 during the transition from one state to another, these 

 experiments nevertheless indicated that an increase 

 in coronary perfusion pressure is not a necessary 

 concomitant of the increase in myocardial contrac- 

 tility observed when the resistance to right ventricular 

 ejection is elevated. 



Hemodynamic factors eliciting homeometric autoregula- 

 tion. i) Aortic pressure (Anrep effect). The effect on 

 L\'ED pressure of abruptly increasing the resistance 

 to ventricular ejection can be seen in figure 3, which 

 shows tracings from experiments in which left coro- 

 nary flow was either controlled or independently 

 varied in an isolated supported heart preparation 

 (104). Figure 3.4 shows high speed tracings shortly 

 before and i min after abruptly imposing a sustained 

 increase in aortic resistance. Stroke volume changed 

 only slightly, from 9.6 to 9.0 ml, and total coronary 

 flow remained essentially the same. The left ventricle 

 increased its stroke work from 8.2 to 15.2 g-m without 

 an increase of end diastolic pressure. It required 52 

 msec to raise its pressure from end diastolic to 40 cm 

 HiC) while facing the low resistance, and only 39 msec 

 to produce the same pressure increment when facing 

 the high resistance. The middle set of tracings (fig. 

 35 ) also shows a pattern of increased ventricular 

 contractility when a high resistance to ejection is 

 imposed. Again, in this instance, stroke volume 

 changed little, from 1 1 .3 to 10.6 ml. Stroke work in- 

 creased from 9.5 to 16.4 g-m, whereas coronary flow 

 was essentially unchanged. When ejecting against 

 the higher resistance, and while producing more 

 stroke work, the L\ ED pressure was 2.4 cm lower. 

 There was a more rapid dev^elopment of pressure at 

 the beginning of ventricular systole, and a shorter 

 systolic ejection time as well as a more rapid decline 

 of ventricular pressure after the incisura; a longer 

 diastolic time appeared just as when sympathetic 

 stimulation is applied (see below). 



Figure 3C shows data from experiments in which 

 an attempt was made to induce a change in con- 

 tractility by altering coronary flow while keeping 

 the resistance to ventricular ejection constant. The 

 tracing in the left panel was obtained without pump- 

 ing the coronary flow and with a screw clamp on the 

 left coronary inflow tubing tightened so as to limit 

 the total coronary flow to the level shown. Without 

 altering aortic resistance, the screw clamp on the 

 coronary tubing was then remov-ed; coronary flow 



