498 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



Depending on the initial heart rate, the state of the 

 heart and the stroke x'olume, the L\'ED pressure 

 may not return to or below its initial level during the 

 interval when heart rate is increased (fig. 5, upper 

 right). However, the stigmata of an increasing con- 

 tractility (the decline of L\'ED pressure during phase 

 2) and of an increased contractilitv (L\'ED pressure 

 lower than control \alue at beginning of phase 4) 

 were always observed when a period of relative 

 tachycardia was imposed. Further, the changes 

 observed were a function of the extent of the increase 

 in heart rate imposed. This is shown in figure 6C', 

 an experiment in which the heart rate was increased 

 10, 20, 30, 40, 50, and 60 beats per min from a 

 control level of 128 beats per min. It was observed 

 that the greater the heart rate change, the larger were 

 the changes observed during phases 2 and 4. It was 

 also found that, with coronary flow held constant, 

 the greater the change in rate, the greater was the 

 widening of the coronary A-VO2 difference (fig. 6C). 



Figure 65 shows the change in developed tension 

 resulting from changing the stimulus rate in a prepa- 

 ration consisting of a strip of rat right ventricle in 

 oxygenated Krebs' solution. Since resting tension 

 did not change, an increase in contractility is indi- 

 cated by a greater downward deflection. In the trac- 

 ing shown in figure 65 the rate was changed from 30 

 to 60 (left), 30 to go (middle), and 30 to 108 (right) 

 per min; in each instance the rate was then promptly 

 returned to 30 per min. The pattern of changes ob- 

 served in figure 6.1 and figure 6B are similar in that 

 an increased contractility had been induced in both 

 by an increased rate. Figure 6B also relates to figure 

 6C; in both, the greater the increase in rate, the 

 greater was the relative increase in contractility in- 

 duced as evidenced by phases 2 and 4. 



j) Stroke volume. The transient phenomena ob- 

 served when abruptly changing cardiac inflow are 

 shown in C and E of figure 5 (lower). In this experi- 

 ment the inflow was aliruptly increased without 

 changing either aortic resistance, heart rate, or coro- 

 nary flow (see below). 



Possible mechanisms involved in homeometric autoregula- 

 tion. i) Tension time index (TTI). Rosenblueth et al. 

 (82) stressed "the influence of previous activity" on 

 the contractility of the right ventricle. They state: 

 "We suggest that whenever the work of the heart 

 increases, this increment determines a further in- 

 crease in the subsequent contractions and this in- 

 fluence is important enough to overcome that of the 

 initial volume or length," and, "Any increase of work 

 augments the amplitude of the following contrac- 



tions." Subsequently, however, it was shown (104) 

 that the homeometric influence on the contractilit\- 

 of the ventricle was related to the manner in which its 

 activity was increased rather than the increase in 

 work, per se. Examples of this are shown in figure 5 

 (lower). In the first three panels work was increased 

 100, 1 10, and 145 per cent, respectively, the first two 

 increases being accomplished by elevating aortic 

 pressure and the third primarily h\ increasing flow 

 with only a slight ele\ation in pressure. The exhibi- 

 tion of homeometric autoregulation was clearly more 

 pronounced in the first two. In the latter two panels 

 of figure 5 (lower), later in the same experiment, 

 work was increased 1 30 per cent by elevating aortic 

 pressure (fourth panel) and 86 per cent, predomi- 

 nantly, by increasing flow (fifth panel). Again, the 

 homeometric effect was more pronounced when 

 pressure was increased than when flow was increased. 

 Further, it was possible to induce homeometric 

 autoregulation in the heart even when work was de- 

 creased as shown in figure 7, an experiment in which 

 aortic resistance was abruptly increased and cardiac 

 inflow decreased, such that a fall in stroke work from 

 1 8. 9 to 13.8 g-m occiu-red. Coronary flow rose and 

 arteriovenous O2 difference narrowed, resulting in 

 an increased O2 consumption even though stroke 

 work fell as in similar experiments reported pre- 

 viously (100). The phase i transient and the initial 

 beats of the phase 4 transient are of no value in 

 such an experiment, since a variable effect on these 

 can be obtained, depending upon the point in the 

 cardiac cycle when the changes of inflow and aortic 

 resistance are made and the extent to which they are 

 simultaneous. The findings in phase 2 and most of 

 phase 4, however, are informati\'e. The continuing 

 decline in L\'ED pressure during phase 2 indicates 

 an increasing ventricular contractility for an appre- 

 ciable period after the new, lower stroke work level 

 had been achieved. The continuing rise in L\'ED 

 pressure after removing the imposed intervention 

 shows a reversal of the change in contractility that 

 had taken place. 



An analysis of those hemodynamic variables in- 

 fluencing the oxygen consumption of the heart re- 

 vealed that the variable which most closely correlates 

 with myocardial qO-i is not the work of the heart but 

 rather the amount of tension developed h\ the myo- 

 cardium as indicated by the area under the systolic 

 portion of the pressure curve per minute (100). It 

 was observed in those studies that an increase of 

 aortic pressure or heart rate required the heart to 

 produce a large increase in the total tension de- 



