THE CONTROL OF THE FUNCTION OF THE HEART 



499 



250 





 40 



ra^ft 



FIG. 7 



IVD 



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5 

 4 

 3 

 2 h 



I 

 •- 



veloped per minute. A greater relative increase in 

 stroke volume, with mean aortic pressure and heart 

 rate held constant, resulted in a much smaller aug- 

 mentation of the total tension developed. .A.s shown 

 above, increases of rate or aortic pressure produced 

 the exhibition of a marked homeometric influence, 

 whereas with the augmentation of stroke \'olume 

 this was relatively less well developed. It seems not 

 unreasonable to suggest, therefore, that an increase 

 in the amount of tension developed by the myocar- 

 dium per unit of time may be that cardiodynamic 

 factor which elicits homeometric autoregulation. 



2) Ionic concentration changes. Bowditch (12) in 1871 

 described phenomena in the Irog heart which he re- 

 ferred to as "treppe" or staircase. Shortly after the 

 onset of stimulation, the heart exhibited successively 

 stronger contractions with each succeeding stimulus 

 until, several beats later, a plateau was reached; 

 subsequent increases in rate produced the same effect. 

 A common variant of the Bowditch staircase is shown 

 in figure 65; after the change of rate in the isolated 

 rat ventricle strip, an increase in contractility became 

 apparent, i.e., a stronger contraction from the same 

 initial tension. The greater the rate change imposed, 

 the greater was the increase in contractility at the 

 new rate and the stronger were the first few con- 

 tractions after the return to the control rate. The 

 similarity between the patterns observed in figure 

 65 with those observed in figures 6A and C support 

 the position put forth by Rosenblueth et al. (83) 

 that the Bowditch staircase effect is operative in 

 the adequately supported canine heart, a position 

 consonant with the experiments of Braunwald et al. 

 (14) in which it was observed that the higher the 



heart rate the shorter was the period of time required 

 for the \entricle to eject a given volume. 



Bowditch put forward the idea that each contrac- 

 tion leaves behind it a more favorable state for the 

 ensuing contraction and thus, the higher the rate, 

 the more favorable is the condition for contracting. 

 The available evidence relating to the biochemical 

 mechanism by which this takes place can be found 

 in the recent review of Hajdu & Leonard (43), and 

 indicates that potassium leaves the myocardial cell 

 with each contraction and reenters it in the interval 

 between contractions. Thus, the higher the rate and 

 the shorter the period of diastole, the less would be 

 the opportunity for re-entry of potassium relative to 

 efflux and the lower the intracellular potassium in 

 the new equilibrium state, a condition known to 

 increase contractility (43). It has, in fact, recendy 

 been demonstrated (17, 27) that a potassium loss 

 will occur in the perfused canine heart when tachv- 

 cardia is imposed. 



A certain similarity is to be noted between the 

 cardiodynamic pattern elicited when activity is in- 

 creased either by increasing heart rate or by increas- 

 ing aortic pressure (fig. 5, upper). In both, phase 2 

 shows that an increase in contractility is taking place 

 soon after the beginning of the intervention; in both, 

 phase 4 shows that an increased contractilitv has 

 occurred during the intervention. This similaritv of 

 patterns suggests that changes in intracellular ionic 

 concentration may take place as a result of the change 

 in the character of the contractions as well as bv the 

 length of the interval between them. This view pre- 

 supposes that a more forceful contraction can either 

 increa.se ionic efflux during the contraction or, per- 

 haps less likely, .so predispose the membrane as to 

 alter net ionic flux in any given time interval between 

 contractions. In any case it now seems clear that, 

 over a wide range, an increase in the amount of 

 tension developed by ventricular myocardium can 

 produce a biochemical rearrangement which leaves 

 beliind it a more favorable condition for subsequent 

 contractions, and that this phenomenon is not wholly 

 dependent upon an increased coronary flow. 



jj) Norepinephrine. In any given isolated heart 

 preparation, an aortic resistance can be selected 

 against which the ventricle is unable to eject the same 

 or nearly the same stroke volume without requiring 

 an elesated LVED pressure. Figure 8.4 shows such 

 an instance. Between panels 1 and 2 aortic resistance 

 was abrupth' increased. During the administration 

 of norepinephrine (panels 3 and 4), the same aortic 

 resistance increase did not then require an appre- 



