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Pharmacological Reviews, Vol 15, 601-652, Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics
1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
The last few years have seen significant progress toward an understanding of the interval-strength relationship of heart muscle, particularly in regard to the relation of the various constituent phenomena to one another. It has become clear that interval-dependent changes in myocardial contractility result both from changes in the duration of the active state and from changes in the degree of activation of the muscle; the changes in the degree of activation can be analyzed in terms of the interaction of three factors.
Unfortunately, knowledge about the interval-strength relationship is restricted almost entirely to the level of a descriptive analysis. The nature of the underlying processes in the myocardium remains unknown, though some hypotheses about them can now be rejected with certainty, and some promising clues have been uncovered. Interval-dependent changes in the duration of the active state appear to be related to changes in the duration of the action potential; those in the degree of activation fall in the broad category of changes in excitation-contraction coupling. The study of the cardiac action potential and that of excitation-contraction coupling in striated muscle are both fields of widespread interest and activity, and it can be anticipated that as more is learned about these subjects, the nature of the processes underlying the interval-strength relationship will become clearer. Light may be shed on the character of these processes by studies of the influence of various physical and chemical factors on the interval-strength relationship. It is not enough to determine the effect of such agents on the strength of contraction at various frequencies, however, or to examine the effect of an intervention on a special case of the interval-strength relationship, such as post-extrasystolic oil post-stimulation potentiation. Experiments must be designed in such a way that it can be determined which of the interval-dependent determinants of the strength of contraction are involved in any changes observed. Just as studies of the actions of drugs on the interval-strength relationship are likely to prove helpful in the effort to learn its basic nature, they also may lead to a better understanding of the mechanisms through which drugs alter myocardial contractility.
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