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Pharmacological Reviews, Vol 15, 531-599, Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics
1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
In most areas of pharmacology knowledge about the mechanism of action of drugs has advanced in pace with the understanding of the systems in which the drugs act. Despite great progress toward an understanding of the nature of muscular contraction, however, practically nothing is known about the mechanisms of action of drugs that affect myocardial contractility. The heart is a muscle, and much can be gained by applying the concepts of muscle physiology to the study of its function. The effects of drugs can then be defined in terms more precise than simply the direction and magnitude of the change produced in the strength of contraction. Similar changes in the strength of contraction can result from quite different changes in the fundamental mechanical properties of the muscle. An understanding of the effects of drugs in terms of their actions upon these properties seems essential for further progress.
The influence of physical factors on the contractions of the heart must be given careful consideration in the design and interpretation of experiments on the inotropic actions of drugs. Such actions vary quantitatively or even qualitatively with the physical conditions of the experiment: the frequency of contraction is particularly important in this regard [see companion review (258a)]. In some cases, the actions of physical and chemical determinants of contractility are so closely related that they cannot profitably be studied separately. Interactions of this sort challenge explanation; they may furnish a valuable approach to the study of the mechanisms of action of both factors concerned.
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