Potentiation of Myocardial Contractility by Continual Premature Extra-activations

Introduction of a premature activation into each interval between regular contractions of isolated kitten papillary muscles greatly increases isometric tension development. This premature extra-activation potentiation is a manifestation of the interval-strength relationship of ventricular myocardium and results both from the increase in the overall frequency of activation (frequency potentiation) and from the prematurity of the extra-activations (prematurity potentiation). A premature electrical stimulus which elicits a propagated action potential is always followed by a mechanically apparent activation of the contractile element. Potentiation of the regular contractions follows from the occurrence of premature, propagated action potentials, and/or the resulting activation processes. It does not depend on the extent to which the contractile element can respond to the premature activation. Prematurity potentiation results solely from an increase in the degree of activation of the contractile element. It increases over a wide range with the prematurity of the extra-activation but always decreases when the prematurity interval approaches the refractory period closely. The extent of prematurity potentiation varies with the basal frequency of contraction; it tends to raise tension development to the same high level whatever the basal frequency. Although nonpotentiated strength of contraction increases greatly with frequency, potentiated contractions at low frequencies are stronger than nonpotentiated contractions at high frequencies. At normal temperature summation of contractions plays no role in prematurity potentiation. Similarly, release of endogenous norepinephrine is not involved, but such release does occur and interferes with the study of potentiation when high-intensity stimuli are used. Premature activations may transiently alter the concentration of available Ca ++ in an intracellular site critical for activation of the contractile element.