ROLE OF NOREPINEPHRINE RELEASE IN THE INTERVAL-STRENGTH RELATIONSHIP OF HEART MUSCLE’2

The importance of the interval between con-tractions of heart muscle for the strength of con-traction has been appreciated for almost 100 years (Bowditch, 1871). Today the term “in-terval-strength relationship ” encompasses all direct effects of cardiac rate and rhythm on myocardial contractile performance (Koch-Weser and Blinks, 1963). Of foremost physiologic importance is the influence of the frequency of activation of the heart on the strength and time course of its contraction (Koch-Weser, 1963; Koch-Weser and Blinks, 1963). Other manifes-tations of the interval-strength relationship include the transient changes in myocardial con-tractility which follow sudden changes in fre-quency and those seen with one or more prema-ture beats or after periods of inactivity. All such interval-dependent changes in contractility arise from changes both in the duration of the active state and in the degree of activation of the contractile element (Koch-Weser and Blinks, 1963). Changes in the latter can be accounted for by the complex interactions of two opposing, interval-dependent factors which modify basal contractility: the positive and the negative inotropic effects of activation (Blinks and Koch-Weser, 1961; Koch-Weser and Blinks, 1963). However, the nature of the changes in the myocardium which are responsible for the in-terval-strength relationship remains to be estab-lishecl. In both atrial and ventricular myocardium of almost all mammalian species contractility is raised by increases in frequency of contraction over a wide range (Koch-Weser, 1963; Koch-Weser and Blinks, 1963). Since this range in-cludes most rates observed in vivo, this aspect of the interval-strength relationship has at-tracted most attention. One popular hypothesi