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

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The interval between beats greatly influences the strength of myocardial contraction. Manifestations of this interval-strength relationship include the dependence of contractility on frequency of activation and the effects on contractile performance of sudden changes in frequency, of premature activations, and of periods of inactivity. In isolated myocardium of kittens all these manifestations are unchanged when the cardiac norepinephrine stores are depleted by pretreatment with reserpine or when the beta adrenergic receptors are blocked by pronethalol or propranolol. These findings indicate that norepinephrine release from sympathetic nerve endings in the myocardium plays no role in the genesis of the fundamental interval-strength relationship of heart muscle.

Electrical excitation of heart muscle with stimuli of barely suprathreshold intensity at rates up to 200 per minute produces no inotropically apparent norepinephrine release. The higher the frequency of stimulation the closer to threshold must be the voltage to avoid such release. At any frequency, stimulation intensity is too high if a decrease in voltage lowers contractility. Markedly suprathreshold stimuli cause a frequency-dependent release of norepinephrine at all rates above 5 per minute. This release greatly alters all manifestations of the interval-strength relationship, and such stimuli cannot be used in studies on the mechanism of this relationship.

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