MECHANISM OF DIBENAMINE PROTECTION AGAINST CYCLOPROPANE-EPINEPHRINE CARDIAC ARRHYTHMIAS

¹ Department of Pharmacology, University of Utah School of Medicine, Salt Lake City, Utah

Experiments on dogs under cyclopropane anesthesia indicate that the protection against epinephrine-induced cardiac arrhythmias afforded by Dibenamine and related adrenergic blocking agents is due to two factors:

1. A direct cardiac action which requires larger doses of blocking agent than are necessary to reverse completely the peripheral pressor effect of the injected epinephrine. This protection is largely independent of a transient "quinidine like" action on the myocardium shared by related compounds devoid of adrenergic blocking activity.

2. Prevention of an elevated blood pressure during the period of epinephrine action. Artificial elevation of the blood pressure by occlusion of the thoracic aorta has been shown to act as an added stress capable of producing irregularities in many hearts otherwise protected by Dibenamine. The effects of aortic occlusion were found to be dependent upon the final level of systemic arterial pressure attained and to be largely independent of the magnitude of the rise in pressure. Sustained pressure elevation produces cumulative effects.

The heart was found to be most prone to develop arrhythmias shortly after the injected epinephrine first reaches it rather than at the time of maximum epinephrine rine concentration in the blood stream.

The influence of systemic arterial pressure on the production of cardiac arrhythmias does not appear to be mediated through the vagi.

The development of a relative myocardial hypoxia and the production of some degree of cardiac dilatation are discussed as possible mechanisms by which systemic hypertension might sensitize the myocardium to epinephrine-induced arrhythmias.

This article has been cited by other articles:

				W. J. Angenent and G. B. Koelle The Destruction of Epinephrine by the DOPA-Oxidase System of Ocular Tissue Science, November 14, 1952; 116(3020): 543 - 544. [PDF]

				J. H. Heller, R. B. Setlow, and E. Mylon Fluorescence of Mixtures of Arterenol, Epinephrine, and Phosphate Science, July 21, 1950; 112(2899): 88 - 89. [PDF]