Localization of the neurally mediated coronary vasoconstrictor properties of digitalis in the cat.

Abstract

SUMMARY Neural activation by digitalis has been shown to facilitate the development of cardiac arrhythmias and to mediate digitalis-induced increases in systemic and coronary resistance. Recent studies in our laboratory have implicated an area in the medulla within 2 inn of the obex as the locus for the neurally mediated arrhythmogenic properties of digitalis. To localize the site of digitalis-induced neural activation leading to increased coronary vascular resistance, 56 cats were anesthetized and an electromagnetic flow probe placed around the proximal right coronary artery. We used measurements of mean coronary flow and mean central aortic pressure and determined mean coronary vascular resistance every 6 minutes. DIGITALIS is well known to have a vasoconstrictor effect on the systemic arterial, venous, and splanchnic circulations (Ross et aL, 1960;Mason et al., 1964;Harrison et al., 1969;Katz et al., 1978). The rise in coronary vascular resistance in response to rapidly administered cardiac glycosides has been demonstrated to be mediated, in part, by the central nervous system (Vatner et al., 1971;Garan et al., 1974). Vatner et al. (1971) demonstrated that ouabain caused a rise in coronary vascular resistance in dogs when injected intravenously at a dose of 20 /ig/kg. This study and that of Hamlin et al. (1974) demonstrated a neurogenic component in the coronary vasoconstrictor effects of digitalis that could be abolished by a-adrenergic receptor blockade using phenoxybenzamine. Cross-perfusion experiments, in which the isolated head of an operative dog was perfused with digoxin-containing blood from a donor dog, thus keeping digoxin levels in the remainder of the operative dog very low, showed a degree of coronary vasoconstriction in the operative From the Cardiovascular Division,

Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity

“…It has been reported by many authors (48,49,22,34) that ouabain will induce arrhythmias. This is seen in both control and hypertensive animals in Figure 3 and in the timing data presented in Tables 3 and 4.…”

“…This induction of ventricular rhythm disorders by ouabain and other cardiac glycosides has been assumed to result solely from the direct action of these drugs on myocardial cell membranes (1,41,43,18,20). Recent studies have shown that the central nervous system, via autonomic efferents, plays a major role in the induction of ventricular rhythm disorders by digitalis (38,15,10,47,48). An increase in sympathetic nerve traffic toward the heart invariably accompanies electrocardiographic evidence of digitalis-induced rhythm disorders in experimental animals (10,47,48).…”

“…Recent studies have shown that the central nervous system, via autonomic efferents, plays a major role in the induction of ventricular rhythm disorders by digitalis (38,15,10,47,48). An increase in sympathetic nerve traffic toward the heart invariably accompanies electrocardiographic evidence of digitalis-induced rhythm disorders in experimental animals (10,47,48).…”

Ouabain‐Induced Coronary Vasoconstriction In Cats Is Not Neurally Mediated

“…It has been widely assumed that coronary constriction to digitalis glycosides results from central sympathetic activation 18,19,20,25,26 . Attempts have been made to localize the neurogenic site through which ouabain acts 19,20,27,28 .…”

“…Although coronary vasoconstriction to digitalis includes a direct mechanism, 17 some studies suggest a primary role for central activation in digitalis‐induced coronary vasoconstriction 18,19 . Specifically, the area postrema, which is primarily responsible for the arrhythmogenic and emetic effects of digitalis, has been implicated as critical for the coronary constriction to systemically administered digitalis 20 .…”