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Localization of the Neurally Mediated Coronary Vasoconstrictor Properties of Digitalis in the Cat

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. Coronary vascular resistance remained constant in control cats not receiving digitalis. Ouabain, 20 μg/kg, given intravenously, significantly increased coronary resistance for 40 minutes. Complete transaction of the neuraxls at the medullary level 2 mm above the obex failed to alter the rise in coronary resistance caused by ouabain. However, brainstem transection 2 mm below the obex completely abolished the rise in resistance caused by ouabain. a-Adrenergic blockade with phenoxybenzamine (0.5 mg/kg) In above-obex sectioned cats also abolished the ouabain-induced rise in coronary resistance. The administration of a highly polar cardiac glyoside, ASI-222, also produced a significant rise in coronary vascular resistance lasting 45 minutes, despite the fact that CSF samples obtained from the cisterna magna did not contain detectable levels of ASI-222. These studies indicate that an area of the medulla within 2 mm of the obex is involved in the mediation of the coronary vasoconstrictor properties of digitalis. These studies further implicate an area devoid of an effective blood brain barrier, and are consistent with the involvement of the area postrema in these vasoconstrictor effects.