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

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Abstract
Neural activation by digitalis facilitates the development of cardiac arrhythmias and mediates digitalis-induced increases in systemic and coronary resistance. Recent studies in our laboratory have implicated an area in the medulla within 2 mm 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. Measurements of mean coronary flow and mean central aortic pressure were used to determine mean coronary vascular resistance every 5 min. Coronary vascular resistance remained constant in control cats not receiving digitalis. Ouabain, 20 .mu.g/kg, given i.v., significantly increased coronary resistance for 40 min. Complete transection of the neuraxis at the medullary level 2 mm above the obex failed to alter the rise in coronary resistance caused by ouabain. Brainstem transection 2 mm below the obex completely abolished the rise in resistance caused by ouabain. .alpha.-Adrenergic blocked blockade with phenoxybenzamine (0.5 mg/kg) in above-obex sectioned cats abolished the ouabain-induced rise in coronary resistance. The administration of a highly polar cardiac glycoside, ASI-222 [3-.beta.-O-(4-amino-4,6-dideoxy-.beta.-D-galactopyranosyl)digitoxigenin], produced a significant rise in coronary vascular resistance lasting 45 min, despite the fact that CSF samples obtained from the cisterna magna did not contain detectable levels of ASI-222. 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.