Search

The intracardiac pathways carrying the cardiovascular reflex responses mediated by cardiac sympathetic and vagal afferent fibers were examined in this study. We investigated the response to epicardial applications of bradykinin (5 micrograms) and nicotine (50 micrograms) before and after regional epicardial applications of 85% phenol in chloralose anesthetized open-chest dogs. Bradykinin stimulated sympathetic afferents, while nicotine stimulated vagal afferents. Topical applications of phenol were used to interrupt these pathways. Before phenol encircling, bradykinin significantly increased--whereas nicotine significantly decreased--mean arterial blood pressure when applied at the same sites. After phenol, nicotine applied to all sites within and outside the phenol circle continued to decrease mean arterial pressure, whereas bradykinin applied to sites within the circle no longer increased mean arterial pressure. Removal of aortic and carotid baroreceptors did not significantly affect these responses. Painting horizontal stripes of phenol on the anterior and posterior left ventricular free wall basal to the site of bradykinin application eliminated the elevation in mean arterial pressure produced by bradykinin. Reapplication of bradykinin basal to the stripe restored its response. Phenol stripes eliminated the nicotine vasodepressor response only when the stripe was painted in the atrioventricular groove. When bradykinin and nicotine were injected via a nonocclusive intracoronary catheter, both drugs elicited an early depressor response (interrupted by vagotomy) and, in some animals a late pressor response (interrupted by stellectomy). Epicardial phenol encircling the flow distribution of the cannulated coronary artery interrupted most or all of the sympathetic afferents mediating pressor responses to bradykinin or nicotine, while leaving the depressor responses intact. The depressor responses were eliminated by applying phenol to the atrioventricular groove or by transecting the cervical vagi. These data suggest that sympathetic afferent fibers travel in the superficial subepicardium in an apex-to-base direction. Vagal afferent fibers travel deeper in the myocardium until they approach the atrioventricular groove, where they ascend to the superficial subepicardium.

To determine whether liposomes (microscopic phospholipid vesicles) may be useful in delivering drugs to a region of myocardial ischemia, we studied the concentration of positively charged and neutral liposomes containing 131I-albumin and horseradish peroxidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We studied the interaction of liposomes containing fluorescent dyes and horseradish peroxidase with isolated contracting cardiac myocytes. We found that positively charged and neutral liposomes accumulated in poorly perfused myocardium and that positively charged liposomes accumulated in the ischemic region to a greater extent than neutral liposomes [138 +/- 21 vs. 81 +/- 9% (mean +/- SE) of the concentration of liposomes in uninvolved myocardium]. Electron microscopic examination of this myocardium showed liposome contents to be located in the vascular space, in endothelial cells, and in ischemic myocytes. We found high potassium environment and that liposomal contents were scattered throughout the interior of the cells in the electron micrographs of some of the isolated myocytes. Anoxia alone for 20-30 minutes did not modify the liposome-isolated myocyte interaction or cause depolarization of the cells. We conclude that liposomes may be useful as drug carriers to depolarized ischemic myocardium, although significant uptake by normal myocardial cells cannot be expected with lecithin, cholesterol, and octadecylamine liposomes we used.

The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrograms, in open-chest dogs following acute coronary artery occlusion. We found that the degree of regional myocardial ischemia was related quantitatively to the reduction in amplitude recorded with bipolar electrograms in the subepicardium and subendocardium, and to the increase in duration of subepicardial electrograms. Other characteristics measured in electrograms did not relate to the degree of ischemia. Despite a comparable reduction in regional myocardial blood flow, subepicardial conduction delay exceeded that recorded in the subendocardium, which often exhibited accelerated conduction.