Liposome Concentration in Canine Ischemic Myocardium and Depolarized Myocardial Cells

To determine whether liposomes (microscopic phospholipid vesicles) may be useful In delivering drujfs to a region of myocardial igchemia, we studied the concentration of positively charged and neutral liposomes containing I-albumin and horseradish peroiidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We also studied the interaction of liposomea containing fluorescent dyes and horseradish peroiidaae 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 liposomew [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 that isolated cardiac myocytes avidly took up the liposomal contents when they were depolarized by a high potassium environment and that liposomal contents were scattered throughout the interior of the cells in electron micrographs of some of the isolated myocytefi. Anoxia alone for 20–30 minutes did not modify the liposome-isolated myoeyte 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 the lecithin, cholesterol, and octadecylamine liposomes we used.