Adriamycin cardiomyopathy in the rabbit: alterations in contractile proteins and myocyte function

Publisher Website
Google Scholar
Abstract
Study objective – The aim was to determine the mechanism of the cardiotoxic effect of adriamycin, particularly at the level of the function of the cardiac myocyte. Design – After chronic exposure to adriamycin, the contractile responses of single isolated cardiac myocytes to increasing calcium and isoprenaline were measured, as well as oxygen consumption of myocyte suspensions. Creatine kinase and myosin isoforms were investigated in whole ventricle. The degree of fibrosis of the ventricle was quantified using histological methods. Subjects – 24 white male New Zealand rabbits were treated with adriamycin (1 mg·kg−1) twice a week for eight weeks, and allowed to recover for two weeks. There were 29 untreated controls. Six further rabbits were implanted with mini osmotic pumps delivering a constant infusion of isoprenaline for one week; five controls had pumps containing saline. Measurements and main results – Cardiac myocytes were enzymatically isolated, and their contraction amplitude and velocity monitored. Cells isolated from adriamycin treated rabbits had a lower contraction amplitude than those from controls when maximally activated with calcium, at 11.1(0.9)% shortening(n = ll) ν 13.6(0.5)%(n = 14), p6 cells was lower in preparations from treated animals (p−1 wet tissue, n = 4, in controls to 5.76(1.55) mg·g−1, n = 6, in adriamycin treated animals (pConclusions – Single cardiac myocytes isolated from the hearts of adriamycin treated rabbits show a decrease in contraction amplitude, velocity, and oxygen consumption compared to controls. The decreased contractility of individual myocytes may relate to their low myosin content, and could contribute to the reduced cardiac output produced by adriamycin treatment. Heart failure induced by adriamycin in the rabbit is not accompanied by p adrenoceptor desensitisation.