Myocardial adrenergic changes at two stages of heart failure due to adriamycin treatment in rats

Abstract

Changes in myocardial norepinephrine (NE) levels, turnover, uptake, and release in rats were examined at two stages of cardiac dysfunction induced by adriamycin (ADR) given intraperitoneally in six equal doses over a period of 2 wk for a cumulative dose of 15 mg/kg. At 3 wk posttreatment, ADR-treated animals showed no changes in left ventricular systolic pressure (LVSP), aortic systolic pressure (ASP), and aortic diastolic pressure (ADP) but left ventricular end-diastolic pressure (LVEDP) was significantly higher. At 6 wk posttreatment, LVSP, ASP, and ADP were significantly lower and LVEDP remained elevated. Animals in both ADR-treated groups showed signs of congestive heart failure as indicated by ascites, congestive liver, and elevated LVEDP. Structural changes typical of ADR cardiomyopathy were more pronounced in the 6-wk group. In vivo hemodynamic as well as in vitro muscle function response to different concentrations of epinephrine was depressed in its duration as well as extent in both 3- and 6-wk ADR-treated groups. Myocardial NE levels were increased in the 3-wk group but were depressed in the 6-wk group. NE turnover was faster in both 3- and 6-wk ADR groups, uptake was increased only in the 6-wk group, and release was unchanged. These data show increased cardiac sympathetic tone at both stages of ADR-induced congestive heart failure.