Refractory heart failure and age-related differences in adriamycin-induced myocardial changes in rats

Clinical use of adriamycin, an effective chemotherapeutic agent, has been restricted because of a demonstrated dose-limiting cardiotoxicity. To study age-related differences in adriamycin-induced cardiotoxicity, clinical status, developed force, ultrastructure, and lipid peroxide changes in the myocardium were investigated in two age groups of rats termed younger (Cy) and older (Co). Experimental animals (Cy + A; Co + A) received a cumulative dose of 15 mg/kg of adriamycin over 2 weeks. Animals in the Co + A group showed hydroperitoneum, higher mortality, and a greater decline in weight and feed consumption. Decline in base-line developed force in papillary muscles from Cy + A and Co + A group was not significant, but responsiveness to different interventions was attenuated. Papillary muscles from the Co + A group showed a significantly lesser increase over its control (Co) group in peak developed force in response to higher Ca2+. The decline in the peak developed force due to low Ca2+ and frequency increase was also significantly less in the Co + A group. Qualitatively similar but quantitatively less or even statistically insignificant changes were seen in the younger treated (Cy + A) group compared with its controls. A greater cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as the tubular system and accumulation of lipofuscin granules was seen in the Co + A group. While there was no significant change in the malondialdehyde content in the lipofuscin granules was seen in the Co + A group.(ABSTRACT TRUNCATED AT 250 WORDS)