Daunomycin-induced cardiomyopathy in rabbits: Isolated heart and papillary muscle energetics

Abstract

Daunomycin was administered to one of each pair of litter mate rabbits at a weekly dosage rate of 40 mg/m2. Treated animals were killed when their pre-ejection period: left ventricular ejection time ratio (PEP:LVET) reached 0.4 and there was other evidence of cardiac abnormalities or when they had received 12 doses of daunomycin. Langendorff-perfused hearts from the treated animals had lower intrinsic heart rates (16%) and decreased coronary resistance (31%) in the arrested state. There was no significant difference between the basal metabolism of the arrested control and treated hearts but the magnitude of the activation component, measured under beating non-working conditions, was depressed by daunomycin. After the whole heart perfusion studies were complete, approximately 2 h after cardiectomy, papillary muscles were dissected out from the right ventricles and mechanical, myothermic and polarographic studies were undertaken. The resting heat production, in support of the whole heart metabolic data, was practically unchanged by the treatment regime. Peak stress development and work output were similar in both the control and treated groups. In energetic terms the slope of the relationship between total stress development and active heat production per beat was unchanged but there was a 21% depression of the activation heat component in the treated animals. Daunomycin treatment had not altered the work output per contraction or significantly changed energy output and hence mechanical efficiency was unaltered. It is clear that 2 h of Langendorff perfusion does not produce any depression of contractile or energetic properties in papillary muscles.