Cardiac energetics in daunorubicin-induced cardiomyopathy

Daunorubicin (DNR) 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 or exceeded 0.4. Mechanical, myothermic and polarographic measurements were made upon papillary muscles obtained from the right ventricle of DNR treated rabbits and their litter mate controls. DNR treatment significantly increased the PEP:LVET ratio (41%) and increased the left ventricular: body weight ratio (24%). Basal metabolism, measured 2 h after cardiectomy, was significantly reduced whether measured myothermically or polarographically: both measurements were highly correlated but the O2 consumption values were higher. Peak stress development was 31% lower in the DNR treated rabbits but this reduction was largely accounted for by a larger cross-sectional area (CSA) of the papillary muscles in this group. There was no change in the slope of the active heat: stress relationships but the stress-independent (activation) heat intercept was depressed. In isotonic studies DNR treatment caused a 57% reduction in work output per beat (relative to controls) and a 39% decline in active energy output. Because of the approximately parallel shift in work and total energy output mechanical efficiency was not significantly changed. It is suggested that part of the basal energy production fall produced by DNR relates to protein synthesis inhibition but that most of the other mechanical and energetic effects are probably explicable in terms of the intrinsic hypertrophic response of the 'failing' heart.