Acute Energetic Effects of Daunomycin on Rabbit Heart Muscle

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Abstract
The acute effects of daunomycin on the mechanical and energetic outputs of rabbit papillary muscles were examined at 27.degree. C using a myothermic technique. Contrary to expectations, daunomycin, in concentrations ranging from 10-160 .mu.g/ml, acted as a positive inotropic agent in terms of peak stress development and work output. The rate of stress developent was, however, slightly depressed and the major mechanical effect of the drug prolonged the relaxation phase so that there were large drug-dependent increments in the stress-time integral. Daunomycin at a concentration of 80 .mu.g/ml produced a 22% increment in peak stress development and a 74% increment in stress-time integral. The linear relationship between total (active + passive) stress and heat production was altered such that there was a 73% increment in the activation heat component (intercept) and a 37% increase in the energy cost per unit stress development (slope). In afterloaded isotonic contractions, daunomycin increased the mean work output (W; averaged over all load levels) by 49%, but there was an even greater increment in the associated energy expenditure, ET, which rose by 66%. Consequently, the overall mechanical efficiency (W/ET .times. 100%) fell slightly. In the rabbit, daunomycin in the acute situation increases total Ca delivery to the myofilaments and decreases the apparent transduction efficiency. These acute effects are the opposite of those reported in papillary muscles taken from rabbits in cardiac failure induced by chronic daunomycin administration. The short-term effects of daunomycin in the rabbit differ substantially from those seen in the rat and guinea pig.