Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity

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Abstract
Previous studies have suggested that one of the mechanisms of adriamycin (ADR) cardiomyopathy is depletion of high-energy phosphate stores (HEP). To examine this hypothesis, we used 31P nuclear magnetic resonance to asses the adenosine triphosphate-to phosphocreatine ratio (ATP-to-PCR ratio) in Langendorff-Perfused rabbit hearts. Using either and acute (5 days of therapy at 5mg/kg /day) or chronic model (7 to 10 weeks of therapy at 1.2 or 1.5mg/kg twice a week) we compared isovolumetric LV systolic pressure, heart rate, ATP-to-PCR rations, and histologic lesions between the treated and control animals in each model. In the acute model, there was a significant incraease in the ATP-to-PCr ratio (P < 0.02), without significant change in myocardial function. Despite significant hemodynamic and histologic alterations in the chronic model, compared to controle, we were unable to identify significant differences in ATP-to PCr ratios. We conclude that (a) there appear to be differences in energy metablism between the acute cardiotoxicity and the chronic cardiomyopathy of ADR in the rabbit model and (b) the mechanism of the chronic cardiomyopathy from ADR therpy does not appear to be related to progressive impariment of cellular high-energy phosphate metabolims as measured by the ATP-to-PCr ratio. © 1986 Academic Press, Inc.