Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity.
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 assess the adenosine triphosphate-to-phosphocreatine ratio (ATP-to-PCr ratio) in Langendorff-perfused rabbit hearts. Using either an acute (5 days of therapy at 5 mg/kg/day) or chronic model (7 to 10 weeks of therapy at 1.2 or 1.5 mg/kg twice a week), we compared isovolumetric LV systolic pressure, heart rate, ATP-to-PCr ratios, and histologic lesions between the treated and control animals in each model. In the acute model, there was a significant increase in the ATP-to-PCr ratio (P less than 0.02), without significant changes in myocardial function. Despite significant hemodynamic and histologic alterations in the chronic model, compared to controls, we were unable to identify significant differences in ATP-to-PCr ratios. We conclude that there appear to be differences in energy metabolism between the acute cardiotoxicity and the chronic cardiomyopathy of ADR in the rabbit model and the mechanism of the chronic cardiomyopathy from ADR therapy does not appear to be related to progressive impairment of cellular high-energy phosphate metabolism as measured by the ATP-to-PCr ratio.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011817:Rabbits
D010710:Phosphates; D010725:Phosphocreatine; D004317:Doxorubicin; D000255:Adenosine Triphosphate