31P NMR spectroscopy in chronic adriamycin cardiotoxicity

Abnormal cardiac energy metabolism has been postulated as a mechanism for adriamycin induced cardiotoxicity. This study was designed to determine high energy phosphate stores at rest and with hemodynamic stress in perfused rat hearts after animals had been chronically exposed to adriamycin (2 mg/kg weekly for 14 weeks). Morphologic and hemodynamic changes were mild in this model. Phosphorus-31 NMR determined intracellular pH and levels of inorganic phosphate (Pi) and ATP were comparable in treated and control hearts. Phosphocreatine (PCr) levels were markedly decreased in treated hearts (0.89 +/- 0.07 units/g versus 1.7 +/- 0.13 units/g, p less than 0.001). The PCr/Pi ratio decreased in both groups during hemodynamic stress. It recovered earlier in controls and there was a marked over-shoot after cessation of rapid pacing in this group which was not present in adriamycin treated hearts. These results suggest that metabolic regulation in response to hemodynamic stress is impaired after chronic adriamycin exposure. PCr depletion and delayed metabolic recovery after hemodynamic stress appear to be potentially useful markers for the effect of adriamycin on the heart.