Bittner V, Reeves R C, Digerness S B, Caulfield J B, Pohost G M
Division of Cardiovascular Disease, University of Alabama, Birmingham 35294.
Magn Reson Med. 1991 Jan;17(1):69-81. doi: 10.1002/mrm.1910170112.
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.
异常的心脏能量代谢被认为是阿霉素诱导心脏毒性的一种机制。本研究旨在确定动物长期暴露于阿霉素（每周2mg/kg，共14周）后，灌注大鼠心脏在静息状态和血流动力学应激状态下的高能磷酸储存情况。在该模型中，形态学和血流动力学变化较轻。磷-31核磁共振测定显示，处理组和对照组心脏的细胞内pH值以及无机磷酸盐（Pi）和三磷酸腺苷（ATP）水平相当。处理组心脏中的磷酸肌酸（PCr）水平显著降低（0.89±0.07单位/克 vs 1.7±0.13单位/克，p＜0.001）。在血流动力学应激期间，两组的PCr/Pi比值均降低。对照组恢复得更早，且在快速起搏停止后该组出现明显的过冲现象，而阿霉素处理的心脏中不存在这种现象。这些结果表明，长期暴露于阿霉素后，心脏对血流动力学应激的代谢调节受损。血流动力学应激后PCr耗竭和代谢恢复延迟似乎是阿霉素对心脏影响的潜在有用标志物。
