Chatham J C, Cousins J P, Glickson J D
Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
J Mol Cell Cardiol. 1990 Oct;22(10):1187-97. doi: 10.1016/0022-2828(90)90082-d.
Acute adriamycin cardiotoxicity was studied in the isolated, perfused rat heart by 31P and 13C NMR spectroscopy at flow rates of 15 and 5 ml/min. Treated hearts received a total dose of 13.5 mg of adriamycin. 31P NMR spectra were collected at the beginning and end of each experiment, and cardiac function was recorded throughout. Hearts were perfused with [1-13C]glucose, and 13C NMR spectra were recorded in the presence and absence of the drug. At normal flow (15 ml/min), adriamycin caused a decline in cardiac function which was reversible when the drug was removed. There were no changes in high energy phosphate levels. The labeling of glutamate was unchanged in the presence of adriamycin; however, there was a slight increase in the labeling of lactate and alanine. At reduced flow (5 ml/min), control hearts exhibited a small decrease in ATP and phosphocreatine levels, and cardiac function was depressed. These changes were reversible when normal flow was restored. Nevertheless, adriamycin treatment at low flow caused an irreversible decline in function and in hydrolysis of ATP and phosphocreatine. At reduced flow, the control and drug-treated hearts showed similar labeling of the glutamate pool; however, there was significantly greater labeling of lactate and alanine during adriamycin treatment. These results indicate that adriamycin is more toxic under reduced flow conditions. Impairment of cardiac function by adriamycin without changes in glutamate labeling suggests that this drug alters the relationship between cardiac function and energy production.
通过31P和13C核磁共振波谱法，在流速为15和5毫升/分钟的离体灌注大鼠心脏中研究了急性阿霉素心脏毒性。处理过的心脏接受了总共13.5毫克的阿霉素剂量。在每个实验开始和结束时收集31P核磁共振波谱，并全程记录心脏功能。用[1-13C]葡萄糖灌注心脏，并在有和没有药物的情况下记录13C核磁共振波谱。在正常流速（15毫升/分钟）下，阿霉素导致心脏功能下降，当去除药物时这种下降是可逆的。高能磷酸盐水平没有变化。在阿霉素存在的情况下，谷氨酸的标记没有变化；然而，乳酸和丙氨酸的标记略有增加。在低流速（5毫升/分钟）下，对照心脏的ATP和磷酸肌酸水平略有下降，心脏功能受到抑制。当恢复正常流速时，这些变化是可逆的。然而，低流速下阿霉素处理导致功能以及ATP和磷酸肌酸水解出现不可逆下降。在低流速下，对照心脏和药物处理的心脏显示谷氨酸池的标记相似；然而，在阿霉素处理期间，乳酸和丙氨酸的标记明显增加。这些结果表明，在低流速条件下阿霉素毒性更大。阿霉素在不改变谷氨酸标记的情况下损害心脏功能，这表明该药物改变了心脏功能与能量产生之间的关系。
