Lopaschuk G D, McNeil G F, McVeigh J J
Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Mol Cell Biochem. 1989;88(1-2):175-9. doi: 10.1007/BF00223440.
The effect of the carnitine palmitoyltransferase 1 (CPT 1) inhibitor, Etomoxir, on glucose oxidation rates was determined in ischemic hearts reperfused in the presence of fatty acids. Isolated working rat hearts were perfused with 11 mM (14C)-glucose and 1.2 mM palmitate at a 15 cm H2O preload, 80 mm Hg afterload. Hearts were subjected to either 60 min aerobic perfusion, or 15 min work followed by 25 min global ischemia then 60 min of aerobic reperfusion. Steady state glucose oxidation rates in reperfused ischemic hearts were not significantly different from non-ischemic hearts. If 10(-9) M Etomoxir was added immediately prior to reperfusion no significant change in glucose oxidation occurred. Addition of 10(-8) M and 10(-6) M Etomoxir, however, significantly increased glucose oxidation. Etomoxir also significantly improved recovery of mechanical function at a concentration of 10(-8) M or greater. As we previously reported, no significant improvement of function was seen when 10(-9) M Etomoxir was added to the perfusate (Lopaschuk GD et al., Circ Res 63: 1036-1043, 1988). Long chain acylcarnitine levels were significantly reduced in the presence of both 10(-9) M and 10(-8) M Etomoxir. These data demonstrate that the beneficial effect of Etomoxir on reperfusion recovery of ischemic hearts is not due to a lowering of long chain acylcarnitine levels. Etomoxir may improve recovery of function by overcoming fatty acid inhibition of glucose oxidation.
在存在脂肪酸的情况下，对缺血再灌注心脏测定肉碱棕榈酰转移酶1（CPT 1）抑制剂依托莫西对葡萄糖氧化速率的影响。将离体工作的大鼠心脏在15 cm H2O前负荷、80 mmHg后负荷下用11 mM（14C）葡萄糖和1.2 mM棕榈酸酯灌注。心脏接受60分钟的有氧灌注，或15分钟的工作，随后25分钟全心缺血，然后60分钟有氧再灌注。再灌注缺血心脏中的稳态葡萄糖氧化速率与非缺血心脏无显著差异。如果在再灌注前立即加入10^(-9) M依托莫西，葡萄糖氧化无显著变化。然而，加入10^(-8) M和10^(-6) M依托莫西可显著增加葡萄糖氧化。依托莫西在浓度为10^(-8) M或更高时也显著改善了机械功能的恢复。正如我们之前报道的，当向灌注液中加入10^(-9) M依托莫西时，未观察到功能有显著改善（Lopaschuk GD等人，《循环研究》63: 1036 - 1043，1988）。在10^(-9) M和10^(-8) M依托莫西存在的情况下，长链酰基肉碱水平显著降低。这些数据表明，依托莫西对缺血心脏再灌注恢复的有益作用并非由于长链酰基肉碱水平的降低。依托莫西可能通过克服脂肪酸对葡萄糖氧化的抑制作用来改善功能恢复。
