Takeo S, Tanonaka K, Tazuma Y, Miyake K, Murai R
Department of Physiology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
J Pharmacol Exp Ther. 1987 Dec;243(3):1131-8.
To elucidate possible mechanisms by which coenzyme Q10 enhances reoxygenation-induced recovery of cardiac contractile force after hypoxia, rabbit hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min-reoxygenation with or without pretreatment with coenzyme Q10. Hypoxia induced a decline in cardiac contractile force, a decrease in myocardial high-energy phosphates and a release of ATP metabolites and creatine phosphokinase from the perfused heart. Upon reoxygenation the rate of release of ATP metabolites subsided, but no appreciable recovery of the loss of contractile force and the reduction of myocardial ATP content was seen, and the release of creatine phosphokinase was increased further. Pretreatment of rabbits with coenzyme Q10 resulted in an appreciable recovery of cardiac contractile force and of myocardial ATP content upon reoxygenation. The release of creatine phosphokinase from hearts during hypoxia and reoxygenation was inhibited completely by the pretreatment. Changes in the UV absorbance of the perfusate suggested that coenzyme Q10 reduced the loss of ATP metabolites from hypoxic hearts. Furthermore, high-performance liquid chromatographic analysis indicated that coenzyme Q10 attenuated the release of inosine and hypoxanthine from the hearts and decreased myocardial inosine and adenosine content of the hypoxic heart, suggesting that coenzyme Q10 retards the breakdown of ATP metabolites which are possible substrates for a salvage synthesis of ATP, when oxygen is replenished. This could account for an appreciable restoration of ATP, and eventually provide a significant recovery of cardiac contractile force upon reoxygenation.
为阐明辅酶Q10增强缺氧后复氧诱导的心脏收缩力恢复的可能机制,对兔心脏进行20分钟的缺氧灌注,随后进行45分钟的复氧,复氧时分别使用或不使用辅酶Q10预处理。缺氧导致心脏收缩力下降、心肌高能磷酸盐减少以及ATP代谢产物和肌酸磷酸激酶从灌注心脏中释放。复氧时,ATP代谢产物的释放速率下降,但收缩力丧失和心肌ATP含量降低未见明显恢复,且肌酸磷酸激酶的释放进一步增加。用辅酶Q10预处理兔子后,复氧时心脏收缩力和心肌ATP含量明显恢复。预处理完全抑制了缺氧和复氧期间心脏中肌酸磷酸激酶的释放。灌注液紫外吸光度的变化表明辅酶Q10减少了缺氧心脏中ATP代谢产物的损失。此外,高效液相色谱分析表明辅酶Q10减弱了心脏中肌苷和次黄嘌呤的释放,并降低了缺氧心脏的心肌肌苷和腺苷含量,这表明辅酶Q10延缓了ATP代谢产物的分解,而这些代谢产物可能是补充氧气时ATP补救合成的底物。这可以解释ATP的明显恢复,并最终在复氧时使心脏收缩力显著恢复。