Liu Y, Downey J M
Department of Physiology, University of South Alabama, Mobile 36688.
Cardiovasc Res. 1993 Apr;27(4):608-11. doi: 10.1093/cvr/27.4.608.
Adenosine receptor antagonists and pertussis toxin both block the anti-infarct effect of preconditioning in rabbit heart. Because adenosine receptor blockers were found to have no effect against preconditioning in rat heart, a study was performed to test whether ribosylating G proteins with pertussis toxin would block the protection.
A branch of the left coronary artery was occluded for 30 min and reperfused for 2 h to produce infarction in open chest rats. Infarct size was assessed by tetrazolium staining. Pertussis toxin was given 48 h before surgery. Preconditioned rats experienced three cycles of 5 min regional ischaemia and 5 min reperfusion before the 30 min occlusion.
Four groups of rats were studied. Non-treated control rats had 68.8(SEM 2.2)% infarction of the risk zone and preconditioning reduced this to 32.0(6.5)%. Pertussis toxin completely eliminated the G protein mediated bradycardia caused by intravenous acetylcholine or adenosine infusion. Pertussis toxin treatment had no effect on infarct size in non-preconditioned rats [60.9(4.2)% infarction]. Preconditioning the pertussis toxin treated heart reduced infarction to 21.3(5.6)%, an amount comparable to that seen in non-treated rats. Arrhythmias during the 30 min ischaemia were reduced in preconditioned hearts and this protection was not altered by pertussis toxin treatment.
Preconditioning against either infarction or arrhythmias in the rat does not appear to involve a pertussis toxin sensitive G protein.
腺苷受体拮抗剂和百日咳毒素均可阻断兔心脏预处理的抗梗死作用。由于发现腺苷受体阻滞剂对大鼠心脏预处理无效,因此进行了一项研究以测试用百日咳毒素使G蛋白核糖基化是否会阻断这种保护作用。
在开胸大鼠中,将左冠状动脉的一个分支闭塞30分钟,然后再灌注2小时以产生梗死。通过四氮唑染色评估梗死面积。在手术前48小时给予百日咳毒素。预处理的大鼠在30分钟闭塞前经历了三个5分钟局部缺血和5分钟再灌注的循环。
研究了四组大鼠。未处理的对照大鼠梗死面积占危险区的68.8(标准误2.2)%,预处理后将其降至32.0(6.5)%。百日咳毒素完全消除了静脉注射乙酰胆碱或腺苷引起的G蛋白介导的心动过缓。百日咳毒素处理对未预处理大鼠的梗死面积没有影响[梗死面积为60.9(4.2)%]。对经百日咳毒素处理的心脏进行预处理可将梗死面积降至21.3(5.6)%,这一数值与未处理大鼠的相似。预处理的心脏在30分钟缺血期间的心律失常减少,并且这种保护作用不受百日咳毒素处理的影响。
大鼠对梗死或心律失常的预处理似乎不涉及百日咳毒素敏感的G蛋白。