缺血预处理对大鼠心脏的抗心律失常作用不涉及功能性Gi蛋白。

The antiarrhythmic action of ischaemic preconditioning in rat hearts does not involve functional Gi proteins.

作者信息

Lawson C S, Coltart D J, Hearse D J

机构信息

Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, United Kingdom.

出版信息

Cardiovasc Res. 1993 Apr;27(4):681-7. doi: 10.1093/cvr/27.4.681.

DOI:10.1093/cvr/27.4.681

PMID:8324805

Abstract

OBJECTIVE

Ischaemic preconditioning has been reported to be mediated by inhibitory G (Gi) proteins in rabbits; however, the mechanism of preconditioning in rats appears to differ from that in other species. The aim of this study was to determine whether functional Gi proteins are required for the antiarrhythmic action of preconditioning in rats.

METHODS

Donor rats were randomised to receive pertussis toxin (25 micrograms.kg-1 intravenously) or saline. After 48 h the hearts were isolated and Langendorff perfused with blood from untreated support rats. Cardiac rhythm was recorded continuously. Ischaemia and reperfusion were induced by occluding and releasing a snare around the left coronary artery. Following 10 min of aerobic perfusion hearts were further randomised to: (1) control groups (n = 12 per group) which underwent a further 30 min of aerobic perfusion, or (2) preconditioned groups (n = 12 per group) which were subjected to three cycles of 5 min of ischaemia and 5 min of reperfusion. All hearts subsequently underwent 30 min of regional ischaemia and 10 min of reperfusion during which arrhythmias were quantified.

RESULTS

In hearts not pretreated with pertussis toxin, preconditioning limited the severity of ischaemia induced arrhythmias. The incidence of ventricular tachycardia was reduced from 100% to 33% and the mean number of ventricular premature beats from 164(SEM 42) to 23(14) (each p < 0.05). Although pretreatment with pertussis toxin completely abolished the bradycardic response to both acetylcholine and adenosine (indicating functional blockade of Gi proteins), it did not significantly influence the degree of antiarrhythmic protection afforded by preconditioning. In pretreated hearts preconditioning reduced the incidence of ventricular tachycardia from 83% to 33% and the mean number of ventricular premature beats from 267(66) to 62(32) (each p < 0.05).

CONCLUSIONS

The antiarrhythmic action of preconditioning in isolated blood perfused rat hearts does not require functional Gi proteins.

摘要

目的

据报道，缺血预处理在兔中由抑制性G（Gi）蛋白介导；然而，大鼠预处理的机制似乎与其他物种不同。本研究的目的是确定功能性Gi蛋白对于大鼠预处理的抗心律失常作用是否必要。

方法

供体大鼠被随机分为接受百日咳毒素（25微克·千克-1静脉注射）或生理盐水。48小时后，分离心脏并通过Langendorff法用未处理的支持大鼠的血液进行灌注。连续记录心律。通过阻断和松开左冠状动脉周围的圈套器诱导缺血和再灌注。在有氧灌注10分钟后，心脏进一步随机分为：（1）对照组（每组n = 12），进行另外30分钟的有氧灌注，或（2）预处理组（每组n = 12），接受三个5分钟缺血和5分钟再灌注的循环。随后所有心脏进行30分钟的局部缺血和10分钟的再灌注，在此期间对心律失常进行量化。

结果

在未用百日咳毒素预处理的心脏中，预处理限制了缺血诱导的心律失常的严重程度。室性心动过速的发生率从100%降至33%，室性早搏的平均数量从164（标准误42）降至23（14）（每组p < 0.05）。虽然用百日咳毒素预处理完全消除了对乙酰胆碱和腺苷的心动过缓反应（表明Gi蛋白的功能被阻断），但它并未显著影响预处理提供的抗心律失常保护程度。在预处理的心脏中，预处理将室性心动过速的发生率从83%降至33%，室性早搏的平均数量从267（66）降至62（3）（每组p < 0.05）。