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鬼笔环肽对心肌梗死大鼠离体心脏牵张所致电生理学改变的影响

曹君娴, 富路, 谢荣盛, 李佳, 戴颖楠, 朱立群, 韩颖

哈尔滨医科大学附属第一医院心内三科.黑龙江,哈尔滨 150001

摘要

该文旨在探讨肌动蛋白稳定剂-----鬼笔环肽对心肌梗死(myocardial infarction, MI)大鼠离体心脏牵张时电生理学改变的影响。将32只Wistar大鼠随机分为正常对照组(n=9)、鬼笔环肽(phalloidin)组(n=7)、MI组(n=9)、MI +鬼笔环肽组(n=7)。离体心脏经Langendorff灌流后,通过改变水囊容积,以#DELTA#V=0.1、0.2、0.3 mL对心室牵张5 s,观察牵张后效应30 s,记录左心室内压力变化[左心室收缩压(left ventricular systolic pressure, LVSP)、左心室舒张末压(left ventricular end-diastolic pressure, LVEDP)、室内压最大上升/下降速率(±dp/dt_(max))]、90%单相动作电位时程(90% monophasic action potential duration, MAPD_(90))、室性期前收缩(premature ventricular beats, PVB)及室性心动过速(ventricular tachycardia, VT)。结果显示,牵张使正常对照组及MI组大鼠MAPD_(90)明显延长({sl P}<0.05, {sl P}<0.01),MI组大鼠MAPD_(90)延长更显著({sl P}<0.05, {sl P}<0.01)。鬼笔环肽(1 #mu#mol/L)对正常及MI心肌基础状态下的MAPD_(90)无影响,但使MI心肌牵张后已延长的MAPD_(90)明显缩短(#DELTA#V=0.3 mL时,{sl P}<0.05)。牵张后MI组大鼠PVB、VT的发生率明显高于正常对照组({sl P}<0.01)。鬼笔环肽使正常大鼠心肌牵张后PVB、VT的发生率略增加(无统计学意义),但使MI心肌PVB发生率明显下降,并显著抑制VT的发生率(均{sl P}<0.01)。MI组大鼠LVSP及+dp/dt_(max)较正常对照组显著降低({sl P}<0.01);鬼笔环肽可使MI心肌LVSP轻度回升,但无统计学意义。结果表明,MI后牵张更有助于恶性心律失常的产生和维持,鬼笔环肽可以明显抑制其发生。

关键词: 细胞骨架; 微丝; 机械-电耦联; 动作电位

Effect of phalloidin on electrophysiological changes induced by stretch of myocardial infarcted hearts in rats

Cao Junxian, Fu Lu, Xie Rongsheng, Li Jia, Dai Yingnan, Zhu Liqun, Han Ying

Department of Cardiology, the First Hospital of Harbin Medical University.Harbin 150001,Heilongjiang

Abstract

The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiologicalcharacteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-twoWistar rats were randomly divided into 4 groups: control group (n=9), phailoidin group (n=7), myocardial infarction (MI) group (n=9),MI + phalloidin group (n=7). The acute myocardial infarction (AMI) was conducted by ligation of the left anterior descending (LAD)coronary artery for 30 min in isolated rat heart. The volume alternation of a water-filled latex balloon in the left ventricle produced thestretch of myocardium. After perfused on Langendorff, the isolated hearts were stretched for 5 s by an inflation of 0.1, 0.2 and 0.3 mLseparately and the effect of stretch was observed for 30 s, including the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dt_(max), monophasic action potential duration at 90% repolarization (MAPD_(90)), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD_(90) in both control and MIrats (P<0.05, P<0.01). Moreover, MAPD_(90) in MI group increased more significantly than that in the control group at the same degreeof stretch (P<0.05, P<0.01). Phalloidin (1 #mu#mol/L) had no effect on MAPD90 in basal state. After stretch, MAPD_(90) in phalloidin groupslightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD_(90) in infarctedmyocardium, especially when #DELTA#V=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the controlgroup (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and controlgroup. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt_(max) in MI group obviouslydecreased (P<0.01 vs control). With application of phalloidin, LVSP slightly, but not significantly increased in infarcted hearts, while -dp/dt_(max) significantly increased (P<0.05). It is suggested that MI facilitates the generation and maintenance of malignant arrhythmias,while phalloidin obviously inhibits the occurrence of arrhythmias.

Key words: Cytoskeleton;microfilament;mechanoelectric coupling;Action potentials

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引用本文:

曹君娴, 富路, 谢荣盛, 李佳, 戴颖楠, 朱立群, 韩颖. 鬼笔环肽对心肌梗死大鼠离体心脏牵张所致电生理学改变的影响[J]. 生理学报 2008; 60 (2): 189-196.

Cao Junxian, Fu Lu, Xie Rongsheng, Li Jia, Dai Yingnan, Zhu Liqun, Han Ying. Effect of phalloidin on electrophysiological changes induced by stretch of myocardial infarcted hearts in rats. Acta Physiol Sin 2008; 60 (2): 189-196 (in Chinese with English abstract).