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

本文旨在探讨肌动蛋白稳定剂--鬼笔环肽(phalloidin)对心肌梗死(myocardial infarction,MI)大鼠离体心脏牵张所致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△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)]、单相动作电位复极90%的时程(monophasic action po-tential duration at 90%repolarization,MAPD 90)、室性期前收缩(premature ventricular beats,PVB)及室性心动过速(ventriculartachycardia,VT)发生率.结果显示,牵张使正常对照组及MI组大鼠MAPD 90明显延长(P<0.05,P<0.01),MI组大鼠MAPD 90延长更显著(P<0.05,P<0.01).鬼笔环肽(1 μmol/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MAPD90缩短(△V=0.3 mL时,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(均P<0.01).鬼笔环肽对正常大鼠心肌牵张后PVB、VT的发生率无显著影响,但使MI心肌PVB、VT的发生率明显下降(均P<0.01).MI组大鼠LVSP及 ap/dt max 较正常对照组显著降低(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后牵张加重恶性心律失常的发生和持续,鬼笔环肽可以明显抑制其发生.

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

The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiological characteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-two Wistar rats were randomly divided into 4 groups: control group (n=9), phalloidin 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 the stretch 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 mL separately 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 (MAPD90), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD(90) in both control and MI rats (P<0.05, P<0.01). Moreover, MAPD(90) in MI group increased more significantly than that in the control group at the same degree of stretch (P<0.05, P<0.01). Phalloidin (1 mumol/L) had no effect on MAPD(90) in basal state. After stretch, MAPD(90) in phalloidin group slightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD(90) in infarcted myocardium, especially when DV=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the control group (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and control group. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt(max) in MI group obviously decreased (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.