Taxol inhibits stretch-induced electrophysiological alterations in isolated rat hearts with acute myocardial infarction.
Mechanosensitive channels have been determined to work as transducers of mechanoelectric feedback in the heart, which is associated with the generation of arrhythmias. Recent studies have investigated the role of the cytoskeleton in ion channels control. This study explored the ability of taxol to inhibit stretch-induced electrophysiological alterations in the ischemic myocardium. Thirty-two Wistar rats were randomly divided into four groups: normal control group (n=9), taxol group (n=7), myocardial infarction (MI) group (n=9), and MI+taxol group (n=7). After Langendorff perfusion, the isolated hearts were stretched for 5 s by balloon inflation to 0.2 or 0.3 mL. The effects of stretching on 90% monophasic action potential duration (MAPD(90)), premature ventricular beats (PVB), and ventricular tachycardia (VT) were observed for 30 s. Stretching increased MAPD(90) in both the normal control and MI groups, but MAPD(90) increased more in the MI group for the same degree of stretch. Taxol (5 mumol L(-1)) had no effect on MAPD(90) under baseline, unstretched conditions, but MAPD(90) in the taxol group was slightly increased after stretching compared with the normal control group (P>0.05). However, taxol reduced MAPD(90) in infarcted myocardium (P<0.05 at DeltaV=0.3 mL). The incidences of PVB and VT in the MI group were higher than in the normal control group (both P<0.01). Taxol had no effect on the occurrence of arrhythmias in normal myocardium, but it inhibited PVB and VT in infarcted hearts (both P<0.01). Thus changes in MAPD and the occurrence of arrhythmias caused by mechanical stretching of the myocardium could be inhibited by taxol in isolated rat hearts during AMI, indicating the involvement of tubulin in mechanoelectric feedback in AMI.
Cao
JunXian
J
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Fu
Lu
L
Sun
DianJun
D
Xie
RongSheng
R
Zhou
Jue
J
Qu
Fan
F
D000818:Animals; D006321:Heart / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology*; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D017239:Paclitaxel