RESUMO
Objective To investigate the role of mitochondrial ATP-sensitive potassium(mito-KATP)channels in attenuation of ischemia-reperfusion(I/R)injury by lidocaine pretreatment in the isolated rat heart.Methods Adult female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3% pentobarbital 35 mg/kg.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2-5%CO2 at 37 ℃.Twenty-four isolated rat hearts with I/R injury were randomly divided into 3 groups(n = 8 each):group I/R,lidocaine group(group L)and lidocaine + glibenclamide group(group LG).After 10 min of equilibration,group C,L and LG received 20 min of perfusion with K-H solution,K-H solution containing lidocaine 2.5 mg/L and K-H solution containing lidocaine 2.5 mg/L + glibenclamide(a blocker of mito-KATP channels)10 μmol/L,respectively,then subjected to 30 min of ischemia followed by 60 min of reperfusion.HR,left ventricular developed pressure(LVDP),+ dp/dtmax and - dp/dtmax were recorded at the end of equilibration(T0)and at 15,30,45 and 60 min of reperfusion(T1-4).Coronary effluent was collected at T0 and T4 for determination of lactate dehydrogenase(LDH)and creatine kinase(CK)activities.Myocardial tissues were obtained from cardiac apex at T4 for determination of Na+ -K+ -ATPase and SOD activities and MDA and Ca2+ contents.Results Compared with group I/R,HR,LVDP,+ dp/dtmax and - dp/dtmax were significantly increased,CK and LHD activities were decreased,Na+ -K+-ATPase and SOD activities were increased,and MDA and Ca2+ contents were decreased in group L(P ＜0.05).Compared with group L,HR,LVDP,+ dp/dtmax and -dp/dtmax were significantly decreased,CK and LHD activities were increased,Na+ -K+ -ATPase and SOD activities were decreased,and MDA and Ca2+ contents were increased in group LG(P＜0.05).Conclusion The mechanism by which lidocaine pretreatment attenuates I/R injury to the isolated rat heart is related to mito-KATP channel opening.
