Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia

摘要

＜正＞ Aim:Overdoses of haloperidol are associated with major ventricular arrhythmias,cardiac conduction block,and sudden death.The aim of this experiment was tostudy the effect of haloperidol on the action potentials in cardiac Purkinje fibersand papillary muscles under normal and simulated ischemia conditions in rabbitsand guinea pigs.Methods:Using the standard intracellular microelectrodetechnique,we examined the effects of haloperidol on the action potential param-eters[action potential amplitude（APA）,phase 0 maximum upstroke velocity(Vmax),action potential amplitude at 90% of repolarization(APD90),and effective refrac-tory period（ERP）]in rabbit cardiac Purkinje fibers and guinea pig cardiac papillarycells,in which both tissues were under simulated ischemic conditions.Results:Under ischemic conditions,different concentrations of haloperidol depressed APAand prolonged APD90in a concentration-dependent manner in rabbit Purkinjefibers.Haloperidol（3μmol/L）significantly depressed APA and prolonged APD90,and from 1μmol/L,haloperidol showed significant depression on Vmax;ERP wasnot significantly affected.In guinea pig cardiac papillary muscles,the thresholdsof significant reduction in APA,Vmax,EPR,and APD90were 10,0.3,1,and1μmol/L,respectively,for haloperidol.Conclusion:Compared with cardiac con-ductive tissues,papillary muscles were more sensitive to ischemic conditions.Under ischemia,haloperidol prolonged ERP and APD90in a concentration-depen-dent manner and precipitated the decrease in Vmaxinduced by ischemia.Theshortening of ERP and APD90in papillary muscle action potentials may be inhibi-ted by haloperidol.