左旋体盐酸非洛普的抗实验性心律失常作用

Inhibitory effects of levo-phenoprolamine hydrochloride on experimental arrhythmias

目的 研究左旋体盐酸非洛普 [levo 1 (2 ,6 二甲基苯氧基 ) 2 (3 ,4 二甲氧基苯乙氨基 )丙烷盐酸盐 ,l DDPH对实验性心律失常的抑制作用。方法 iv哇巴因、乌头碱或氯化钙制造大鼠、豚鼠室性心律失常模型 ;标准微电极技术记录动作电位 ;全细胞膜片钳技术记录L型钙电流 (ICa,L)。结果 l DDPH 5 0mg·kg-1抑制哇巴因诱发的豚鼠室性心律失常以及乌头碱和氯化钙诱发的大鼠室性心律失常 ;l DDPH 3 0 μmol·L-1缩短豚鼠右心室乳头肌细胞 5 0 %动作电位时程 (APD50 )并延长有效不应期 (ERP) (n =6,P <0 0 5 ) ;l DDPH抑制单个豚鼠心室肌细胞ICa,L,其IC50 值为 12 9(95 %可信限 :7 0～ 18 8) μmol·L-1(n =5 )。结论 l DDPH具有抗实验性心律失常作用 ;其机制与抑制ICa,L、缩短APD50

AIM To investigate the effects of levo phenoprolamine hydrochloride [ levo 1 (2,6 dimethylphenoxy) 2 (3,4 dimethoxyphenyl ethylamino) propane hydrochloride] [ l DDPH([α]D 25 1 08)]on experimental arrhythmias. on experimental arrhythmias. METHODS Intravenous administration of ouabain, aconitine or CaCl 2 induced arrhythmias in rats or guinea pigs; Microelectrode recording was used to record action potential; Whole cell patch clamp technique was used to record L type calcium current ( I Ca,L ). RESULTS ① l DDPH 50 mg·kg -1 inhibited the ventricular arrhythmias induced by intravenous injection of ouabain in guinea pigs or aconitine and CaCl 2 in rats. ② l DDPH 30 μmol·L -1 shortened 50% action potential duration (APD 50 ) and prolonged effective refractory period (ERP) ( n =6, P <0 05) in guinea pig right ventricular papillary muscles. ③ l DDPH decreased I Ca,L in a dose dependent manner with an IC 50 value of 12 9(95% confidence limits:7 0～18 8) μmol·L -1 ( n =5) in single ventricular myocytes of guinea pigs. CONCLUSION l DDPH possessed antiarrhythmic characteristics; The possible mechnisms lied in its blocking effect on I Ca,L , shortening of APD 50 and the prolongation of ERP.