一氧化氮合酶抑制剂的抗心律失常作用

Antiarrhythmic Effects of Nitric Oxide Synthesis Inhibitor

目的 报道作者在大鼠冠状动脉缺血适应 (CIP)的L 精氨酸———一氧化氮机制的研究中的意外发现 ,提醒同道引以为戒。方法 雄性健康SD大鼠 80只 ,随机分为 4组 ,CIP组先给予反复 2次的左冠状动脉前降支 (LAD)结扎 5min后放开 5min的预处置 ,然后进行与对照 (NIP)组相同的LAD结扎 10min继之放开 10min的较长时间的缺血 -再灌注 (I R)处置。其他两组则于I R处置前分别静脉注射 10mg kg的L NNA(NIPLN组 )或L NAME(NIPLM组 )。多道生理记录仪联接微处理系统全程记录I R期间II导联心电图。结果 CIP组冠状动脉I R期的室性早搏 (VPBs)次数、阵发性室性心动过速 (VT)发作阵数 (TVT)和累计持续时间 (CDVT)、心室颤动 (Vf)发作阵数 (TVf)和累计持续时间 (CDVf)均较NIP组明显减少或缩短 (P <0 .0 1) ,动物死亡率由NIP组的 5 0 %下降为 0 (P <0 .0 5 )。NIPLN组和NIPLM组冠状动脉缺血期的TVT、CDVT、TVf、CDVf也较NIP组明显减少或缩短 (P <0 .0 5 ) ;再灌注期的TVT、TVf、CDVf也较NIP组明显减少或缩短 (P <0 .0 5 ) ;动物死亡率从NIP组的 5 0 %下降为 10 % (P =NS)。结论 大剂量非选择性NOS抑制剂L NNA和L NAME本身也有抗大鼠I R心律失常作用 ,作为工具用于大鼠I R心律失常保护作用有无L arg NO机制参与的研究需?

Objective We hope our colleagues enjoy our results that we surprizedly found that large dose (10 mg/kg) of n l nitro arginine (L NNA) or n L nitro arginine nethyl ester (L NAME) had the antiarrhythmic effects in anaesthetized rats when to determine whether the L arginine nitric oxide (L arg NO) pathway involved in the early antiarrhythmic effects of coronary artery ischemic preconditioning (CIP). Methods 80 healty male SD rats were randomly assigned to control(NIP),CIP,NIPLN and NIPLM groups.The treatment of primary long periods of ischemia and reperfusion (I R) on left anterior descending coronary artery (LAD) was given in NIP group.Before that treatment,repeated shirt periods of LAD ischemia and reperfusion,bolus L NNA (10 mg/kg) or L NAME (10 mg/kg) were given in other three groups respectively.Electrocardiogram (II lead ) was monitored and all arrhythmias were recorded.nonpaired t test and χ 2 test were used to evaluate the antiarrhythmic effects. Results Ventricular premature beats (VPBs),temporary ventricular tachiarrhythmias (TVT),temporary ventricular tachiarrhythmias(TVT),temporary ventricular fibrillations (TVf),cumulative duration of ventricular tachiarrhythmias (CDVT) and cumulative duration of ventricular fibrillations (CDVf) during I R were significantly reduced and shortened in group CIP than that in group NIP (all P<0.01).Mortality of rats was reduced from 50%(in group NIP) to 0(in group CIP).P<0.05.Similar results were observed in group NIPLN and NIPLM. Conclusions Our results suggested that large dose of non-selective nitric oxide syntheses inhibitor (e.g.L NNA,L NAME) suppressed the incidence of ischemia reperfusion induced arrhythmia.It should be caution to use it to determine the involvement of the L arg NO pathway in the antiarrhythmic effects.