R-苯异丙基腺苷预适应抗缺血性室性心律失常的第二保护窗口

Antiarrhythmic Effect Mediated by Adenosine A_1 Receptor Agonist R-Phenylisopyladenosine on Ischemia-Induced Ventricular Tachyarrhythmias in Rats

目的 :观察腺苷A1受体激动剂R 苯异丙基腺苷 (R PIA)预治疗大鼠后 2 4小时 ,是否具有抗缺血性室性心律失常作用。 方法 :雄性Wistar大鼠 80只 ,随机分为 5组 :①生理盐水组 ( 0 2ml/只 ,皮下注射 ) ;②R PIA组 ( 0 0 3mg/kg ,皮下注射 ) ;③R PIA ( 0 0 3mg/kg ,皮下注射 ) +1,3 二丙基 8 环戊基黄嘌啉 (DPCPX ,0 2mg/kg ,皮下注射 )组 ;④R PIA( 0 0 3mg/kg ,皮下注射 ) +N 硝基 L 精氨酸 (L NNA ,5mg/kg ,腹腔内注射 )组 ;⑤R PIA ( 0 0 3mg/kg ,皮下注射 )+格列苯脲 (Gli,0 3mg/kg ,静脉注射 ,于缺血前 2 0min)组。动物给药后 2 4小时 ,开胸 ,结扎左冠状动脉前降支建立心肌缺血再灌注模型。应用Cardio 2心功能软件连续监测和分析左心室压力变化曲线、心律和心率变化 ,结合心电图分析缺血 30min内室性心动过速 (室速 )和心室颤动 (室颤 )的发生率、开始时间、持续时间。 结果 :①单因素方差分析 (ANOVA)结果显示 ,缺血前各组大鼠心律、心率和心脏功能组间比较无显著性差异 (P>0 0 5 ) ;②R PIA组心肌缺血 30min内室速和 (或 )室颤的发生率和持续时间与生理盐水组、R PIA +DPCPX组和R PIA +Gli组比较有非常显著性差异 (P <0 0 1)。

Objective:To investigate whether administration of adenosine A 1 receptor agonist (R-phenylisopropyladenosine,R-PIA)24 hours before coronary ligation has antiarrhythmic effects on ischemia-induced ventricular tachyarrhythmias in rats. Methods:Eighty male Wistar rats were randomly divided into five groups(n=16 for each)and given to each rat:①Subcutaneous normal saline 0.2*!ml;②Subcutaneous R-PIA 0.03 mg/kg;③Subcutaneous R-PIA 0.03 mg/kg and 1,3-dipropy1-8-cyclopentylxanthine(DPCPX)0.2 mg/kg;④Intraperitoneal R-PIA 0.03 mg/kg and N w-nitro-L-arginine(L-NNA)5 mg/kg;and ⑤Subcutaneous R-PIA 0.03 mg/kg 20 min previously to coronary ligation and intravenous glibenclamide 0.3 mg/kg.Twenty-four hours after pretreatment all the rats were opened and subjected to 30 min of regional myocardial ischemia by ligation of the left anterior descending coronary artery,and followed by 120 min of reperfusion.Left ventricular pressure curve and the rhythms and frequency of heartbeat were monitored and analysed by Cardio 2 soft ware.Combining left ventricular pressure curve with electrocardiogram,we analyzed the frequency,onset time and duration of ventricular tachycardia and fibrillation.The experimental data were processed by SPSS 8.0,followed by the q test and Chi-square test.The null hypothesis was rejected at p<0.05. Results:Single factor analysis of variance(ANOVA)revealed no significant difference in parameters of left ventricular function,rates and rhythms of heartbeat among groups before myocardial ischemia (p>0.05).During 30 minutes ischemia period,the frequency and duration of ventricular tachycardia and fibrillation in group R-PIA,were significantly reduced(p<0.01)compared with normal saline group;Adenosine A 1 receptor antagonist DPCPX or ATP-sensitive potassium channel antagonist glibenclamide could abrogate completely or partly blocked antiarrhythmic effect mediated by adenosine A 1 receptor agonist R-PIA pretreatment,but nitric oxide synthesis inhibitor L-NNA failed to weaken the effect of R-PIA. Conclusions:This study suggested that adenosine A 1 receptor agonist R-PIA pretreatment can offer delayed antiarrhythmic effect on ischemia-induced ventricular tachyarrhythmias.The mechanism may be associated with the opened ATP-sensitive potassium channels.