【作者】 许佳俊；

【导师】 吴黎明； 陈良龙； 洪华山；

【作者基本信息】 福建医科大学 ， 内科学， 2004， 硕士

【摘要】 【目的】 观察不同浓度的吡那地尔( Pinacidil)预处理对在体兔缺血再灌注心室肌若干电生理参数的影响。【方法】 家兔32只,随机分为4组:即生理盐水+心室肌缺血再灌注组;吡那地尔预处理(浓度分别为0.2mg/kg、0.4mg/kg、0.8mg/kg)+心室肌缺血再灌注组,每组各8只。冠状动脉左前降支结扎前10分钟耳缘静脉注射吡那地尔,对照组于结扎前10分钟静脉注射等量的生理盐水。分别应用心外膜单相动作电位(MAP)记录法测定在体兔的心室肌在缺血期及再灌注期不同时段的MAP参数及S1-S2程控电刺激法测定心室颤阈(VFT)和心室易损期(VVP)等电生理指标的变化。【结果】 1、对心外膜MAP的影响:(1)应用吡那地尔后,即刻动作电位90%( APD90)及50%复极化时程(APD50)缩短;在缺血区,缺血30分钟与同时段的对照组比较,吡那地尔0.8mg/kg预处理组心室肌MAPD90、MAPD50分别缩短15.4%和31% (均P<0.05); (2) 缺血期及再灌注期,不同浓度吡那地尔预处理组均明显消除早期后除极(EAD);(3) 缺血期和再灌注期与同时段的对照组比较,吡那地尔0.2mg/kg预处理组能缩短心室肌缺血区与非缺血区MAPD90、MAPD50离散度(均P<0.05);吡那地尔0.2mg/kg预处理组与吡那地尔0.8mg/kg预处理组比较P<0.05,提示后者有增加缺血区与非缺血区MAPD90、MAPD50离散度的趋势。2、对VFT及VVP的影响:(1)在缺血期及再灌注期,与对照组比较吡那地尔0.2mg/kg预处理组可提高VFT、缩短VVP(P<0.05);(2) 在缺血及再灌注期,与同时段的对照组比较,吡那地尔0.8mg/kg预处理组对VVP及VFT影响不显著(P>0.05);(3)在缺血15分钟及再灌注即刻,与0.2mg/kg预处理组比较,0.8mg/kg<WP=4>吡那地尔预处理组有延长VVP、降低VFT的影响(P<0.05)。【结论】 一定浓度吡那地尔预处理能减轻家兔心室肌缺血再灌注所致触发性心律失常,其机制可能与减轻EAD有关;但若继续增加药物浓度则无明显抗心律失常,且呈恶化折返性心律失常趋势,此可能与其引起动作电位90%、50%复极时程过度缩短有关。KATP通道开放剂对缺血再灌注心律失常影响的二重性可能呈浓度依赖性。更多还原

【Abstract】 Objective: To investigate the effects of varied electrophysiological parameters with different concentration of pinacidil preconditioning on ventricular myocardium during ischemia and reperfusion period in rabbits.Methods: 32 anesthetized rabbits were randomly assigned into four groups: Saline+ ischemic reperfusion (IR) group (n=8); Pinacidil (0.2mg/kg or 0.4mg/kg or 0.8mg/kg) preconditioning + IR group, (n=8, respectively). Saline or pinacidil was injected intravenously before ten minutes of left anterior descending coronary artery (LAD) ligation in rabbits. Varied parameters of monophasic action potentials (MAPs) were recorded by monophasic action potentials techquie in vivo and S1-S2 programmed electrical stimulation (PES) method was employed to measure Ventricular fibrillation threshold (VFT) and ventricular vulnerable period (VVP).Results: 1. (1) MAPD90 and MAPD50 decreased immediately after pinacidil was given; Compared with that in control group, MAPD90 and MAPD50 of ischemia zone in pinacidil(0.8mg/kg) precontioning group were shortened by 15.4% and 31% after ischemia 30 minutes (P<0.05, respectively). (2) The pinacidil (0.2mg/kg、0.4mg/kg and 0.8mg/kg) preconditioning group can eliminate early afterdepolarization(EAD) on ventricular myocardium during ischemia and reperfusion period. (3) Compared with control group, pinacidil (0.2mg/kg) precontioning group could significantly decrease MAPD90d and MAPD50d between ischemic zone and no-ischemic zone during ischemia and reperfusion period (P<0.05); Pinacidil (0.8mg/kg) precontioning group could significantly increase MAPD90d and MAPD50d in contrast with pinacidil (0.2mg/kg) precontioning group (P<0.05).2. (1) Compared with control group, pinacidil (0.2mg/kg) preconditioning group could increase VFT and shorten VVP during ischemia and reperfusion period (P<0.05). (2)There was not statistically significant difference on VFT and VVP between pinacidil (0.8mg/kg) preconditioning group and control group during ischemia or reperfusion period (P>0.05). (3)Pinacidil (0.8mg/kg) preconditioning group can <WP=6>decrease VFT and prolong VVP compared with pinacidil (0.2mg/kg) preconditioning group (P<0.05).Conclusion: (1) The ischemia or reperfusion arrhythmias could be suppressed by pinacidil preconditioning and mechanism may relate to eliminate early afterdepolarization (EAD). (2) The higher concentration of pinacidil preconditioning trended to promote reentrant arrhythmia by shortened MAPD during ischemia period. (3) Dual characters of ATP-sensitive potassium channels opener on ischemia or reperfusion arrhythmia maybe have a relation with concentration -dependence.更多还原