山莨菪碱对兔缺血再灌注后心室肌细胞瞬间外向钾通道电流的影响

目的建立兔心肌缺血再灌注动物模型，研究山莨菪碱对兔在体缺血再灌注后心室肌细胞Ito的影响，探讨山莨菪碱抗再灌注心律失常的细胞学离子机制。方法45只新西兰大耳白兔随机分为3组：缺血再灌注动物模型组（I—R组，结扎冠脉左前降支30min后再开放120min），山莨菪碱治疗组（Ani组，手术前1min动物耳缘静脉注射山莨菪碱5mg／kg）和假手术对照组（只开胸不结扎血管）。观察缺血再灌注期间室性心律失常（室早、室速和室颤）的发生率及持续时间。采用酶解的方法分离缺血部位心室肌外膜单个心室肌细胞，应用全细胞膜片钳技术记录Ito结果与I—R组比较，Alli组兔室速、室颤发生率及持续时间明显下降，其心律失常的评分明显低于I—R组（2．6±0．7比3．6±0．8，P〈0．05）。对照组、I—R组和Ani组Ito电流密度（＋60mV时）分别为（17．41±3．13）pA／pF（n=15）、（9．49±1．91）pA／pF（n=11）和（16．55±2．86）pA／pF（n=10），I—R组与对照组相比显著下降（P〈0．01），Ani组与I—R组相比显著升高（P〈0．01）。结论山莨菪碱可降低心肌缺血再灌注期间心律失常的发生率。心肌缺血再灌注后Ito明显下降，山莨菪碱预处理可使下降的Ito上调，逆转电重构，可能为山莨菪碱降低心律失常发生率的细胞学离子机制。

Effects of anisodamine on transient outward potassium current in isolated ventricular myocytes from ischemia/reperfusion myocardium of rabbit

Objective This study sought to investigate the effects of anisodamine on transient outward potassium current （Ito） in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the cellular（ionic） basis of anisodamine treatment for antiarrhythmia. Methods Forty-five rabbits were randomly divided into three groups： ischemic-reperfusion group （I-R）, anisodamine imervention group （Ani） and sham-operated control group （CON）. Anesthetized rabbits were subjected to 30 min ischemia by ligation of the left anterior descending coronary artery and 60 min reperfusion. Ani group was injected with anisodamine at a dose of 5 mg/kg via femoral vein 1 min before operation. The incidence of ventricular arrhythmia was observed. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, Ani group and the same anatomy region in CON. Whole cell patch clamp technique was used to record Ito. Results Ani decreased the incidence and duration of ventricular arrhythmia by reperfusion compared with I-R group, resulting in significant decrease the scores of arrhythmia（2.6±0.7 vs 3.6±0.8 ,P〈0.05 ）. The Ito current density （at＋60 mV） was significantly decreased in I-R （9.49±1.91）pA/pF, n=11] compared with CON （17.41± 3.13）pA/pF, n=15, P〈0.01 ], while it was significantly increased in Ani group （16.55±2.86）pA/pF,n=10] compared with I-R group （P〈0.01）. Conclusion Anisodamine have the ability to reduce the occurrence of ventricular arrhythmia.Ischemia-reperfusion induced significant down-regulation of Ito, while pretreatment with anisodamine could attenuate this change, suggesting that anisodamine could reverse this electrical remodeling, which may be partly responsible for its antiarrhythmia effects.