CAJ | 학술논문

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钠离子通道电流(I_(Na))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30 min后再开放120 min);山莨菪碱治疗组(Ani+I/R组,手术前1 min给予动物耳缘静脉注射山莨菪碱5 mg/kg);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I_Na.结果:(1) 心律失常发生率:与I/R组比较,Ani+I/R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 vs 3.6±0.8,P<0.05).对照组、I/R组和Ani+I/R组I_Na电流密度峰值(-30 mV)分别为-42.78± 5.48 (n=16)、-22.46±5.32 (n=12)和-38.89±5.24 pA/pF (n=13),I/R组明显低于对照组(P<0.01),Ani+I/R组明显高于I/R组(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,I_(Na)明显下降,山莨菪碱预处理可使下降的I_(Na)上调,逆转电重构,可能为山莨菪碱降低再灌注心律失常发生率的细胞学离子机制.
목적:건립토심기결혈재관주동물모형,연구산랑탕감대토재체결혈재관주후심실기세포납리자통도전류(I_(Na))적영향,탐토산랑탕감항재관주심률실상적세포학리자궤제.방법:45지신서란대이백토수궤분위3조:결혈재관주동물모형조(I/R조,결찰관맥좌전강지30 min후재개방120 min);산랑탕감치료조(Ani+I/R조,수술전1 min급여동물이연정맥주사산랑탕감5 mg/kg);가수술대조조(지개흉불결찰혈관).관찰결혈재관주기간실성심률실상(실조、실속화실전)적발생솔급지속시간.채용매해적방법분리결혈부위심실기외막단개심실기세포,응용전세포막편겸기술기록I_Na.결과:(1) 심률실상발생솔:여I/R조비교,Ani+I/R조토실속、실전발생솔급지속시간명현하강,기심률실상적평분명현저우I/R조(2.6±0.7 vs 3.6±0.8,P<0.05).대조조、I/R조화Ani+I/R조I_Na전류밀도봉치(-30 mV)분별위-42.78± 5.48 (n=16)、-22.46±5.32 (n=12)화-38.89±5.24 pA/pF (n=13),I/R조명현저우대조조(P<0.01),Ani+I/R조명현고우I/R조(P<0.01).결론:산랑탕감가강저심기결혈재관주기간심률실상적발생솔.심기결혈재관주후,I_(Na)명현하강,산랑탕감예처리가사하강적I_(Na)상조,역전전중구,가능위산랑탕감강저재관주심률실상발생솔적세포학리자궤제.
AIM: To investigate the effects of anisodamine on the sodium current (I_(Na)) 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 intervention group (Ani+I/R) 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. The animals in Ani group were 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+I/R group and the same anatomy region in CON. Whole cell patch clamp technique was used to record I_(Na). RESULTS: Anisodamine intervention decreased the incidence and duration of ventricular arrhythmia by reperfusion compared to I/R group, resulting in significant decrease in the scores of arrhythmia (2.6±0.7 vs 3.6±0.8, P<0.05). The peak I_(Na) current density (at-30 mV) was significantly decreased in I/R group (-22.46±5.32 pA/pF, n=12) compared to CON (-42.78±5.48 pA/pF, n=16, P<0.01), while it was significantly increased in Ani+I/R group (-38.89±5.24 pA/pF, n=13) compared to I/R group (P<0.01). CONCLUSION: Anisodamine has the ability to reduce the occurrence of ventricular arrhythmia. Ischemia-reperfusion induces significant down-regulation of I_(Na), while pretreatment with anisodamine attenuates this change, suggesting that anisodamine reverses this electrical remodeling, which may be partly responsible for its antiarrhythmia effects.