摘要
目的 揭示咪达普利 (imidapril)抑制扩张型心肌病 (DCM)患者发生室性心律失常的机制。方法用多柔比星制备家兔DCM模型 ,咪达普利 1.2 5mg·kg- 1·d- 1po ,连续 8周进行干预。取心脏分离左室游离壁三层心肌细胞 ,全细胞膜片钳技术记录L 型钙电流 (ICa L)。结果 由于DCM模型心肌细胞的膜电容增加 ,所以ICa L密度明显减少 ,心外膜下心肌、中层心肌和心内膜下心肌分别为 ( 6 .7± 1.0 ) ,( 10 .6± 0 .5 )和 ( 7.4± 0 .7)pA·pF- 1,各层细胞间电流密度差异加大。咪达普利处理后可逆转心肌的病变 ,ICa L的密度明显高于DCM组 (P <0 .0 5 ) ,心外膜下心肌、中层心肌和心内膜下心肌分别为 ( 10 .3±1.0 ) ,( 12 .7± 0 .6 )和 ( 11.1± 1.6 )pA·pF- 1,使三层细胞间电流密度差异减小。结论 咪达普利可逆转DCM后心肌细胞ICa L的改变 ,减少跨室壁差异。提示可能是其减少DCM后发生快速心律失常的机制之一。
AIM To explore the mechanism of imidapril inhibition on ventricular arrhythmia in patients with dilated cardiomyopathy(DCM). METHODS DCM model in rabbits was induced with doxorubicin, and imidapril 1.25 mg·kg-1·d-1 was orally administered for 8 weeks. Subendocardium(Endo), midmyocardium(M) and subepicardium(Epi) were isolated from the left ventricular free wall in rabbits. ICa L was recorded with whole cell patch clamp technique. RESULTS With the increment of cellular membrane capacitance in DCM cells, ICa L densities decreased markedly. The average ICa L densities of Epi, M and Endo in DCM cells were (6.7±1.0), (10.6±0.5 ) and (7.4±0.7)pA·pF-1. The difference of ICa L densities from three layer cells was obviously increased. After treatment with imidapril, the ICa L densities of Epi, M and Endo increased to (10.3±1.0), (12.7±0.6) and (11.1±1.6)pA·pF-1. Furthermore, the diversity of ICa L densities of Epi, M and Endo was reduced. CONCLUSION Imidapril can decrease transmural variations of calcium current of ventricular in rabbits of DCM, which may be one of the mechanisms of antiarrhythmias.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2004年第3期194-198,共5页
Chinese Journal of Pharmacology and Toxicology
关键词
咪达普利
心肌病
充血性
心肌
钙通道
膜片钳技术
全细胞
imidapril
cardiomyopathy, congestive
myocardium
calcium channels
patch clamp technique, whole-cell
