咪达普利对扩张型心肌病钙电流的跨室壁不均一性的影响

• 作 者: 李泱 邱萍 王琳 王士雯 钟江华 张存泰 陆再英
• 机 构: 解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,华中科技大学附属同济医院心内科,华中科技大学附属同济医院心内科,华中科技
• 出 处: 中国药理学与毒理学杂志
• 发表日期: 2004年03期
• 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

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。

Objective To reveal the mechanism of imidapril inhibiting ventricular arrhythmia in patients with dilated cardiomyopathy (DCM). Methods Doxorubicin was used to prepare rabbit model of DCM, with 155 mg · kg -1 · d -1 imidapril for 8 weeks. Left ventricular free wall myocardial cells were isolated from the heart and whole-cell patch-clamp technique to record L-type calcium current (ICa L). Results The density of ICa L was significantly decreased in the DCM model as compared with that in the DCM group (6.6 ± 1.0 and 6.6 ± 0.5, respectively) ) And (7.4 ± 0.7) pA · pF-1, the difference of current density between layers increased. Imidapril treatment could reverse the myocardial lesions, ICa L density was significantly higher than the DCM group (P <0.05), subepicardial myocardium, middle myocardium and subendocardial myocardium were (10.3 ± 1.0), (12.7 ± 0.6) and (11.1 ± 1.6) pA · pF-1, respectively. Conclusion Imidapril can reverse the change of ICa L in cardiac myocytes after DCM and reduce the transmural difference. It is suggested that it may be one of the mechanisms of DCM to reduce tachyarrhythmia.