左心室肥厚跨室壁电不均一性及缬沙坦对其影响的实验研究

Tansmural Repolarization Heterogeneity in Rabbits With Left Ventricular Hypertrophy and Effects of Volsartan on It

目的 :探讨肥厚心肌跨室壁复极不均一性及缬沙坦预防性给药的影响。方法 :家兔 30只 ,随机分为 3组 ,腹主动脉缩窄组 (缩窄组 )、假手术组、用药组。主动脉缩窄术制备家兔高血压心肌肥厚模型 ,胶原两步消化法分离获取左心室内膜、中层及外膜单个心肌细胞 ,以全细胞膜片钳技术记录单细胞跨膜动作电位和离子流。结果 :腹主动脉缩窄组外膜、中层、内膜 3层心肌细胞跨膜动作电位复极达 90 %时程 (APD90 )均较假手术组及用药组延长 ,有显著性差异 (P <0 0 5～ 0 0 1)。以中层心肌细胞延长最为明显 (延长比例 :中层 2 3% ,外膜 10 % ,内膜 8% ) ,使肥厚心肌跨室壁复极不均一性明显增大。用药组与假手术组间各层细胞跨膜动作电位复极达 90 %时程均无明显差异。缩窄组各层心肌细胞瞬时外向钾电流 (Ito)和延迟整流钾电流 (Iks)密度均较用药组及假手术组下降 ,有显著性差异 (P <0 0 5 ) ,以中层细胞下降的幅度最大 ,而用药组及假手术组间心肌细胞瞬时外向钾电流、延迟整流钾电流密度无显著差异。结论 :家兔心肌肥厚时中层心肌细胞跨膜动作电位复极达 90 %时程延长及心肌细胞瞬时外向钾电流、延迟整流钾电流下降较外膜和内膜细胞更为明显 ,使肥厚心肌跨室壁复极不均一性增大。缬沙坦预防性给药可抑制这一变化 ,?

Objective: To investigate the changes of repolarrization hetertogeneity across left ventricular wall in rabbits with cardiac hypertrophy and the effects of prophylactic treatment with volsartan. Methods: Ventricular hypertrophy was induced by a constriction of the abdominal aorta in rabbits. The single myocytes of epicardium, myocardium and endocardium were isolated enzymatically. Whole cell patch clamp technique was used to record the delayed rectifier potassium current(Iks),transient outward potassium current(Ito) and the action patential of the single myocytes. Results: The action potential duration at 90% repolarrization(APD 90 ) of epicardium, myocardium and endocardium were all significantly extended in hypertrophy group compared with the volsartan treat ment group and sham operation group.This prolongation of APD 90 was more pronounced in myocytes of myocardium than in those of epicardium and endocardium. The transmural repolarrization hetertogeneity was significantly increased in the hypertrophy group.The APD 90 in volsartan treat ment group was similar to that in the in sham operation group. The Iks and Ito density was significantly smaller in myocytes of epicardium,myocardium and endocardium in the hypertrophy group than to that in the volsartan treat ment group and the sham operation group.In the hypertrophy group the decrease of Iks and Ito density was more pronounced in myocardium than in epicardium and endocardium. Conclutions: The prolongation of APD 90 and reduction in Iks and Ito density are more pronounced in myocytes of myocardium than in those of epicardium and endocardium in rabbits with cardiac hypertrophy. Prophylactic treatment with volsartan can inhibit the changs.