兔左室肥厚心肌跨室壁复极不均一性及其膜离子流变化的实验研究

Changes of transmural repolarization heterogeneity and ion currents in rabbits with left ventricular hypertrophy

目的探讨兔左心室肥厚心肌心外膜下、中层、心内膜下3层心肌细胞动作电位及膜离子流变化的不均一性。方法心肌肥厚组以腹主动脉缩窄术复制兔压力超负荷心肌肥厚模型,并设正常对照组以作比较。胶原酶两步消化法分离获取兔单个心室肌细胞,其中用植皮刀分离左室游离壁内膜下、中层、外膜下3层心肌。以全细胞膜片钳记录单细胞跨膜动作电位和离子电流。结果肥厚组3层心肌细胞动作电位时程(APD90)较对照组3层心肌细胞APD90均分别有明显延长,而以中层心肌细胞APD90延长最为明显(延长比例中层260%±27%,外膜140%±16%,内膜100%±11%),使肥厚心肌跨室壁复极不均一性明显大于对照组。肥厚组各层心肌细胞瞬时外向钾电流(Ito)和缓慢激活的延迟整流钾电流(IKs)密度均低于对照组,且均以中层细胞下降的幅度最大。肥厚组各层心肌细胞L型钙电流(ICa,L)与快速激活的延迟整流钾电流(IKr)密度与对照组均无明显差异。肥厚组各层心肌细胞内向整流钾电流(IK1)均明显低于对照组,但各层变低的幅度无明显差异。结论兔肥厚心肌跨室壁复极不均一性明显增大,Ito及IKs的跨室壁不均一性下降可能是其主要原因。

AIM: To investigate the changes of transmural repolarization heterogeneity and ion currents in rabbits with left ventricular hypertrophy. METHODS: Ventricular hypertrophy was induced by a partial constriction of the abdominal aorta in rabbits. Myocytes were isolated by a two steps enzymological method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from other region (midmyocardium, Mid) with a razor. Whole cell patch clamp technique was used to record the action potential and ion currents. RESULTS: The action potentials duration at 90% repolarization (APD 90 ) of Epi, Mid and Endo were all prolonged significantly in hypertrophy group compared to control group. This prolongation of APD 90 was more pronounced in Mid (26.0%±2.7%) than that in Epi (14.0%±1.6%) and Endo (10.0%±1.1%). The transmural repolarization heterogeneity was increased significantly in the hypertrophy group. The I Ks and I to density in Epi, Mid and Endo was decreased significantly in hypertrophy group compared to those in control group. This decrease in I Ks and I to density was more pronounced in Mid than in Epi and Endo. No significantly difference of I Ca,L and I Kr density between hypertrophy group and control group in three layers was observed. The I K1 density decreased significantly in hypertrophy group compared to control group, but the extent of the decrease had no differences among the three layers. CONCLUSIONS: The transmural repolarization heterogeneity increases significantly in rabbit hypertrophied ventricle. The decrease in transmural heterogeneity of I to and I Ks is the main causes. [