慢性压力超负荷左室电重构的异质性及离子基础

目的研究慢性压力超负荷左室电重构的异质性及离子基础。方法新西兰兔通过肾上腹主动脉次全结扎诱发左室慢性压力超负荷。采用全细胞膜片钳技术分别记录对照组及手术组左室内膜、中层及外膜细胞的动作电位,慢激活的延迟整流钾电流(IKs)及快激活的延迟整流钾电流(IKr)等。结果与对照组比较,基础周长为2s时,手术组左室内膜、中层及外膜细胞的动作电位复极90%的时程(APD90)分别延长27.7%、27.2%(P<0.05或0.01)、19.6%(P>0.05);对照组中层细胞的APD90较外膜细胞长50.8%,而手术组为60.4%;在测试电位为+50mV时,手术组左室内膜、中层及外膜细胞IKs尾电流密度分别减小26.1%、36.3%(P均<0.05)、23.0%(P>0.05);IKr尾电流密度分别减小31.7%、30.5%、30.0%(P<0.01或0.05)。对照组外膜细胞的IKs尾电流密度较中层细胞大49.1%,而手术组为77.6%;两组三层细胞之间IKr尾电流密度均无差别。结论正常兔左室存在跨壁复极异质性,心肌肥厚时进一步扩大,IKs分布及下调的不均一性是其离子流基础。

Heterogeneity of electrical remodeling and ionic basis in left ventricle with chronic pressure-overload

Objective To investigate the heterogeneity of electrical remodeling and ionic basis in left ventricle with chronic pressure-overload. Methods New zealand rabbits underwent subtotal banding of peritonial aorta to induce chronic pressure overload in left ventricle. Action potentials, slowly activating delayed rectifier potassium current ( IKs ) and rapidly activating delayed rectifier potassium current ( IKr ) were recorded in myocytes isolated from different layers of left ventricular free wall by using the whole-cell patch-clamp technique. Results At basic cycle length of 2 s, action potential duration of endocardial ( Endo ), midmyocardial ( Mid ), and epicardial ( Epi ) myocytes isolated from operation group increased by 27.7%,27.2%( P<0.05 or 0.01 ),19.6% (P>0.05 ) respectively; In control group, APD90 of Mid myocytes was 50.8% longer than that of Epi myocytes, in operation group which was 60.4%;At the test potential of 50 mV, IKs tail current density of Endo, Mid, and Epi myocytes in operation group decreased by 26.1%, 36.3% (P<0.05 ), 23.0% (P>0.05 ) respectively; IKr tail current density of Endo, Mid, and Epi myocytes in operation group decreased by 31.7% , 30.5% , 30.0% ( P<0.01 or 0.05 ) respectively. In control group, IKs tail current density of Epi myocytes was 49.1% bigger than that of Mid myocytes, in operation group, which is 77.6%. IKr tail current density had no significant difference among three layers in two groups. Conclusion Transmural repolarization heterogeneity, which exists in normal left ventricle of rabbit, is exaggerated in hypertrophic heart. Ununiform of distribution and down-regulation of IKs is ionic basis of this phenomenon.