美托洛尔和卡维地洛对心肌梗死后交感神经重构和电重构的影响

Comparison of the effect of metoprolol and carvedilol on sympathetic remodeling and electrical remodeling in infarcted border zone of rabbit after myocardial infarction.

目的比较美托洛尔和卡维地洛对家兔心肌梗死(简称心梗)慢性期梗死周边区交感神经重构和电重构的影响及差异。方法40只家兔随机分为两组,每组各20只,采用结扎左冠状动脉前降支(LAD)的方法制备心梗模型,美托洛尔组和卡维地洛组分别给予美托洛尔和卡维地洛各5 mg.kg-1.d-1灌胃。持续给药8周后分别测量梗死周边区基础状态下,刺激交感神经前后的单相动作电位(MAP),计算跨室壁复极离散度(TDR)和TDR的变化(ΔTDR);测定心室颤动(简称室颤)阈值。免疫组化法研究梗死周边区心肌中生长相关蛋白43(GAP43)和酪胺酸羟化酶(TH)阳性纤维的分布和密度。结果在基础状态下两组动物的TDR之间的差异无显著性,交感神经刺激时卡维地洛组的TDR和ΔTDR均较美托洛尔组显著降低(31.6±8.8 m s,5.8±11.2 m s vs 38.5±8.6 m s,13.3±3.0 m s,P均(0.01),室颤阈值提高(21.6±4.4 V vs 18.7±3.8 V,P(0.05);卡维地洛组梗死周边区神经纤维密度较美托洛尔组显著降低(GAP43:1 958.6±346.8μm2/mm2vs 2 549.9±553.7μm2/mm2,TH:1 417.7±252.6μm2/mm2vs 1 778.9±457.8μm2/mm2,P均(0.01)。结论卡维地洛比美托洛尔能更有效地抑制心梗后梗死周边区神经重构,改善电重构。

Objective To investigate the effects of metoprolol and carvedilol on sympathetic remodeling and electrical remodeling in the ventricle in the infarcted border zone （IBZ） of rabbits after myocardial infarction （MI）. Methods 40 rabbits were randomly assigned into two groups： Metoprolol group（ n = 20）, in which the left anterior descending coronary artery was ligated, and then Metoprolol 5 mg· kg^-1·d^-1 was given; Carvedilol group（ n =20） ,in which the operation was taken as the same in Metoprolol group, and Carvedilol 5 mg· kg^-1·d^-1 was given. Eight months after operation, monophasic action potential （MAP） of baseline, MAP , transmural dispersion of repolarization （TDR） and difference of TDR （ATDR） before and during sympathetic nerve stimulation and ventricular fibrillation threshold （VFT） were measured in IBZ. The distribution and density of growth associated protein 43 （ GAP43 ） and tyrosine hydroxylase （TH） in ventricle were also detected with immunohistochemical technique. Results There is no significance of TDR at baseline in two group, but the TDR and ATDR during sympathetic nerve stimulation were all shorter in Carvedilol group than Metoprolol group （31.6±8.8 ms, 5.8 ±11.2 ms vs 38.5 ±8.6 ms, 13.3 ±3.0 ms ,P 〈0.05）. VFT was higher in Carvedilol group than Metoprolol group （21.6 ± 4.4 V vs 18.7 ± 3.8 V, P 〈 0. 05 ）. The densities of GAP43 and TH positive nerves in the carvedilol group （ 1 958.6 ±346.8 μm^2/mm^2 and 1 417.7 ±252.6μm^2/mm^2, respectively） were lower than those in the Metoprolol group （2 549.9 ±553.7 μm^2/mm^2 and 1 778.9 ±457.8 μm^2/mm^2, respect tively, P〈0.01）. Conclusion Compared with Metoprolol, Carvedilol can inhibit sympathetic remodeling and electrical remodeling in IBZ more effectively after MI.