卡维地洛对家兔心肌梗死慢性期梗死周边区交感神经重构和电重构的影响

Effect of carvedilol on sympathetic remodeling and electrical remodeling in infarcted border zone in the rabbit model of myocardial infarction

目的 研究卡维地洛对家兔心肌梗死慢性期梗死周边区交感神经重构和电重构的影响。方法 40只家兔随机分为两组：（1）心肌梗死组结扎冠状动脉前降支；（2）卡维地洛组结扎前降支并卡维地洛5mg·kg^-1·d^-1灌胃。8周后测量梗死周边区跨室壁复极离散度（TDR）、刺激交感神经时TDR、刺激交感神经引起TDR的变化（ATDR）及心室颤动（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）和酪氨酸羟化酶（TH）阳性纤维的分布和密度。结果 心肌梗死组梗死周边区心室肌神经分布紊乱，GAP43和TH染色阳性。卡维地洛组梗死周边区神经纤维密度较心肌梗死组显著降低（P〈0．01），其基础状态梗死周边区TDR、交感神经刺激时TDR和ATDR均较心肌梗死组显著降低（P〈0．01），室颤阈值明显提高（P〈0．01）。结论 卡维地洛可有效调整心肌梗死后神经重构，稳定电重构。

Objective To investigate effects of carvedilol on sympathetic remodeling and electrical remodeling in ventricle in infarcted border zone of rabbits after myocardial infarction （MI）. Methods Forty rabbits were randomly assigned into two groups ： MI group, ligation of the left anterior descending coronary artery ; carvedilol group, same operation as MI group, and administration of oral carvedilol 5 mg·kg^-1·d^-1 ×8 m beginning on the next day of operation. Eight weeks after surgery, transmural dispersion of ventricular repolarization （TDR） of baseline, TDR during sympathetic nerve stimulation, difference of TDR （ ATDR） during sympathetic nerve stimulation and ventricular fibrillation threshold （VFT） were measured in infarcted border zone. The distribution and density of growth associated protein 43 （ GAP43 ） and tyrosine hydroxylase （TH） in ventricle were also detected with immunohistochemical technique. Results In MI group, the distilbution of nerve fibers in infarcted border zone were chaotic and the fibers was immunoreactive to GAP43 and TH. Carvedilol decreased the density of sympathetic nerve, TDR of baseline, TDR during sympathetic nerve stimulation and ATDR （ P 〈 0. 01 ）, and raise VFT significantly （ P 〈 0. 01 ）. Conclusion Carvedilol may play an important role in regulating sympathetic remodeling and stabilizing electrical remodeling.