Effects of Metoprolol on Sympathetic Remodeling and Electrical Remodeling at Infarcted Border Zone after Myocardial Infarction in Rabbits

Abstract

Background: The findings of sympathetic remodeling and its electrophysiological implications force us to rerecognize the drugs presently used. The aim of this study was toinvestigate the effects of metoprolol on sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) after myocardial infarction (MI). Methods: Forty rabbits were randomly assigned into two groups: MI group (n = 20), ligation of the anterior descending coronary; Metoprolol group (n = 20), ligation of the anterior descending coronary and administration of oral metoprolol 5 mg/kg/day. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, TDR and difference of TDR (ΔTDR) during sympathetic nerve stimulation were measured at the IBZ. The distribution and densities of growth associated protein 43 and tyrosine hydroxylase positive nerves at the IBZ were detected with immunohistochemical techniques. Results: The study was completed in the 36 surviving animals (18 rabbits in each group). The densities of growth associated protein 43 and tyrosine hydroxylase positive nerves in the Metoprolol group (2,550 ± 554 and 1,779 ± 458 µm²/mm², respectively) were lower than in the MI group (3,217 ± 589 and 2,616 ± 528 µm²/mm², respectively; both p < 0.01). TDR at baseline, TDR and ΔTDR during sympathetic nerve stimulation were shorter in the Metoprolol group than in the MI group (p < 0.01 for all). Conclusion: Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. The association of metoprolol with improved electrical remodeling may be partly related to the inhibition of sympathetic remodeling.