Background: Neural remodeling is part of the pathophysiology of ventricular arrhythmias after myocardial infarction (MI). In this study, we developed a rabbit model of MI to investigate the effect of the beta-blocker metoprolol on ventricular neural remodeling and susceptibility to ventricular arrhythmias.
Methods: MI was induced by ligation of the left anterior descending coronary artery in 30 rabbits, and sham operations were performed in 12 control animals. Metoprolol was then administered to 15 of the MI animals. After electrophysiological recordings, the expression of nerve markers was studied at the infarct border and the non-infarct left ventricle free wall (LVFW) by immunostaining or RT-PCR.
Results: Eight weeks after MI, the incidence of inducible ventricular arrhythmias was significantly (P<0.01) higher in the MI group than in the sham group. However, metoprolol treatment decreased incidence of post-MI ventricular arrhythmias (8.3%) compared to those without treatment (58.3%, P<0.001). The density of nerve fibers was increased in MI group (3889+/-521 microm(2)/mm(2)) compared to the sham group (1727+/-304 microm(2)/mm(2)). Treatment of MI rabbits with metoprolol resulted in a partial reduction (2725+/-283 microm(2)/mm(2)). However, the shape and imbalance of nerve fibers appeared to be normalized by the metoprolol treatment. The expression levels of TH mRNA were reduced (P<0.01) by metoprolol treatment.
Conclusion: Metoprolol reduces post-MI ventricular arrhythmias, partly by altering the neural remodeling process.