Risk of Ventricular Arrhythmias after Myocardial Infarction with Diabetes Associated with Sympathetic Neural Remodeling in Rabbits

Abstract

Background: Abnormal sympathetic innervation underlies both long-term hyperglycemia and myocardial infarction (MI). The incidence of ventricular arrhythmias (VAs) after MI is higher in diabetic than in nondiabetic patients. However, the exact mechanism remains unclear. In this study, we aimed to explore sympathetic neural remodeling after MI in diabetic rabbits and its relationship with VAs. Methods: Rabbits were randomly assigned to 4 groups: control, diabetes mellitus (DM), MI and diabetic myocardial infarction (DI). After electrophysiological experiments in vivo, immunohistochemistry and real-time RT-PCR were used to measure sympathetic innervations. To test the function of sympathetic nerve fibers, norepinephrine levels were measured by high-performance liquid chromatography. Results: The corrected QT interval and QT dispersion were significantly more prolonged with DI than other conditions. The density of tyrosine hydroxylase-positive fibers and corresponding mRNA abundance was significantly higher with DI than with DM and under control conditions, but was lower than with the MI group. Moreover, the distribution and structure of regenerated nerve was heterogeneous in DI rabbits. Norepinephrine content was higher in the DI group, and accompanied by an increased quantity of tyrosine hydroxylase-positive fibers. Conclusion: MI results in sympathetic neural remodeling in diabetic rabbits, which may be responsible in part for the increased occurrence of VAs.