Abstract 1251: Arrhythmogenesis Effect of Sympathetic Nerve Remodeling: The Contribution of Sympathetic Nerve Sprouting to Cardiac Structural and Electrical Remodeling

Abstract

Background: Sympathetic nerves are widely distributed in myocardium.Abnormal patterns of myocardial innervation are found in many cardiac disease. It is considered that sympathetic nerve sprouting plays an important role in arrhythmogenesis. However, mechanisms of inducing arrhythmia by sympathetic nerve sprouting are still unknown. Structural and electrical remodeling are basic arrhythmogenesis changes in patients suffer from ventricular arrhythmia. This study was designed to determine wether sympathetic nerve sprouting could induce structural and electrical remodeling.

Methods: Twenty rabbits were randomized into two groups. Sympathetic nerve sprouting was induced by injection of nerve growth factor (NGF7s) into myocardium, and sham operation served as control. Thirteen days after operation, all rabbits underwent electrophysiological test, the monophasic action potential duration at 90% repolarization(MAPD90) and ventricular effective refractory periods(VERP) were measured at three sites(interventricular septum, left free wall, left ventricular apex) on the epicardium. Immunocytochemical staining for Tyrosine hydroxylase(TH) and growth-associated protein-43(GAP43) were performed to study the density of sympathetic nerves. TNF-a level was measured by ELISA. Hydroxyproline content was estimated by alkaline hydrolysis method.

Results: Density of nerve fibers immunopositive to TH and GAP-43 was significantly higher in NGF group than control. NGF group manifested significant QTc prolongation (333.2±24.5ms versus 297.2±33.8ms, P<0.05), but didn’t show any increase in dispersion of MAP90 and VERP compared with control. Ventricular collagen content (0.58±0.13 versus 0.37±0.13 ug/mg, P<0.05) as well as TNF-a level (86.7±35.4 versus 33.1±9.5pg/mg, P<0.01) in NGF group increased significantly compared to control respectively.

Conclusions: Rabbits with cardiac sympathetic nerve sprouting manifested prolonged QTc interval, as well as higher expression of inflammation factor and increased collagen accumulation. The findings suggest that sympathetic nerve sprouting could contribute to proarrhythmia substrate formation by promoting cardiac structural and electrical remodeling.