Sympathetic Neural Remodeling After Myocardial Infarction And Its Relation With The Growth Associated Protein-43

Sudden cardiac death (SCD) from any cause claims 300,000-400,000 lives a year in the United States. The most common sequence of events leading to SCD appears to be ventricular tachycardia (VT) and ventricular fibrillation (VF). 80 percent of them have coronary artery diseases. The alternation of sympathetic nerve density (sympathetic remodeling) was found in many cardiac diseases recently. The density of these sympathetic nerves directly correlates with the occurrence of life-threatening ventricular arrhythmia. The aim of this study is to explore the expression of growth associated protein-43 (GAP-43) and its effect on neural remodeling after myocardial infarction(MI) in rabbits and the effect ofβ-blocker on neural remodeling.METHODS Samples were obtained from the MI rabbits in peri-infarcted area, ventricular septum and right ventricle(RV). By immunohistochemistric method and computer image processing technique, the expression of GAP-43 and the density and extent of sympathetic innervation were examined in different groups(3 days,7 days,30 days after MI and propranolol taken orally).Results: In the 3-day group,the expressions of GAP-43 were significantly higher in peri-infarcted area and higher in RV and ventricular septum than those in the control areas (P<0.01) , the density of sympathetic nerve decreased in peri-infarcted area and ventricular septum (P<0.01)but increased in RV significantly(P<0.01) , and GAP-43 expression correlated with sympathetic innervation in RV(P<0.01).In the 7-day group,the expressions of GAP-43 and density of sympathetic nerves in peri-infracted area,ventricular septum and RV were significantly increased(P<0.01). GAP-43 expression is correlated with sympathetic innervation in peri-infarcted area(P<0.01).In the 30-day group,the expressions of GAP-43 decreased significantly in peri-infarcted area, ventricular septum and RV (P<0.01),the density and the extent of sympathetic nerve were higher than that in 3 and 7 day groups.Propranolol can decrease the density of sympathetic innervation in ventricular septum and RV(P<0.01), and normalize the extent of sympathetic innervation in the whole ventricle after left ventricular myocardial infarction. Conclusion: The expression of GAP-43 in myocardium was dynamic and correlated with the density and the extent of sympathetic innervation.β-blocker can play an important role in improving this sympathetic neural remodeling.