Abstract: AIM: To investigate whether desipramine can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) in rats with induced acute myocardial ischemia and to study the relationship between sympathetic remodeling and VFT. METHODS: Sixty Sprague Dawley rats were randomly assigned into three groups. In the myocardial ischemia group, the left anterior descending coronary artery (LAD) was clamped for 30 min. In the desipramine group, 5 min prior to clamping, desipramine (0.8 mg/kg) was administered IV. In the sham-operated group, operation was performed on rats but without clamping the coronary artery. One week after the operation, VFT was measured and the distribution and density of growth-associated protein43 (GAP43) and tyrosine hydroxylase (TH)-positive nerve fibers in ventricle were detected by immunohistochemical techniques. GAP43 and TH mRNA expression levels in infarcted border zone were also measured by RT-PCR techniques. RESULTS: VFT of desipramine group (11.0±2.65)V was significantly higher than that in myocardial ischemia group (7.2±1.30)V (P<0.05), but no significant difference was found compared with that in sham-operated group (13.0±2.12)V. The distribution of nerve fibers in myocardial ischemia group was chaotic and the density was significantly higher than in the desipramine group and sham-operated group (P<0.05). Compared with those in myocardial ischemia group, GAP43 and TH mRNA expression levels in desipramine group decreased significantly (P<0.05). CONCLUSION: Desipramine improves sympathetic remodeling and increases VFT and electrical stability of ischemic hearts after acute myocardial ischemia.