Abstract: AIM: To investigate the long-term changes of heart function and ultrastructure after catheter-based transendocardial injection of naked DNA encoding vascular endothelial growth factor (VEGF) into ischemic porcine myocardium. METHODS: Thirty pigs were divided into control group (n=15) and VEGF group (n=15), and their left anterior descending coronary arteries were embolized by coronary artery balloon angioplasty. Constructed pIRES2-EGFP-hVEGF165 eukaryotic expression plasmid or blank plasmid was directly injected into the porcine ischemic myocardium through transendocardial injection catheter using NOGA system. Ultrasonography was used to detect the M-mode motion, cycle variation of integrated backscatter (CVIB) and left ventricular ejection fraction (LVEF). One year later, the animals were sacrificed to observe the capillary formation and ultrastructure in myocardial tissue by factor VIII strepto-avidin-biotin complex (SABC) staining and electronography, respectively. RESULTS: One year after the gene injection, M-mode motion, CVIB and LVEF showed a significant increase (P<0.05) and factor VIII SABC staining showed a significant increase in the number of capillaries ［(13±5)/HP vs. (38±5)/HP, P<0.01］ in the VEGF group compared with those in the control group. Electronography showed that myocardium atrophy (remaining myocardium in infarcted zone), myofilament fracture and mitochondrial degeneration (in ischemic zone) were heavier in the control group compared with those in the VEGF group. CONCLUSION: Transendocardial injection of naked DNA encoding VEGF into ischemic porcine myocardium increases capillary number, recovers local myocardial structure and increases heart function.