Abstract 1272: Vascular Endothelium Growth Factor-165 Gene Therapy Promotes Cardiomyogenesis in Reperfused Myocardial Infarction
BACKGROUND: Vascular endothelial growth factor (VEGF) 165 has been found to promote cardiomyogenesis in chronic ischemia and non-reperfused myocardial infarction (MI).
HYPOTHESIS: VEGF-165 induces cardiomyogenesis in reperfused MI.
METHODS: 24 Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes of occlusion, and VEGF-165 gene therapy or placebo was administered. The viral vector Ad5-VEGF165 (2x1010 particles) consisted of a recombinant human adenovirus serotype 5, made replication deficient by replacement of the E1A/E1B genes by the human VEGF-165 gene. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n=6), IM placebo (n=6), IC Ad5-VEGF165 (n=6) and IC placebo (n=6). All pigs received bromo-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted 4 weeks post MI. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment.
RESULTS: In the groups receiving IM injections, the number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the VEGF group 64±28 vs placebo 16±26 (p=0.034). In the groups receiving IC infusions, the number of BrdU-labeled cardiomyocytes was not significantly different, VEGF 27±48 vs placebo 22±22 (p=0.81).
CONCLUSIONS: VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. Adenovirus mediated VEGF-165 gene transfer via direct IM injection was more effective than IC infusion.