Combined intramyocardial plasmid-mediated VEGF165 gene transfer and intravenous erythropoietin in sheep with reperfused myocardial infarction

OLEA FD; CABEZA MECKERT P; CUNIBERTI L; DE LORENZI A; CORTES C; VERA JANAVEL G; BERCOVICH A; CRISCUOLO M; LAGUENS R; CROTTOGINI A

Ciudad Autónoma de Buenos Aires

Congreso; XVII Meeting International Society for Heart Research Latin American Section; 2009

International Society for heart Research

Reducing the size of reperfused (R) acute myocardial infarction (AMI) is an important task. We have shown that the intra-myocardial injection of a plasmid encoding VEGF165 (pVEGF) reduces ovine AMI size. We hypothesized that combining pVEGF with antiapoptotic erythropoietin (EPO), would limit R-AMI size and protect function and perfusion more than either drug alone. Sheep with 90 min coronary occlusion + reperfusion received empty plasmid (placebo) 3.8 mg, pVEGF 3.8 mg, EPO 1000 UI/kg i.v., or pVEGF+EPO (n=8 each). Fifteen days later, AMI size was smaller with pVEGF (16±5%) and EPO (13±4%) than with placebo (25±7%, p<0.001, ANOVA + Newman-Keuls,), but reduction was maximal with EPO + pVEGF (8±1%, p<0.05 vs. placebo,  EPO and pVEGF). Shortening fraction (echo) was higher (p<0.05) in pVEGF (43.4±5%) and pVEGF+EPO (42.6±4.7%) than EPO (36±7%) and placebo (33.6±6%). Perfusion (SPECT-mibi) worsened only in the placebo group (ischemic burden at baseline: 19±7 LV segments; at 15 days: 22±3, p<0.003, paired t-test). Additional sheep studied 8 hs after R showed lower apoptosis (TUNEL) with EPO (2±2 cel/mm2 vs. 15±10, p<0.04, unpaired t-test). Conclusion: combined EPO and pVEGF in ovine R-AMI is more cardioprotective than either drug alone.