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Efficacy of Intracoronary Administration of Ad5IGF‐1 and Ad5FGF‐2 to Treat Acute Myocardial Infarction in a Porcine Model of Coronary Artery Occlusion and Reperfusion
Author(s) -
Shi Weiwei,
Schmarkey Laura Susan,
Jiang Rong,
Bone C. Collin,
Katzmark Sara,
Engler Robert L,
Rubanyi Gabor M,
Vinten-Johansen Jakob
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1134.3
Subject(s) - medicine , transfection , cardiology , myocardial infarction , ejection fraction , coronary occlusion , angioplasty , infarction , artery , saline , heart failure , biology , genetics , cell culture
We tested the hypothesis that intracoronary delivery of an adenoviral vector (Ad5) encoding transgenes for either Insulin‐like growth factor‐I (IGF‐1) or fibroblast growth factor 2 (FGF‐2) would reduce myocardial I/R injury in a closed‐chest porcine model. In Yorkshire pigs the LAD was occluded by a fluoroscopically guided angioplasty balloon for 75 min, and assigned to 4 groups based on an intracoronary infusion of 1) saline, 2) IGF‐1, 3) FGF‐2 or 4) Ad5 encoding luciferase (Ad5Luc to quantify transfection) at 15 min of reperfusion to the LAD and to LCx. Reperfusion was carried out for 3 or 14 days. There were no hemodynamic or rhythm disturbances associated with any infusion. After 3 days of R expression of luciferase was robust in samples from target myocardium, with sequentially less in the border zone and remote LV myocardium, confirming viral transfection. After 14 days of R, the viral transfection decreased significantly. Ejection fraction (EF) recovered toward baseline values in all groups (Figure A) without group differences. There were no group differences in systolic and diastolic performance (pressure‐volume relations) among groups. Infarct size [% of LV or area at risk mass] was similar among the four groups (Figure B). In conclusion, Ad5 transfection with IGF‐1 or FGF‐2 was safe, but did not have overall treatment effect on LV performance indices or infarct size 14 days after I/R despite viral transfection.