Injection of adeno-associated viral vector encoding vascular endothelial growth factor gene in infarcted swine myocardium: MR measurements of left ventricular function and strain.
OBJECTIVE
To prospectively investigate the long-term effect of adeno-associated viral (AAV) vector-encoding vascular endothelial growth factor gene (VEGF) (AAV-VEGF) on left ventricular (LV) mass and volumes, as well as on regional contractility and circumferential strain, in a swine model of reperfused myocardial infarction.


METHODS
All experimental procedures received approval from the institutional committee on animal research. Of 16 pigs subjected to reperfused myocardial infarction, six were treated, six were controls, and four died during the ischemic intervention. In six animals, cardiac-specific AAV-VEGF was injected into the periinfarcted and infarcted myocardium 1 hour after reperfusion. Magnetic resonance (MR) imaging was performed at 3 days and 8 weeks after infarction by using cine, tagged, and delayed enhancement (with gadoterate meglumine) sequences to measure global and regional LV function and infarct size. At postmortem examination, tissue samples stained with isolectin B4, Masson trichrome, and hematoxylin-eosin were used to characterize injured myocardium. Two-tailed Student t test was used for statistical analysis.


RESULTS
Six treated animals showed no change in mean LV ejection fraction after 8 weeks (40.3%+/-0.9 [standard error of the mean] vs 41.0%+/-0.7) in contrast to a decrease measured in six control animals (41.4%+/-0.7 vs 36.1%+/-0.6, P<.001). AAV-VEGF improved wall thickening and circumferential strain in periinfarcted and remote myocardium. A greater reduction in gadoterate meglumine-enhanced infarct area was measured in treated animals (18.6%+/-1.5 of the LV mass at 3 days vs 9.8%+/-1.0 of the LV mass at 8 weeks, P<.001) compared with control animals (17.7%+/-2.0 vs 14.8%+/-1.0, P=.008). Findings at histopathologic evaluation indicated an increase in vascular density and a decrease in myocyte diameter in the periinfarcted myocardium of treated, compared with control, animals.


CONCLUSIONS
Angiogenesis and arteriogenesis induced by VEGF genes improved regional myocardial strain and wall thickening and preserved ejection fraction after infarction.
Jacquier
Alexis
A
Department of Radiology, University of California San Francisco, 513 Parnassus Ave, HSW 207 B, San Francisco, CA 94134-0628, USA.
Higgins
Charles B
CB
Martin
Alastair J
AJ
Do
Loi
L
Saloner
David
D
Saeed
Maythem
M
D000818:Animals; D003287:Contrast Media; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors; D008279:Magnetic Resonance Imaging; D008536:Meglumine; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D009929:Organ Size; D009942:Organometallic Compounds; D011446:Prospective Studies; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000502:physiology*
D003287:Contrast Media; D009942:Organometallic Compounds; D042461:Vascular Endothelial Growth Factor A; D008536:Meglumine; C072417:gadoterate meglumine