Percutaneous transendocardial VEGF gene therapy: MRI guided delivery and characterization of 3D myocardial strain.
BACKGROUND
Patients with myocardial infarcts have unfavorable left ventricular (LV) remodeling and devastating outcomes. This study was performed to determine whether VEGF-gene delivered transendocardially under MR-guidance improves LV three-dimensional (3D) strain (circumferential, longitudinal and radial), reduces infarct transmurality and increases vascular density in a canine model of permanent LAD coronary artery occlusion.


METHODS
Imaging was performed using a 1.5-T MR scanner. Three days after occlusion, a percutaneous catheter was advanced under MR-guidance into the LV chamber for transendocardial delivery of VEGF-gene therapy (n=6) or LacZ-gene as control (n=6) into infarcted and peri-infarcted myocardium. MRI was performed before (3 days) and after (50 days) the delivery of therapy using cine, tagged and delayed contrast enhancement. Histochemical and pathological stains were used to assess myocardial viability and vascular density, respectively.


RESULTS
Transendocardial delivery of VEGF-gene therapy and LacZ-gene under MRI guidance was successful in all animals. Significant improvement in 3D strain was observed within 50 days in treated animals. On the other hand, control animals demonstrated deterioration in regional strain over time. Significant reductions in infarct transmurality and increases in capillary and arteriole densities were also observed in VEGF-treated as compared to control animals.


CONCLUSIONS
MR-guided transendocardial delivery of VEGF-gene improved myocardial strain and enhanced transmural infarct resorption. This minimally invasive technique may be useful for delivery of local therapies, designed to promote angiogenesis or myogenesis.
Dicks
Demetrius
D
Department of Radiology and Biomedical Imaging, 513 Parnassus Avenue, HSW207B, University of California, San Francisco, CA, USA.
Saloner
David
D
Martin
Alastair
A
Carlsson
Marcus
M
Saeed
Maythem
M
D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D004285:Dogs; D004699:Endocardium / Q000473:pathology*; D015316:Genetic Therapy / Q000379:methods*; D006571:Heterocyclic Compounds; D021621:Imaging, Three-Dimensional; D019028:Magnetic Resonance Imaging, Cine; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D009942:Organometallic Compounds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D016277:Ventricular Function, Left / Q000502:physiology
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D042461:Vascular Endothelial Growth Factor A; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate