Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model.
We previously reported adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF) as a new treatment for leg ischemia. This time, we tested this method on a swine myocardial ischemia model, seeking the possibility of its application for ischemic heart disease. An ameroid constrictor was placed around the proximal left circumflex branch of pigs to induce myocardial ischemia. Simultaneously, a skin section was harvested and fibroblasts were cultured. Fibroblasts were then infected with adenovirus vector containing a bFGF cDNA with a secretory signal sequence (bFGF group, n=8) or a LacZ cDNA (control group, n=8). At 28 days after constrictor implantation, 2.5 x 10(6) fibroblasts were administered into each of the right and left coronary arteries. The injected fibroblasts accumulated in the myocardium without causing myocardial ischemia. Echocardiography, electromechanical mapping and coronary arteriography were conducted just before and 28 days after fibroblast injection, and regional left ventricular myocardial blood flow was measured 28 days after fibroblast injection. These evaluations revealed that the bFGF group exhibited significant development of collateral vessels and improvement of myocardial contraction in the ischemic area compared with the control group. We believe that this method is a promising treatment strategy for ischemic heart disease.
Ninomiya
M
M
Department of Cardiac Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Koyama
H
H
Miyata
T
T
Hamada
H
H
Miyatake
S
S
Shigematsu
H
H
Takamoto
S
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D017690:Cell Transplantation / Q000379:methods; D003097:Collateral Circulation; D017023:Coronary Angiography; D003331:Coronary Vessels; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D014161:Transduction, Genetic / Q000379:methods*
D016222:Fibroblast Growth Factor 2