Transmyocardial revascularization and vascular endothelial growth factor administration enhance effect of cell transplantation for myocardial infarct repair in rats.
OBJECTIVE
To test the hypothesis that transmyocardial revascularization and vascular endothelial growth factor (VEGF) administration would enhance cell transplantation effect for myocardial infarct.


METHODS
After ligation of left anterior descending coronary artery, the recipient rats were treated with transmyocardial revascularization. Ten minutes after transmyocardial revascularization, recombinant murine VEGF165 was injected into the clot of the drilling channel and the myocardium bordering the channel. Two weeks after transmyocardial revascularization, differentiated cells from embryo stem cells were injected into the infarcted myocardium and vascular endothelial growth factor was injected again in the same dose. Four weeks after the differentiated cells were grafted, cardiac function was assessed by hemodynamic measurements. Capillary density and infarct size in the infarct region were measured with a previous experimental method. Graft histology and morphology were also evaluated.


RESULTS
Four weeks after the differentiated cells were grafted, myocardial infarct rats treated with transmyocardial revascularization and vascular endothelial growth factor showed a significantly higher cardiac function in hemodynamic measurements (P<0.01) than other control groups. A significant increase in capillary density and reduction in infarct size were observed in the infarct hearts of the myocardial infarct rats under combination therapy (P<0.01).


CONCLUSIONS
Before differentiated cell transplantation, transmyocardial revascularization and vascular endothelial growth factor administration caused an angiogenesis effect to enhance neovascularization. It may be superior in attenuating the progression of cardiac dysfunction in the rat model compared with the myocardial infarct rat transplanted cell alone.
Wang
Yanmei
Y
Department of Anatomy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Dong
Yilong
Y
Li
Ruofan
R
Wang
Dong
D
Tang
Hongmei
H
Liu
Wei
W
Zhang
Xiaodong
X
D000704:Analysis of Variance; D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002470:Cell Survival; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005854:Germ Cells / Q000637:transplantation; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009204:Myocardial Revascularization; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A