Vascular endothelial growth factor administration in chronic myocardial ischemia.
Vascular endothelial growth factor (VEGF) is a potent mitogen capable of stimulating angiogenesis. We examined the effect of VEGF administration in a model of chronic porcine myocardial ischemia. Nineteen pigs were instrumented with proximal left circumflex coronary artery (LCX) Ameroid constrictors. In eight animals VEGF (2 microgram) with heparin (50 U) was administered extraluminally to the LCX myocardium with an osmotic pump for 4 wk and 11 other animals served as controls. VEGF-treated animals demonstrated higher flow in the LCX territory during both rest and pacing compared with untreated controls (rest: 1.35 +/- 0.1 vs. 0.80 +/- 0.09 ml.min-1.g-1; pacing; 2.01 +/- 0.37 vs. 1.01 +/- 0.07 ml.min-1.g-1, P < 0.05, VEGF vs. controls). The observed improvement in regional coronary flow in VEGF-treated animals resulted in better preservation of endothelium-dependent microvessel relaxation as well as fractional LV shortening in the LCX territory during pacing in the VEGF-treated than in control animals (controls: 7.1 +/ 2.6 vs. 3.6 +/- 2.0%, rest vs. pacing; VEGF: 6.9 +/- 2.9 vs. 6.3 +/- 2.9%, rest vs. pacing). We conclude that VEGF administration in a gradual coronary occlusion model in pigs results in improvement of coronary flow and preservation of regional hemodynamics in the compromised myocardium.
Harada
K
K
Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Department of Medicine (Cardiovascular Division Harvard Medical School, Boston Massachusetts USA.
Friedman
M
M
Lopez
J J
JJ
Wang
S Y
SY
Li
J
J
Prasad
P V
PV
Pearlman
J D
JD
Edelman
E R
ER
Sellke
F W
FW
Simons
M
M
D000818:Animals; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors