@article {Hariawala:June 1996:0022-4804:77,
	author = "Hariawala M.D.",
	author = "Horowitz J.R.",
	author = "Esakof D.",
	author = "Sheriff D.D.",
	author = "Walter D.H.",
	author = "Keyt B.",
	author = "Isner J.M.",
	author = "Symes J.F.",
	title = "VEGF Improves Myocardial Blood Flow but Produces EDRF-Mediated Hypotension in Porcine Hearts",
	journal = "Journal of Surgical Research",
	volume = "63",
	year = "June 1996",
	abstract = "<P> Several recent studies have demonstrated the potential for improving myocardial perfusion by the continuous administration of angiogenic growth factors. Studies in our laboratory have shown that a single intraarterial or intravenous bolus of the endothelial cell specific mitogen vascular endothelial growth factor (VEGF) can significantly improve perfusion in a rabbit ischemic limb model. To test the efficacy of this therapeutic approach in chronic myocardial ischemia, 18 Yorkshire pigs underwent a left thoracotomy followed by placement of an ameroid constrictor around the proximal circumflex coronary artery. Gradual occlusion of the artery (26 ? 4 days) was accompanied by identifiable hypokinesis of the posterolateral wall of the left ventricle (2D echo). Thirty days postoperatively, rhVEGF 165 (2 mg; n = 8) or saline ( n = 10) was administered directly into the left coronary ostium. Postadenosine myocardial perfusion studies using colored microspheres 30 days later demonstrated superior blood flow in the ischemic zone of the VEGF-treated hearts (ischemic/normal ratio 1.09 vs 0.97, P &lt; 0.05) compared with those receiving saline injection. Four of eight VEGF-treated animals succumbed, however, to severe hypotension following VEGF administration. Therefore 500 mug of VEGF were administered intracoronary to five normal pigs. A significant drop in mean arterial pressure (-44.4 ? 3.2%, P &lt; 0.05 vs baseline) and peripheral resistance (-13.2 ? 4.5%, P &lt; 0.05 vs baseline) was accompanied by increased heart rate. IV administration of N omega -nitro- L -arginine (L-NNA), an EDRF inhibitor, restored blood pressure to baseline. We conclude that a single intracoronary bolus of VEGF is capable of significantly augmenting flow to collateral-dependent ischemic myocardium. The associated hypotension appears to be EDRF-mediated. Further studies are needed to define the best dose and route of administration of VEGF for the treatment of coronary insufficiency.</P>",
	pages = "77-82(6)",
	url = "http://www.ingentaconnect.com/content/ap/jr/1996/00000063/00000001/art00226"
}