IngentaConnect VEGF Improves Myocardial Blood Flow but Produces EDRF-Mediated Hy...

Authors: Hariawala M.D.^{1, 2}; Horowitz J.R.^{1, 2}; Esakof D.^{1, 2}; Sheriff D.D.^{1, 2}; Walter D.H.^{1, 2}; Keyt B.^{1, 2}; Isner J.M.^{1, 2}; Symes J.F.^{1, 2}

Source: Journal of Surgical Research, Volume 63, Number 1, June 1996 , pp. 77-82(6)

Publisher: Academic Press

Abstract:

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 < 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 < 0.05 vs baseline) and peripheral resistance (-13.2 ? 4.5%, P < 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.

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VEGF Improves Myocardial Blood Flow but Produces EDRF-Mediated Hypotension in Porcine Hearts