Microvascular Research 55, 175–178 (1998) Article No. MR972066 BRIEF COMMUNICATION Comparison of VEGF Delivery Techniques on Collateral-Dependent Microvascular Reactivity 1 Frank W. Sellke,* ,2 Motohisa Tofukuji,* Roger J. Laham,² Jianyi Li,* Mukesh D. Hariawala,* Stuart Bunting,‡ and Michael Simons² * Department of Surgery and † Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; and ‡ Genentech, Inc., South San Francisco, California Received September 5, 1997 Key Words: angiogenesis; endothelium; heart surgery; genic properties (Miller et al., 1994; Bauters et al., 1994). In addition, VEGF may modify altered coronary micro- growth factor; microcirculation; b-adrenoceptor. vascular regulation in the collateral-dependent myocar- dium (Harada et al., 1996; Sellke et al., 1995). The purpose INTRODUCTION of the present study was to determine the modulating influences of several methods of VEGF delivery on coro- nary blood flow and microvascular reactivity, two deter- Chronic coronary artery occlusion is associated with minants of the development of unstable angina. reduced blood flow to the myocardium subtended by the occluded artery. In addition, the microcirculation in this collateral-dependent myocardium has distinct vasomotor characteristics such as reduced endothelium-dependent MATERIALS AND METHODS relaxation (Harada et al., 1996; Sellke et al., 1996), enhanced contraction to vasopressin (Rapps et al., 1997), and de- creased b-adrenergic-mediated relaxation (Sellke et al., Yorkshire pigs of either sex (25 kg) were anesthetized 1995). This may impact on the development of unstable with intramuscular ketamine (10 mg/kg) and inhala- angina and other vasomotor syndromes. VEGF is a hepa- tion of halothane. Through a thoracotomy, the pericar- rin-binding protein known to have angiogenic and mito- dium was opened and an ameroid occluder was placed around the proximal LCx coronary artery. The pericar- 1 Supported by Grants HL46716 (F.W.S.) and HL53793 (M.S.) from dium was closed and Cefazolin (1 g) was administered the National Heart, Lung, and Blood Institute and a grant from by im injection. Pigs were allowed to recover. Genentech, Inc. Three weeks after placement of the ameroid occluder, 2 To whom correspondence should be addressed at Division of anesthesia was administered and selective coronary an- Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, East giography confirmed LCx artery occlusion in all cases. Campus, Dana 905, 330 Brookline Avenue, Boston, MA 02215. Fax: (617) 667-4898. E-mail: fsellke@bidmc.harvard.edu. Colored microspheres were injected into the left atrium. 0026-2862/98 $25.00 Copyright  1998 by Academic Press All rights of reproduction in any form reserved. 175