BETA-ADRENERGIC MODULATION OF THE COLLATERAL-DEPENDENT CORONARY MICROCIRCULATION

The effect of chronic, collateral-dependent perfusion on beta-adrenerg ic coronary microvascular responses was examined. Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 16 pigs. In 8 pigs, heparinized saline containg vascular endothelial g rowth factor (VEGF) was administered into the perivascular space of th e proximal LCx artery using an implanted osmotic pump. After 5-7 weeks , coronary arterial microvessels (70-150 mu m) were studied in a press urized (40 mm Hg) no-flow state with videomicroscopy. beta-Adrenocepto r-mediated relaxations of isolated microvessels from the collateral-de pendent LCx region to isoproterenol (P < 0.01) were markedly reduced, as were those to the adenylate cyclase activator forskolin (P < 0.01), compared to the respective response of vessels from the normally perf used left anterior descending artery region. Responses to the Gs-prote in activator NaF showed a similar trend, but the differences were not significant. Chronic treatment with VEGF normalized responses to isopr oterenol, NaF, and forskolin in the collateral-dependent LCx region. B lood flow in the LCx region increased in both control (P < 0.01) and V EGF-treated (P < 0.05) groups during rapid atrial pacing. The absolute increase in LCx blood flow was greater in the VEGF group than in the control group at rest (P < 0.05), but not during rapid pacing. Thus, b eta-adrenergic microvascular relaxation is impaired in the collateral- dependent coronary microcirculation. The periadventitial delivery of V EGF improves myocardial perfusion to the collateral-dependent area and preserves beta-adrenergic-mediated relaxation of microvessels in the collateral-dependent myocardium. (C) 1995 Academic Press, Inc.