Vascular Endothelial Growth Factor Is Required for Coronary Collateral Growth in the Rat (original) (raw)

Background-The goal of this study was to determine whether the expression of vascular endothelial growth factor (VEGF) is critical for coronary collateral growth. Previous studies have provided an association between coronary collateral growth and VEGF, but none have allowed determination of a causal role. Methods and Results-We measured coronary collateral growth in rats subjected to repetitive episodes of myocardial ischemia (RI; one 40-second occlusion every 20 minutes for 2 hours 40 minutes, followed by 5 hours 20 minutes of rest, with this 8-hour cycle repeated 3 times per day for 10 days). Collateral growth was measured from blood flow (radioactive microspheres), visualization of arterial-arterial anastomoses (x-ray micro-CT), and maintenance of function during complete coronary occlusion in 3 groups of animals: sham (received instrumentation but no RI), experimental (subjected to RI), and anti-vascular endothelial growth factor (RIϩanti-VEGF 0.6 mg/100 g per day) to block the endogenous actions of VEGF. In the 3 groups, native collateral flow (measurement for RI or sham protocol) averaged 0.2 to 0.3 mL ⅐ min Ϫ1 ⅐ g Ϫ1 of tissue. In the sham group, collateral flow did not increase during the protocol. Collateral flow in the control RI group increased by Ϸ6-fold to 1.63 mL ⅐ min Ϫ1 ⅐ g Ϫ1 tissue, but in the anti-VEGF group, collateral flow did not increase after the RI protocol (0.22 mL ⅐ min Ϫ1 ⅐ g Ϫ1 ).