EXERCISE TRAINING ENHANCES BASIC FIBROBLAST GROWTH FACTOR-INDUCED COLLATERAL BLOOD-FLOW

This study evaluated whether daily exercise would enhance the peripher al collateral vessel development found in response to exogenous basic fibroblast growth factor (bFGF) infusion. After bilateral femoral occl usion, male Sprague-Dawley rats (similar to 325 g) received intra-arte rial infusions of either bFGF (1 mu g/day; n = 15) or carrier solution (n = 13) via osmotic pumps for 2 wk. Subgroups of each treatment were kept sedentary (cage activity) or trained by walking at 20 m/min at 1 5% grade, two times a day, 5 days/wk for 4 wk. Training markedly incre ased citrate synthase activity in the active muscle (P < 0.001). Muscl e function and blood flows (Sr-85 microsphere) were evaluated using an isolated hindquarter perfused at 100 mmHg via the abdominal aorta. Th e significant increase in blood flow to the entire hindlimb in the sed entary animals, caused by bFGF infusion (P < 0.05), was further increa sed (P < 0.01) in the bFGF-trained group. The quantitatively largest i ncreases in blood flows were observed in the collateral-dependent tiss ues of the distal hindlimb. Blood flows to the entire calf muscle grou p increased similar to 140% in carrier-trained (P < 0.001), similar to 180% in bFGF sedentary (P < 0.001), and similar to 240% in the bFGF-t rained (P < 0.001) groups compared with the carrier sedentary group. T he increases in collateral blood flow were functionally important, as improvements in calf muscle performance correlated with measured blood flows. Our results demonstrate that exogenous bFGF administration in combination with a moderate-intensity exercise program greatly increas es collateral-dependent blood flow and improves muscle performance. Th at physical activity enriched the bFGF response is consistent with the hypothesis that hemodynamic factors are important contributors to col lateral vessel enlargement.