Significant, but limited collateral blood flow increases occur with prolonged training in rats with femoral artery occlusion.

This study examined the capacity of collateral dependent blood flow induced by a prolonged treadmill training program, as compared to a low collateral resistance model created by femoral artery to vein (A-V) shunt. Sprague-Dawley rats, with bilateral femoral artery occlusion were confined to cage activity (Sed, n=9) or trained by daily treadmill exercise (Tr, n=15; up to ≈350 min/d) for 15 weeks. Another set of animals received a femoral A-V anastomosis in one limb and treated with (n=4) or without VEGF(165) (n=9) infusion for 2 weeks. The contralateral side was used as control. Blood flow (BF) was measured with isotope labeled microspheres. Maximal calf muscle BF increased by 15 week training (up to 100±5.0 ml x min(-1) x 100g(-1) (p<0.05); 0.71±0.04 ml x min(-1) x 100g(-1) x mmHg(-1)), a response better (20-25%) than the less demanding training programs used previously. In contrast, femoral A-V shunt with VEGF(165) increased calf muscle conductance to 1.70±0.3 ml x min(-1) x 100 g(-1) x mmHg(-1) that is similar to blood flows observed in non-occluded rats during maximal running. Our data indicate that the collateral circuit development is related to the driving stimulus and that exercise training, does not provide a maximal stimulus for adaptation that is possible. Nonetheless, exercise training results in profound increases in exercise capacity associated with this enhanced collateral blood flow. Our results illustrate that vascular adaptations can be much greater when physiologically induced stimuli are enhanced at the time of therapeutic angiogenesis.