Heparin Increases Exercise-Induced Collateral Blood Flow in Rats With Femoral Artery Ligation

Abstract

The potential for heparin to enhance the training-induced increase in collateral-dependent blood flow to the distal hind-limb muscles was evaluated after bilateral femoral artery ligation in adult male rats (≈350 g). Rats received either saline (n=34) or heparin (n=36) injections and were kept sedentary (limited to cage activity) or exercised on a treadmill 5 days per week up a 15% incline by one of two protocols: (1) exercise at a constant moderate speed (20 m/min) for ≈6 wks or (2) exercise at a progressively increased speed for 7 to 8 weeks (started at 20 m/min, increased at 15 minutes to 25 m/min, and then increased at 30 minutes to 30 m/min). Heparin- and saline-treated rats, exercised by the moderate-speed protocol, were run for the same time each day. Collateral-dependent blood flow to the distal limb tissue was determined by using 15-μm ⁸⁵Sr-labeled microspheres in an isolated hindquarter preparation perfused in the descending aorta at 100 mm Hg. For comparison with the above groups, sedentary animals with acute femoral artery ligation and without femoral obstruction were included. Exercise tolerance increased from ≈7 minutes initially to 30 to 40 minutes per bout; tolerance was greater in the heparin-injected rats than in the saline-injected rats (P<.05). Muscle performance of the gastrocnemius-plantaris-soleus muscle group (GPS) during isometric contractions in situ improved with training, was further increased by heparin administration (P<.001), and generally scaled with recovery of blood flow. Collateral-dependent blood flow in the GPS of the heparin-injected exercised groups (40±4 and 56±3 mL/min per 100 g) was greater than that in the saline-injected exercised groups (19±3 and 30±5 mL/min per 100 g), and blood flow in both of these groups was greater than that in the sedentary groups (14±4 and 12±2 mL/min per 100 g) (P<.005). Heparin injections did not alter collateral-dependent blood flow in the absence of exercise training. Thus, exercise appears to impart an essential stimulus for collateral vessel development that is enhanced by heparin administration.