HEPARIN INCREASES EXERCISE-INDUCED COLLATERAL BLOOD-FLOW IN RATS WITHFEMORAL-ARTERY LIGATION

The potential for heparin to enhance the training-induced increase in collateral-dependent blood flow to the distal hind-limb muscles was ev aluated after bilateral femoral artery ligation in adult male rats (ap proximate to 350 g). Rats received either saline (n=34) or heparin (n= 36) injections and were kept sedentary (limited to cage activity) or e xercised 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 a pproximate to 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 sal ine-treated rats, exer cised by the moderate-speed protocol, were run for the same time each day. Collateral-dependent blood flow to the dis tal limb tissue was determined by using 15-mu m Sr-85-labeled microsph eres in an isolated hindquarter preparation perfused in the descending aorta at 100 mm Hg. For comparison with the above groups, sedentary a nimals with acute femoral artery ligation and without femoral obstruct ion were included. Exercise tolerance increased from approximate to 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, w as further increased by heparin administration (P<.001), and generally scaled with recovery of blood flow. Collateral-dependent blood flow i n 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 exercis ed 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 alt er collateral-dependent blood flow in the absence of exercise training . Thus, exercise appears to impart an essential stimulus for collatera l vessel development that is enhanced by heparin administration.