The influence of pentoxifylline and torbafylline on muscle blood flow in animals with peripheral arterial insufficiency.

The potential of pentoxifylline to enhance blood flow to relatively ischemic muscle during running was evaluated in rats with peripheral arterial insufficiency. Femoral artery stenosis, sufficient to limit exercise hyperemia but not affect resting blood flow, was surgically induced in adult male rats (approximately 350 g). Day three after stenosis, rats were assigned to either a control (N = 14) or treatment (N = 14) group and exercised 5 days a week for 3 weeks. Exercise tolerance of rats fed pentoxifylline (34 +/- 1.3 mg/kg/day) or an analog (torbafylline; 34 +/- 2.3 mg/kg/day) increased more (P less than .001) than control rats in the third week of treatment. This was evidenced by a higher treadmill speed and longer duration of running. Blood flows determined with 85Sr and 141Ce labeled 15 mu spheres at low (20 m/min) and high (30-35 m/min) treadmill speeds were similar for each group and approximately 50% of that found in normal nonstenosed rats. Blood flows to the entire hindlimb, to the proximal and distal hindlimb segments, and to individual muscle fiber sections were not different between control and pentoxifylline groups. Thus, the increase in exercise tolerance could not be attributed to an increase in muscle blood flow. Rather, an enhanced oxygen extraction by the working limb muscles should lead to the increased VO2, required by the faster running speed in the pentoxifylline rats. This suggests that pentoxifylline may act to improve microvascular flow heterogeneity in working muscle. Our findings support clinical evidence that pentoxifylline is effective in managing patients with peripheral arterial insufficiency.