Effect of torbafylline on muscle blood flow, performance, and capillary supply in ischemic muscles subjected to varying levels of activity

Abstract

Torbafylline, a novel xanthine derivative, was given to rats by gavage (2 × 25 mg∙kg−1∙day−1, morning and evening) to study its effect upon fast muscles (tibialis anterior and extensor digitorum longus) made ischemic by unilateral ligation of the common iliac artery and subjected to two types of activity imposed by chronic electrical stimulation at 10 Hz: (i) strenuous, 6 h∙day−1 as 3 × 2 h with 90- to 120-min intervals or (ii) mild, 105 min∙day−1 as 7 × 10–15 min with 90- or 85-min intervals for 12–14 days. Some of the deleterious effects on ischemic muscles of strenuous activity (reduced blood flow during contractions, less resistance to fatigue) were remedied by torbafylline treatment, and values normalized. Most notably, torbafylline significantly reduced the degree of capillary endothelial cell swelling. In addition, the degree of atrophy was reduced and fatigue resistance improved in muscles contralateral to ischemic, which had been impaired with the strenuous regime. Torbafylline treatment had little further effect on ischemic muscles subjected to mild stimulation, which on its own improved functional hyperemia, resistance to fatigue, and the capillaries per fibre ratio in tibialis anterior, although it did significantly increase the capillary per fibre ratio in extensor digitorum longus. These data indicate a possible role for torbafylline as an adjunct to exercise therapy for chronic muscle ischemia.Key words: ischemia, muscle stimulation, methylxanthine, blood flow, fatiguability, capillarity.