THE EFFECT OF ALPHA(1) ADRENOCEPTOR ANTAGONIST PRAZOSIN ON CAPILLARY SUPPLY, BLOOD-FLOW AND PERFORMANCE IN A RAT MODEL OF CHRONIC MUSCLE ISCHEMIA

Objective: This study explores whether the a, blocker prazosin improve s capillarisation, blocker prazosin and muscle performance in chronica lly ischaemic muscles. Design: Rat skeletal muscles were made ischaemi c by unilateral ligation of the common iliac artery. The animals recei ved prazosin and muscle blood pow, performance and capillary supply we re studied 2 or 5 weeks later. Materials and methods: Prazosin (50 mg/ l) was given in drinking water to animals with limited or intact blood supply. Muscle isometric twitch tension and fatigue index and blood f low at rest and during contractions (estimated by radio labelled micro spheres) were measured in tibialis anterior, TA, and extensor digitoru m longus, EDL. Capillary supply (capillary/fibre ratio, C/F) was estim ated in frozen muscle sections stained for alkaline phosphatase in TA, EDL and soleus, S. Results: Prazosin increased significantly capillar y supply in ischaemic muscles after 2 and 5 weeks and bloodflow during contractions (control muscles 163+/-6 mi. 100g(-1) min(-1); ligated 2 weeks 25+/-7, ligated+prazosin 116+/-38; ligated 5 weeks 27+/-7, +pra zosin 137+/-29, p<0.05 vs. ligated). Fatigue index (final/peak tension over 5 min contractions at 4Hz in %) was significantly improved by pr azosin after 2 weeks (FI=69+/-3% controls, 35+/-4% ligation, 60+/-3% l igation + prazosin) and less after 5 weeks (52+/-12% ligation, 61+/-3% ligation +prazosin). In contrast, prazosin had no effect on muscle pe rformance in normal muscles in spite of if increased C/F and bloodflow . Conclusions: Alpha, adrenoceptor blockade is an effective way for im provement of capillary supply, blood flow and muscle performance in is chaemic muscles; the effect on muscle performance is most pronounced 2 weeks after induction of ischaemia.