Regional capillary perfusion in muscles with limited blood supply: effects of torbafylline.

Abstract

Severe limitation of blood supply mainly affects the oxidative regions of skeletal muscles. In mammals, they are located medially and are thus not accessible to direct observation. We therefore investigated capillary perfusion in rat tibialis anterior, which has a predominantly glycolytic cortex and oxidative core, using timed intraarterial injection of the fluorochrome thioflavine S conjugated with serum albumin. Muscles with intact blood supply were compared with those in which the blood supply had been limited for 5 weeks by unilateral ligation of the common iliac artery. The effect of a new xanthine derivative, torbafylline (1% solution, 12.5 mg/kg, in two daily doses by gavage, 7 days/week), was also studied. The capillary/fibre ratio was estimated for perfused capillaries (those filled with fluorochrome within 7.5 s after injection; Cp) and all capillaries (those subsequently stained for alkaline phosphatase; Ct), from micrographs of cryostat sections. Regional differentiation in relative capillary perfusion was evident in all muscles samples. Cp:Ct was 0.406 +/- 0.086 (mean +/- 95% CI) in the glycolytic cortex of the contralateral normal muscle, and 0.255 +/- 0.071 in the oxidative core. Muscles with limited blood supply had a significantly lower proportion of perfused capillaries, 0.119 +/- 0.056 in glycolytic and 0.034 +/- 0.038 in oxidative regions. Torbafylline treatment nearly doubled perfusion in the glycolytic regions (Cp:Ct = 0.216 +/- 0.137) and nearly quadrupled it in oxidative (Cp:Ct = 0.121 +/- 0.151) regions of ischaemic muscles. It also improved perfusion in the contralateral muscles (Cp:Ct = 0.705 +/- 0.085 in the glycolytic cortex and 0.583 +/- 0.230 in the oxidative core).(ABSTRACT TRUNCATED AT 250 WORDS)