Fine structure of capillaries in ischaemic and non ischaemic rat striated muscle. Effect of torbafylline.

Capillary ultrastructure was studied in ischaemic and contralateral extensor digitorum longus (EDL) muscle, in the diaphragm and left ventricular papillary muscle of rats with unilateral ligation of the common iliac artery (L), in ischaemic stimulated muscles (SL), and in ischaemic stimulated muscles of animals treated with a new xanthine derivative, torbafylline (SL&T). Muscles were stimulated at 10Hz via implanted electrodes 7 times/day for 2 weeks. Torbafylline or water was given by gavage morning and evening. Nominal evaluation of capillary ultrastructure revealed endothelial swelling in 52.7 +/- 8.7% (mean +/- SEM) capillaries in ischaemic muscles, 35.2 +/- 5.6% in contralateral muscles and about 30% in the diaphragm and papillary muscle. Stimulation of ischaemic muscles increased this proportion to 62.6 +/- 6.2% (not significant vs. L), 57.8 +/- 9.5% (p < 0.05 vs. L), 62.6 +/- 6.3 (p < 0.05 vs. L) and 43.7 +/- 4.2% (p < 0.05 vs. L) in ischaemic and contralateral EDL, diaphragm and papillary muscle, respectively. Administration of torbafylline reduced the proportion of swollen capillaries to 37.8 +/- 6.1.45% (p < 0.02 vs. SL) in ischaemic muscles, and to 26.2 +/- 2.1% (p < 0.001) in papillary muscle, with a smaller effect in the contralateral EDL and the diaphragm. Stereological analysis showed that stimulation led to a marked increase in capillary size vs. contralateral muscles. A similar lumen volume density across all groups (Vv = 0.36-0.39), vs. control Vv = 0.47, reflected structural heterogeneity within the capillary population of EDL. For most components this intra- animal variation obscured drug treatment effects, the exception being Vv(nucleus) which was least in SL&T. Activity in ischaemic muscles can thus result in widespread capillary endothelial damage in muscles, and attenuation of this swelling by torbafylline may explain the beneficial effect of this drug on capillary perfusion and performance.