Egginton S, Hudlicka O, Glover M
Department of Physiology, University of Birmingham Medical School, UK.
Int J Microcirc Clin Exp. 1993 Feb;12(1):33-44.
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.
研究了单侧结扎髂总动脉（L）的大鼠缺血及对侧趾长伸肌（EDL）、膈肌和左心室乳头肌的毛细血管超微结构，还研究了缺血刺激肌肉（SL）以及用新型黄嘌呤衍生物托巴茶碱治疗的动物的缺血刺激肌肉（SL&T）的毛细血管超微结构。通过植入电极以10Hz频率每天刺激肌肉7次，持续2周。早晚经口灌胃给予托巴茶碱或水。对毛细血管超微结构的名义评估显示，缺血肌肉中52.7±8.7%（平均值±标准误）的毛细血管存在内皮肿胀，对侧肌肉中为35.2±5.6%，膈肌和乳头肌中约为30%。对缺血肌肉进行刺激后，缺血及对侧EDL、膈肌和乳头肌中这一比例分别增加至62.6±6.2%（与L组相比无显著差异）、57.8±9.5%（与L组相比p<0.05）、62.6±6.3（与L组相比p<0.05）和43.7±4.2%（与L组相比p<0.05）。给予托巴茶碱后，缺血肌肉中肿胀毛细血管的比例降至37.8±6.1%、45%（与SL组相比p<0.02），乳头肌中降至26.2±2.1%（p<0.001），对侧EDL和膈肌中的作用较小。体视学分析表明，与对侧肌肉相比，刺激导致毛细血管大小显著增加。所有组的管腔体积密度相似（Vv=0.36 - 0.39），而对照组Vv=0.47，这反映了EDL毛细血管群内的结构异质性。对于大多数成分而言，这种动物体内的差异掩盖了药物治疗效果，例外的是Vv（细胞核），在SL&T组中最小。因此，缺血肌肉中的活动可导致肌肉中广泛的毛细血管内皮损伤，而托巴茶碱减轻这种肿胀可能解释了该药物对毛细血管灌注和功能的有益作用。
