Schlag M G, Clarke S, Carson M W, Harris K A, Potter R F
London Health Sciences Centre Research, Inc, and the Departments of Surgery and Medical Biophysics, University of Western Ontario, Canada.
J Vasc Surg. 1999 Mar;29(3):511-21. doi: 10.1016/s0741-5214(99)70280-6.
Mannitol is used as a treatment for skeletal muscle ischemia/reperfusion (I/R) injury in humans, despite the fact that its effectiveness in vivo is still disputed. The purpose of this study was to determine the efficacy of mannitol in attenuating I/R injury at the microcirculatory level.
The study was designed as an experimental study with male Wistar rats. The main outcome measures were intravital microscopy, which was used to measure capillary perfusion, capillary and venular red blood cell velocity (VRBC), and leukocyte-endothelial interactions in the extensor digitorum longus muscle of the rat hind limb before and after ischemia. In addition, tissue injury was assessed during reperfusion with the fluorescent vital dyes bisbenzimide and ethidium bromide. Dimethyl thiourea (DMTU), a highly effective therapeutic agent of experimental I/R injury, was used as a positive control.
No-flow ischemia (2 hour) resulted in a 40% drop in capillary perfusion, a decline in capillary and venular VRBC, and increased leukocyte venular adherence and tissue infiltration. Tissue injury increased to a constant level during reperfusion. Mannitol attenuated capillary malperfusion during the first 60 minutes of reperfusion and prevented a decline in capillary VRBC. However, mannitol did not reduce tissue injury or leukocyte adherence and infiltration during reperfusion. By comparison, DMTU not only prevented the perfusion deficits and the increases in leukocyte venular adherence and tissue infiltration but significantly reduced the magnitude of tissue injury.
Our findings suggest that mannitol may be of limited value for the prevention of early reperfusion-induced injury after no-flow ischemia in skeletal muscle. By comparison, DMTU was highly efficacious by not only reducing microvascular perfusion deficits but by also reducing leukocyte-endothelial cell interactions and the incidence of cellular injury.
尽管甘露醇在体内的有效性仍存在争议，但它被用于治疗人类骨骼肌缺血/再灌注（I/R）损伤。本研究的目的是确定甘露醇在减轻微循环水平的I/R损伤方面的疗效。
本研究设计为以雄性Wistar大鼠为对象的实验研究。主要观察指标是活体显微镜检查，用于测量大鼠后肢趾长伸肌在缺血前后的毛细血管灌注、毛细血管和小静脉红细胞速度（VRBC）以及白细胞与内皮细胞的相互作用。此外，在再灌注期间用荧光活性染料双苯甲酰亚胺和溴化乙锭评估组织损伤。二甲基硫脲（DMTU）是一种治疗实验性I/R损伤的高效药物，用作阳性对照。
无血流缺血（2小时）导致毛细血管灌注下降40%，毛细血管和小静脉VRBC下降，白细胞小静脉黏附及组织浸润增加。再灌注期间组织损伤增加至恒定水平。甘露醇减轻了再灌注最初60分钟内的毛细血管灌注不良，并防止了毛细血管VRBC下降。然而，甘露醇在再灌注期间并未减轻组织损伤或白细胞黏附及浸润。相比之下，DMTU不仅防止了灌注不足以及白细胞小静脉黏附和组织浸润的增加，而且显著降低了组织损伤的程度。
我们的研究结果表明，甘露醇在预防骨骼肌无血流缺血后早期再灌注诱导的损伤方面可能价值有限。相比之下，DMTU非常有效，不仅减少了微血管灌注不足，还减少了白细胞与内皮细胞的相互作用以及细胞损伤的发生率。
