The effect of mannitol versus dimethyl thiourea at attenuating ischemia/reperfusion-induced injury to skeletal muscle

Objective: Mannitol is used as a treatment for skeletal muscle ischemia/rep erfusion (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 eff icacy of mannitol in attenuating I/R injury at the microcirculatory level. Methods: The study was designed as an experimental study with male Wistar r ats. The main outcome measures were intravital microscopy, which was used t o measure capillary perfusion, capillary and venular red blood cell velocit y (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 dy es bisbenzimide and ethidium bromide. Dimethyl thiourea (DMTU), a highly ef fective therapeutic agent of experimental I/R injury, was used as a positiv e control. Results: No-flow ischemia (2 hour) resulted in a 40% drop in capillary perf usion, a decline in capillary and venular VRBC, and increased leukocyte ven ular adherence and tissue infiltration. Tissue injury increased to a consta nt level during reperfusion. Mannitol attenuated capillary malperfusion dur ing the first 60 minutes of reperfusion and prevented a decline in capillar y VRBC. However, mannitol did not reduce tissue injury or leukocyte adheren ce and infiltration during reperfusion. By comparison, DMTU not only preven ted the perfusion deficits and the increases in leukocyte venular adherence and tissue infiltration but significantly reduced the magnitude of tissue injury. Conclusion: Our findings suggest that mannitol may be of limited value for the prevention of early reperfusion-induced injury after no-flow ischemia i n skeletal muscle. By comparison, DMTU was highly efficacious by not only r educing microvascular perfusion deficits but by also reducing leukocyte-end othelial cell interactions and the incidence of cellular injury.