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Oxygenated perfluorocarbon emulsion has been shown to preserve feline cerebral function after ischemia. The postulated protective effects of perfluorocarbons include improvement of blood rheology and prevention of neutrophil adherence by nonchemical inhibition of surface receptors. In this study, we used a well-described gracilis muscle model to investigate whether oxygenated perfluorocarbon can minimize skeletal muscle necrosis by mitigating the degree of leukosequestration. In eight adult mongred dogs, both gracilis muscles were weighted and then subjected to 6 hours of normothermic ischemia followed by 48 hours of normothermic reperfusion. However, one randomly selected side (experimental side) was infused with oxygen (O2) Fluosol-DA 20% (4.4±0.2 mL O2/100 mL) intra-arterially at 12 mL/min for 40 minutes immediately after ischemia. Muscle biopsy specimens were obtained before ischemia and after 1 hour and 48 hours of reperfusion to estimate myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. After 48 hours, both gracilis muscles were harvested and weighted in all animals. Muscle necrosis was measured by serial transections, nitroblue tetrazolium staining, and computerized planimetry. The transmuscular oxygen tension (pO2) of the gracilis muscle on the experimental side increased from 2 to 4 mm Hg during ischemia to 315±50 mm Hg during O2 Fluosol-DA 20% infusion. The percentage of muscle necrosis on the control side was 48.08%±8.46%, compared with 27.62%±6.96% on the experimental side (p <0.001). MPO activity was significantly higher at 48 hours of reperfusion compared with pre-ischemic and 1-hour reperfusion values (5.46±1.52 U/mg tissue protein versus 0.06±0.01 U/mg tissue protein and 0.16±0.06 U/mg tissue protein, respectively, in the control group; 1.78±0.60 U/mg tissue protein versus 0.16±0.08 U/mg tissue protein and 0.27±0.10 U/mg tissue protein, respectively, in the experimental group, p<0.05). However, MPO activity at 48 hours of reperfusion in the experimental group was significantly lower than in the control group (p<0.05). There was no difference in the percentage of weight gain between the control and the experimental groups (38.31%± 9.36% and 28.34%±7.35%, respectively, p >0.05). These data show that perfluorocarbons minimize the extent of skeletal muscle necrosis in this canine model. Based on our data on MPO activity, we believe that the protective effect of perfluorocarbons is in part due to the decreased leukosequestration in the muscle during the periods of ischemia and reperfusion. The potential for clinical application of this new treatment modality is very attractive, since high mortality and morbidity rates continue to be reported in patients with acute limb ischemia.
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*This work has been designated the 1992 Peter B. Samuels PrizeEssay by a resident. Dr. Mohan is the recipient of the award.
**Presented at the 20th Annual Meeting of the Society for ClinicalVascular Surgery, Orlando, Florida, March 25–29, 1992.
© 1992 Reed Publishing USA. Published by Elsevier Inc.