Acute skeletal muscle ischemia and reperfusion in the rat : The role of leukocytes and the effect of hyperbaric oxygen on microcirculation and metabolism during reperfusion

University dissertation from Linköping : Linköpings universitet

Abstract: Much experimental work in recent years seems to indicate that reperfusion after long periods of ischemia can damage tissue. Suggested factors of importance are accumulation of polymorphonuclear leukocytes (PMNs) and production of reactive oxygen metabolites (ROMs). In these experimental studies, a rat hindlimb tourniquet model was used to investi-gate the accumulation and the role of PMN's and the effect of hyperbaric oxygen (HBO) on post-ischemic skeletal muscle dysfunction. HBO was used, because post-ischemic oxygen delivery is said to be associated with production of ROM's. The activity of the PMN-specific enzyme myelo-peroxidase (MPO) in muscle homogenates was used as an index for the presence of PMNs.After 3 hours of ischemia, reperfusion periods longer than 1 hour were required to observe a significantly increased MPO activity com-pared to non-ischemic control. There was a significant increase in MPO activity after 5 hours of reperfusion, which was further increased up to 24 hours of reperfusion and had returned to control levels after 72 hours ofreperfusion. There was no significant correlation between MPO activity, edema and blood flow seen during reperfusion following 3 or 4 hours of ischemia, with one exception. Mter 4 hours of ischemia and I hour of reperfusion there was a significant correlation between the MPO activity and the extent of edema.Prevention of post-ischemic muscle accumulation of PMNs by pretreatment with antineutrophil serum did not affect the microvascular dysfunction (reduced blood flow and edema formation) and the metabolic restitution after 18 hours of reperfusion following 4 hours of ischemia.HBO treatment during the first hour of reperfusion after 3 hours of ischemia significantly increased the levels of ATP, PCr and glutathione and reduced the edema seen after 5 hours reperfusion. After 4 hours of ischemia HBO treatment failed to improve the levels of ATP, PCr and glutathione and affect the edema but improved the blood flow seen after 5 hours of reperfusion.It is concluded from these results that in this model, damage by PMN's seems minor during reperfusion. The improvement seen with HBO indicate that there is a prevailing or lingering effect of residual hypoxia in the post-ischemic muscle tissue that can be attenuated by HBO.

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