Abstract
Background The aim of this study was to determine the optimal salvage time window within which ischemic postconditioning can be used to ameliorate ischemia/reperfusion (I/R) injury in skeletal muscle.
Methods A total of 48 Sprague–Dawley rats were divided into two groups: I/R only (control) and I/R with postconditioning. Subgroups were divided by duration of ischemia (2, 4, 6, and 8 hours). A pedicled gracilis muscle model was used. The postconditioning protocol consisted of six cycles of 15 seconds of reperfusion followed by 15 seconds of ischemia (total time = 3 minutes). Muscles were harvested 24 hours after I/R injury to examine tissue viability, histology, myeloperoxidase activity, and protective gene expression.
Results Postconditioning groups showed improved muscle viability after 4 and 6 hours of ischemia time as compared with controls (p < 0.05). Higher expression of mitochondrial complexes I, II, III, endothelial nitric oxide synthase, inducible nitric oxide synthase, and Bcl-2 were observed in the postconditioning group after 4 and 6 hours of ischemia (p < 0.05). Lower expression of tumor necrosis factor-α and caspase 3 was observed in the postconditioning group at 4 hours (p < 0.05). Myeloperoxidase activity was similar in both groups at all-time points except 8 hours ischemia, where the control group had higher activity (p < 0.05).
Conclusion Results of this study demonstrate that the effective time window within which postconditioning is most effective for the salvage of skeletal muscle is between 4 and 6 hours of ischemia. Postconditioning offered improved mitochondrial and vascular function with decreased inflammation and cell death. This may be clinically useful as a postinjury salvage technique to attenuate I/R injury after 4 to 6 hours of ischemia.
Keywords
ischemia-reperfusion injury - ischemic postconditioning - skeletal muscle - replantation - free tissue transfer - salvage time window
