Deferoxamine enhances neovascularization and recovery of ischemic skeletal muscle in an experimental sheep model

Abstract

BackgroundIron chelators have been reported to interfere with inflammatory cells and possibly enhance vascular growth factor expression. The objective of this study was to investigate the efficacy of the iron chelator deferoxamine mesylate in preventing skeletal muscle ischemia. MethodsThe latissimus dorsi muscle (LDM) was mobilized in 20 adult sheep. Two separate pockets were created in each sheep. Autologous fibrin sealant with or without 100 mg/mL of deferoxamine mesylate (10 pockets) was added to the pockets. Deferoxamine mesylate alone was also applied to another 10 pockets, whereas the 10 other pockets served as controls. ResultsConventional, indirect immunofluorescent en-face staining showed that in nonmobilized, nonischemic LDM the capillary density was 196 ± 14 capillaries/mm2 in the distal and 207 ± 19 capillaries/mm2 in the middle part. After severe ischemic shock (subtotal mobilization), the muscle did not recover completely even after 2 months (149 ± 15 capillaries/mm2 in the distal part and 177 ± 16 capillaries/mm2 in the middle part of the LDM). Fibrin application only increased muscle neovascularization. The number of capillaries per mm2 of muscle increased to 250 ± 25 in the distal part and to 271 ± 24 in the middle part of the LDM. However, when fibrin was applied with added deferoxamine mesylate, the capillary density increased to 361 ± 25 capillaries/mm2 in the distal part (p < 0.05 vs fibrin only; controls) and to 401 ± 20 capillaries/mm2 in the middle part of the LDM (p < 0.05 vs fibrin only and p < 0.001 vs controls). The data are concordant with the blood flow estimation before and after mobilization (severe ischemic shock) in the different parts of the LDM. ConclusionsLocal application of deferoxamine mesylate enhances neovascularization and recovery of surgically induced skeletal muscle ischemia in a sheep model.