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Ann Thorac Surg 2003;75:184-189
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

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

^a Heart Care Associates, Milwaukee Heart Institute, Milwaukee, Wisconsin, USA
^b Lenox Hill Heart and Vascular Institute, Cardiovascular Research Foundation, New York, New York, USA

Accepted for publication July 26, 2002.

* Address reprint requests to Dr Kipshidze, Lenox Hill Heart and Vascular Institute, 130 East 77th St, Black Hall, 9th Floor, New York, NY 10021, USA.
e-mail: nkipshidze{at}lenoxhill.net

BACKGROUND: Iron 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.

METHODS: The 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.

RESULTS: Conventional, 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.

CONCLUSIONS: Local application of deferoxamine mesylate enhances neovascularization and recovery of surgically induced skeletal muscle ischemia in a sheep model.

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