Recombinant Human Erythropoietin Influences Revascularization and Healing in a Rat Model of Random Ischaemic Flaps

Abstract

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin

“…Among these pleiotropic effects, EPO accelerates wound healing and modulates cognitive function. For example, EPO has been observed to promote incisional wound closure in rodent models by reducing ischemic and reperfusion injury, mobilizing endothelial progenitor cells, augmenting angiogenesis, and decreasing inflammation (35). To determine whether pHBSP could also provide benefits in wound healing, we examined its effect in the healing of punch biopsy wounds.…”

Erythropoietin as an antiapoptotic, tissue-protective cytokine

“…73 The skin has also been shown to be protected by EPO in rodent flap models. 76,77 In these studies, the tissue-protective effects appear to depend strongly on the dose and treatment duration, suggesting that tissues may vary in their responses to EPO.…”

Nonerythropoietic Tissue Protective Compounds Are Highly Effective Facilitators of Wound Healing

“…Among the pleiotropic effects of EPO reported, a number of investigators have reported significant activity of EPO in promoting the healing of ischemic raised cutaneous skin flaps (10)(11)(12)(13)(14), ischemiareperfusion in random musculocutaneous flaps (15), incisional wounds (10,13), and in colonic anastomoses (16,17). Additionally, skin thermal burns also have been reported to respond in a beneficial way to EPO (18).…”