Secondary Burn Progression Decreased by Erythropoietin*

Tobalem, Mickaël; Harder, Yves; Rezaeian, Farid; Wettstein, Reto

doi:10.1097/ccm.0b013e318275cee7

Cited by 32 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ischemic musculocutaneous skin flaps, Epo administration up-regulates eNOS and the protective effect is abrogated by administration of eNOS inhibitors ( 56 ). Administration of Epo has also been shown to reduce the depth and area of secondary burn progression ( 57 ). These extra-hematopoietic eNOS dependent protective actions may result, at least in part, from vasodilation with increased blood flow.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

et al. 2014

View full text Add to dashboard Cite

Background: Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS).Methods: Using laser Doppler flow imaging, CBF was monitored in wild-type (WT) and eNOS-deficient mice undergoing controlled cortical impact followed by administration of Epo (5000 U/kg) or normal saline.Results: Cerebral blood flow decreased in all groups post-injury with the greatest reductions occurring at the impact site. Epo administration resulted in significantly higher CBF in the peri-contusional sites in the WT mice [70.2 ± 3.35% in Epo-treated compared to 53 ± 3.3% of baseline in saline-treated mice (p < 0.0001)], but no effect was seen in the eNOS-deficient mice. No CBF differences were found at the core impact site where CBF dropped to 20–25% of baseline in all groups.Conclusion: These differences between eNOS-deficient and WT mice indicate that the Epo mediated improvement in CBF in traumatic brain injury is eNOS dependent.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In our review, several studies over the last five years examined the role of erythropoietin (EPO), a hormone with known anti-inflammatory, angiogenic, and vasodilatory properties [74–76], in the prevention and treatment of burn wound progression [75]. Tobalem et al demonstrate that treatment with EPO limits interspace necrosis and burn depth extension in a dose-dependent manner in a comb burn model [76].…”

Section: Discussionmentioning

confidence: 99%

“…Turkaslan et al investigated the effects of HBOT in the zone of stasis and reported increased cells in the synthesis stage by 24 hours post-burn, increased radioactive uptake by 5 days post-burn, and decreased necrosis overall in the treatment group [75]. Similar to the study by Tobalem et al [93, 94], new vessel formation was not significantly different between the treatment and control group in the early critical stages of burn wound progression, suggesting a less important role for neoangiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Current concepts on burn wound conversion—A review of recent advances in understanding the secondary progressions of burns

Salibian

Rosario

Severo

et al. 2016

Burns

102

View full text Add to dashboard Cite

Burn wound conversion describes the process by which superficial partial thickness burns convert into deeper burns necessitating surgical intervention. Fully understanding and thus controlling this phenomenon continues to defy burn surgeons. However, potentially guiding burn wound progression so as to obviate the need for surgery while still bringing about healing with limited scarring is the major unmet challenge. Comprehending the pathophysiologic background contributing to deeper progression of these burns is an essential prerequisite to planning any intervention. In this study, a review of articles examining burn wound progression over the last five years was conducted to analyze trends in recent burn progression research, determine changes in understanding of the pathogenesis of burn conversion, and subsequently examine the direction for future research in developing therapies. The majority of recent research focuses on applying therapies from other disease processes to common underlying pathogenic mechanisms in burn conversion. While ischemia, inflammation, and free oxygen radicals continue to demonstrate a critical role in secondary necrosis, novel mechanisms such as autophagy have also been shown to contribute affect significantly burn progression significantly. Further research will have to determine whether multiple mechanisms should be targeted when developing clinical therapies.

show abstract

“…73,76 In 2012, Tobalem et al 77 reported that the early treatment of burns with systemic EPO prevented secondary burn progression by improving vascular perfusion within the endangered area in a dose-dependent manner. In a follow-up study, the same investigators 78 reported that increased iNOS expression and suppression of the inflammatory response were the underlying mechanisms of EPO's preventative actions on secondary burn progression. Interestingly, Bohr et al 79 reported that EPO derivatives that can trigger EPO-mediated signaling but do not bind to the EPOR homodimer, such as the helix β-surface peptide (ARA290), can reduce burn depth and area and protect burn wounds from deteriorating in mice with a skin burn.…”

Section: Epo and Wound Healing: Animal Study Findingsmentioning

confidence: 96%

“…reported that the early treatment of burns with systemic EPO prevented secondary burn progression by improving vascular perfusion within the endangered area in a dose‐dependent manner. In a follow‐up study, the same investigators reported that increased iNOS expression and suppression of the inflammatory response were the underlying mechanisms of EPO's preventative actions on secondary burn progression. Interestingly, Bohr et al .…”

Section: Epo and Wound Healing: Animal Study Findingsmentioning

confidence: 98%

Erythropoietin, a novel repurposed drug: An innovative treatment for wound healing in patients with diabetes mellitus

Hamed

Bennett

Demiot

et al. 2013

Wound Repair Regeneration

View full text Add to dashboard Cite

Developing a new drug is expensive: the cost of going from bench to bedside is about $US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits. Recombinant erythropoietin (EPO) is a potential candidate for repurposing because the results of numerous studies have shown that systemic and topical EPO is therapeutically beneficial when it is administered to healthy and diabetic animals with acute and chronic skin wounds and burns. Moreover, the molecular mechanisms of EPO's actions have been elucidated: EPO acts on those nonhematopoietic cells which are involved in the innate immune response where it promotes cellular proliferation and differentiation, exerts its cytoprotective actions, and inhibits apoptosis. In this review, the mechanism of EPO's action in skin wound healing is reviewed, and its potential for treating acute and chronic skin wounds and stimulating tissue regeneration in diabetic patients is discussed.

show abstract

Secondary Burn Progression Decreased by Erythropoietin*

Abstract: Erythropoietin represents an easy-to-use therapeutic approach to prevent secondary burn progression, i.e., to control damage after burn injury. It preserves microcirculatory perfusion within the endangered areas in a dose-dependent manner.

Cited by 32 publications

References 29 publications

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

Current concepts on burn wound conversion—A review of recent advances in understanding the secondary progressions of burns

Erythropoietin, a novel repurposed drug: An innovative treatment for wound healing in patients with diabetes mellitus

Contact Info

Product

Resources

About