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Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice

Contaldo, Claudio
Elsherbiny, Ahmed
Trentz, Otmar
Menger, Michael D
Wanner, Guido A
Published in American journal of physiology. Heart and circulatory physiology. 2007, vol. 293, no. 1, p. H274-83
Abstract Erythropoietin (EPO) has been proposed as a novel cytoprotectant in ischemia-reperfusion (I/R) injury of the brain, heart, and kidney. However, whether EPO exerts its protection by prevention of postischemic microcirculatory deterioration is unknown. We have investigated the effect of EPO on I/R-induced microcirculatory dysfunctions. We used the mouse dorsal skinfold chamber preparation to study nutritive microcirculation and leukocyte-endothelial cell interaction in striated muscle of the dorsal skinfold by in vivo fluorescence microscopy before 3 h of ischemia and during 5 days of reperfusion. Animals were pretreated with EPO (5,000 U/kg body wt) 1 or 24 h before ischemia. Vehicle-treated I/R-injured animals served as controls. Additional animals underwent sham operation only or were pretreated with EPO but not subjected to I/R. I/R significantly (P < 0.05) reduced functional capillary density, increased microvascular permeability, and enhanced venular leukocyte-endothelial cell interaction during early reperfusion. These findings were associated with pronounced (P < 0.05) arteriolar constriction and diminution of blood flow during late reperfusion. Pretreatment with EPO induced EPO receptor and endothelial nitric oxide synthase expression at 6 h of reperfusion (P < 0.05). In parallel, EPO significantly (P < 0.05) reduced capillary perfusion failure and microvascular hyperpermeability during early reperfusion and arteriolar constriction and flow during late reperfusion. EPO pretreatment substantially (P < 0.05) diminished I/R-induced leukocytic inflammation by reducing the number of rolling and firmly adhering leukocytes in postcapillary venules. EPO applied 1 h before ischemia induced angiogenic budding and sprouting at 1 and 3 days of reperfusion and formation of new capillary networks at 5 days of reperfusion. Thus our study demonstrates for the first time that EPO effectively attenuates I/R injury by preserving nutritive perfusion, reducing leukocytic inflammation, and inducing new vessel formation.
Keywords AnimalsBackBlood Flow Velocity/drug effectsDose-Response Relationship, DrugErythropoietin/administration & dosageMiceMice, Inbred C57BLMicrocirculation/drug effects/pathology/physiopathologyMuscle, Skeletal/blood supply/drug effects/physiopathologyRecombinant ProteinsReperfusion Injury/pathology/physiopathology/prevention & controlSkin
PMID: 17337594
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Research group Groupe Pittet Cuenod Brigitte (chirurgie plastique et reconstructive) (96)
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CONTALDO, Claudio et al. Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice. In: American journal of physiology. Heart and circulatory physiology, 2007, vol. 293, n° 1, p. H274-83. doi: 10.1152/ajpheart.01031.2006 https://archive-ouverte.unige.ch/unige:34866

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Deposited on : 2014-03-20

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