Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice
| Autor: | Otmar Trentz, Guido A. Wanner, Michael D. Menger, Claudio Contaldo, Ahmed Elsherbiny, Christoph A. Meier, Yves Harder |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Reperfusion Injury/pathology/physiopathology/prevention & control Physiology Ischemia Inflammation Vascular permeability Microcirculation Mice Physiology (medical) Internal medicine medicine Erythropoietin/administration & dosage Animals Blood Flow Velocity/drug effects Muscle Skeletal Erythropoietin Skin Back ddc:617 Dose-Response Relationship Drug business.industry Muscle Skeletal/blood supply/drug effects/physiopathology medicine.disease Microcirculation/drug effects/pathology/physiopathology Recombinant Proteins Surgery Mice Inbred C57BL Endocrinology Reperfusion Injury Circulatory system medicine.symptom Cardiology and Cardiovascular Medicine business Perfusion Blood Flow Velocity Intravital microscopy medicine.drug |
| Zdroj: | American Journal of Physiology. Heart and Circulatory Physiology, Vol. 293, No 1 (2007) pp. H274-83 |
| ISSN: | 0363-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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