Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Tc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI). Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. ⋯ Neither of the treatments had an effect on Kf at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.
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Splenectomy is controversial in acute hemorrhagic shock models. ⋯ Splenectomy likely accounts for the transient increase in hematocrit and the higher HR in SP swine prior to hemorrhage, and the differences in TBV removed between the two groups during hemorrhage. With a fixed end point model using a moderate rate of acute hemorrhage and an MAP of 40 mm Hg, splenectomy is not necessary and may confound results.
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Trauma represents a remarkable social and economical burden, being a leading cause of death and morbidity in the young population. The Endothelial Glycocalyx (EG) is a web of membrane bound to the luminal side of the blood vessels endothelium. Its role includes maintenance of the vascular permeability barrier and mediation of shear response. ⋯ With this review we initially explore the role of the EG in the microcirculatory dysfunction associated with trauma. Subsequently, we investigate the impact of fluid administration on the EG, including its potential of protecting the microcirculation from the detrimental effects of trauma. Particular emphasis is reserved to the role of inflammatory modulation and sensible fluid resuscitation.
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Alternate erythropoietin (EPO)-mediated signaling via the EPOR/CD131 heteromeric receptor exerts the tissue-protective actions of EPO in a wide spectrum of injuries, especially ischemic diseases. Circulating endothelial progenitor cells contribute to endothelial repair and post-natal angiogenesis after chronic ischemic injury. This work aims to investigate the effects of ARA290, a specific agonist of EPOR/CD131 complex, on a subpopulation of endothelial progenitor cells named endothelial colony-forming cells (ECFCs) and to characterize its contribution to ECFCs-induced angiogenesis after peripheral ischemia. ⋯ ARA290 induces specific improvement of the biological activity of ECFCs. ARA290 administration in combination with ECFCs has a synergistic effect on post-ischemic angiogenesis in vivo. This potentiation appears to rely, at least in part, on a CD31-dependent increase in homing of the transplanted cells to the ischemic tissue.
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Nitric oxide (NO) likely plays a pivotal role in the pathogenesis of sepsis. Arginine is a substrate for NO, whereas the methylated arginines-asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)-are endogenous by-products of proteolysis that inhibit NO production.We investigated if high-plasma levels of ADMA, SDMA, and arginine/ADMA ratio were associated with 90-day mortality in patients with severe sepsis or septic shock. ⋯ High levels of ADMA and SDMA in plasma were associated with increased 90-day mortality in patients with severe sepsis or septic shock. Interfering with the methylarginine-NO systems may be a novel target in these patients.