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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FTY720 is a sphingosine 1 phosphate (S1P) receptor agonist approved for the treatment of multiple sclerosis, which is a chronic inflammatory autoimmune disorder. Sepsis is a complex syndrome associated with progressive endotoxemic developments, which finally leads to damage of multiple organs, including the heart. In critical patients, cardiovascular dysfunction due to sepsis is a major cause of death. ⋯ Additionally, the activation of protein kinase B and extracellular signal-regulated kinase 1/2 could be inhibited by the S1P1 and S1P3 receptor antagonist vulcanized polyethylene23019. Therefore, we infer that S1P exerts a protective effect towards endotoxic cardiomyocytes by decreasing the levels of TNF-α and IL-6, regulating apoptotic and survival signaling pathway. The S1P1 and S1P3 receptors are involved in the prosurvival signal activation.
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Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular comorbidity. ⋯ However, hyperoxia decreased cardiac tissue three-nitrotyrosine formation (P < 0.001) and inducible nitric oxide synthase expression (P = 0.016). Ultimately, survival did not differ significantly either. In conclusion, in contrast to our previous study in swine with coronary artery disease, hyperoxia did not beneficially affect cardiac function or tissue injury in healthy swine, but was devoid of deleterious side effects.
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Dysfunction of the gut-blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein. ⋯ In an in-vitro model, stimulation of human colon epithelial cells with peptidoglycan, but not with lipopolysaccharide, resulted in elevated secretion of pro-inflammatory cytokines, reflecting inflammatory activity of the intestinal epithelium. Taken together, PT and HS lead to increased permeability of the gut-blood barrier. Bacterial components may lead to production of inflammatory and chemotactic mediators by gut epithelial cells, underlining the role of the gut as an immunologically active organ.
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Editorial
Perfluorocarbon Gas Transport: an Overview of Medical History With Yet Unrealized Potentials.
Perfluorocarbon (PFCs) compounds have been a hereto fore under realized pharmaceutical class of intravenous emulsions and respiratory adjuvants researched extensively since the late 1970. This review represents an introduction for a series of more detailed lectures/manuscripts that were part of a combined United States collaborative Federal agency meeting in early February, 2017 at Ft Detrick, MD, focused upon potential technologies in development to fulfill a perceived need: "When blood transfusion is not available." As such, PFCs represent a distinctly different class of pharmaceutical artificial oxygen (and other gas) transporters than are hemoglobin-based oxygen carriers (HBOCs). ⋯ The PFCs should be viewed as pharmaceuticals possessing unique gas solubility and diffusion characteristics such that they may relieve ischemia of tissues with low/flow-no flow states therefore they can enhance tissue salvage while other definitive treatments are being sought. PFCs as short-term enhanced tissue oxygen (and other gas enhancements) delivery vehicles should have varied and potentially game-changing medical potentials.