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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Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study. ⋯ The smoke inhalation alone had a little or no effect on these variables. This model closely mimics hyperdynamic human sepsis. The excessive production of NO may be extensively involved in the pathogenic process.
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Gut epithelial cells are important in orchestrating immunoinflammatory responses in the gut and may impact systemic immunocompetent cells after shock and trauma. Ethanol (EtOH) intoxication is an important etiological factor in trauma and may increase the likelihood of posttraumatic septic complications. Both EtOH and gut I/R impair intestinal barrier function. ⋯ Lastly, the findings in apoptosis mirror the data of the TNF production in the apical compartment. Ethanol and H/R have a synergistic effect on cytokine production and barrier dysfunction in this model. They may also contribute to increased infectious complications and posttraumatic organ failure.
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Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. ⋯ Arterial bicarbonate contributes more to pHi than the DeltapCO2 but is not associated with mortality. Hyperventilation partly masks mucosal acidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome.
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Microvascular failure is a major determinant for the development of hepatocellular dysfunction after hemorrhagic shock. Induction of heme oxygenase (HO) 1 may confer hepatocellular protection. Hemin arginate (HAR) induces HO-1 and protects against shock-induced organ failure. ⋯ Hemin arginate pretreatment significantly improved liver microcirculation, reduced NADPH autofluorescence, significantly increased IL-10, and tended to decrease TNF-alpha serum levels compared with shock vehicle. Blockade of the HO pathway with tin-mesoporphyrin-IX after HAR pretreatment abolished the observed beneficial effects, whereas the additional administration of the carbon monoxide donor dichloromethane reversed the tin-mesoporphyrin-IX-mediated changes. These results suggest that HAR pretreatment improves liver microcirculation and mediates an anti-inflammatory cytokine response after hemorrhagic shock through induction of HO-1 and in part through an increased carbon monoxide release.
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It has been shown that the intrinsic mitochondrial apoptotic cascade is activated in vascular hyperpermeability after conditions such as hemorrhagic shock. Studies from our laboratory demonstrated mitochondrial reactive oxygen species (ROS) formation in endothelial cells during vascular hyperpermeability. We hypothesized that the participation of mitochondrial ROS in the intrinsic apoptotic cascade results in microvascular endothelial cell hyperpermeability. ⋯ Complex III inhibitors antimycin A (10 microM) and stigmatellin (10 microM) attenuated BAK (BH3)-mediated ROS formation and hyperpermeability (P<0.05). The complex III inhibition decreased BAK (BH3)-mediated cytochrome c release. The results suggest that mitochondrial ROS formation, particularly at respiratory chain complex III, is involved in BAK-induced monolayer hyperpermeability.