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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Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. ⋯ To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.
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Sepsis is characterized by systemic inflammation with release of a large amount of inflammatory mediators. If sustained, this inflammatory response can lead to multiple organ failure and/or immunoparalysis. In the latter condition, the host may be susceptible to opportunistic infections or be unable to clear existing infections. ⋯ It also suggests that LXA4 reduced systemic inflammation and NF-κB activation without compromising host defense. Increased macrophage recruitment was in part due to a direct effect of LXA4 as LXA4 increased peritoneal macrophage recruitment in sham controls and partly due to reduced production of IL-10 as LXA4 decreased macrophage IL-10 release (a known inhibitor of macrophage migration) after CLP. The results suggest that LXA4 increased survival in sepsis by simultaneously reducing systemic inflammation as well as bacterial spread.
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Previous animal and human studies have suggested that total plasma sulfide plays a role in the pathophysiology of shock. This study's aim was to determine the value of total plasma sulfide as a marker of shock severity in nonsurgical adult patients admitted to the ICU. Forty-one patients, with various types of shock (septic, cardiogenic, obstructive, and hypovolemic), were included in the study, with an average total plasma sulfide concentration of 23.2 ± 26.3 µM. ⋯ Area under the receiver operating characteristic for total plasma sulfide as a predictor of ICU mortality was 0.739 (confidence interval, 0.587-0.892; P = 0.009). Even after correcting for APACHE II score and lactate values, total plasma sulfide correlated with mortality (odds ratio, 1.058; 95% confidence interval, 1.001-1.118; P = 0.045). The study provides evidence that, in nonsurgical adult ICU patients admitted because of any type of shock, total plasma sulfide correlates with administered norepinephrine dose at admission, severity of disease (APACHE II score ≥30 points), and survival outcome.
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Activated protein C (aPC) promotes fibrinolysis while inhibiting coagulation and inflammation. In septic patients, aPC levels are depleted, and aPC treatment has emerged as a therapeutic option. To better understand the mechanism(s) by which aPC improves survival in sepsis, we sought to determine the effect of aPC treatment on hepatic vasoactive gene and protein expression, leading to changes in hepatic vascular responsiveness in a septic animal model. ⋯ This approach demonstrated aPC significantly improved hepatic perfusion index in the animals that underwent cecal ligation and puncture in the absence of significant changes in portal venous pressure. Furthermore, although aPC did not affect ET-1-dependent sinusoidal vasoconstriction, aPC induced hepatoprotective effects via enhanced red blood cell velocity. Collectively, these data demonstrate aPC ameliorates ET-1-dependent changes in hepatic microcirculation and improves hepatic function in the setting of sepsis.
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Intestinal ischemia-reperfusion (I/R) injury is a well-established animal model of systemic inflammation and can lead to multiple organ failure as well as severe and lasting morbidity and even death. It can occur in humans as a result of vascular surgery or as secondary sequelae to many common conditions including low blood pressure, myocardial infarction, and necrotizing enterocolitis. Systemic inflammation induced through kidney I/R injury has been shown previously to lead to encephalopathic adverse effects, and it was theorized that intestinal injury would also cause secondary central nervous system effects. ⋯ There was a significant increase in brain edema observed in sham-operated animals as well as in fasted and nonfasted I/R groups, but neurons were not apoptotic, in the 6-h time period. Conversely, Iba1-expressing activated microglia cells and glial fibrillary acidic protein-expressing astrocytes were found to be markedly increased in fasted and nonfasted I/R mice compared with controls and sham-operated animals. These data demonstrate that intestinal I/R injury induces inflammatory changes in the brain.