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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Angiogenic factors have been the focus of a great deal of research for the treatment of ischemic diseases. Described just more than 10 years ago, angiopoietin 1 (Ang-1) has shown promising results in I/R models. ⋯ Because of its role in maturation of vessels, it seems well suited to complement the angiogenic factor vascular endothelial growth factor (VEGF), which has been shown to induce vascular budding but in isolation produces nonfunctional vessels. This review will focus on (1) Ang-1 and its receptor, Tie-2, and the resultant intracellular signaling cascade; (2) the complex relationship of Ang-1 and VEGF; (3) the results of Ang-1 in I/R and sepsis models; (4) the results of combination (Ang-1 and VEGF) therapies in I/R and sepsis models; and (5) delivery mechanisms for angiogenic factors to ischemic heart.
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The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. ⋯ Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P < 0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.
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The vascular growth factor angiopoietin 2 (Ang-2) is known to promote inflammation and endothelial dysfunction, but its prognostic capacity and relationship to outcomes in human sepsis are unknown. This is a prospective observational cohort study of 66 patients newly admitted to a tertiary care medical intensive care unit (ICU), which included ICU patients with no sepsis (n = 20) as well as those with sepsis (n = 10), severe sepsis (n = 12), and septic shock (n = 24). ⋯ In the septic cohort, circulating Ang-2 levels were significantly higher (P = 0.01) in those who died (24.9 ng/mL; interquartile range, 21.5-38.0 ng/mL) compared with those who survived (13.5 ng/mL; interquartile range, 8.1-21.6 ng/mL). Elevated circulating serum Ang-2 levels are associated with increased hospital mortality in patients with sepsis.
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Blunt chest trauma resulting in pulmonary contusion with an accompanying acute inflammatory response is a common but poorly understood injury. We previously demonstrated that toll-like receptor 2 (TLR-2) participates in the inflammatory response to lung injury. We hypothesized that the TLR-4, in an MyD88-dependent manner, may also participate in the response to lung injury. ⋯ We further demonstrated that these responses to pulmonary contusion were dependent on MyD88, an adapter protein in the signal transduction pathway mediated by TLRs. These results show that TLRs have a primary role in the response to acute lung injury. Lung inflammation and systemic innate immune responses are dependent on TLR activation by pulmonary contusion.
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Loss of intestinal barrier function after burn injury allows movement of intraluminal contents across the mucosa, which can lead to the development of distant organ injury and multiple organ failure. Tight junction function is highly regulated by membrane-associated proteins including occludin and zonula occludens protein 1 (ZO-1), which can be modulated by systemic inflammation. We hypothesized that (1) burn injury leads to gut barrier injury, and (2) phosphodiesterase inhibition will attenuate these burn-induced changes. ⋯ Confocal microscopy demonstrates that PTX attenuates the burn-induced reorganization of occludin and ZO-1 away from the tight junction. Pentoxifylline attenuates burn-induced intestinal permeability and decreases the breakdown and reorganization of intestinal occludin and ZO-1. Therefore, phosphodiesterase inhibition may be a useful adjunct strategy in the attenuation of burn-induced gut barrier injury.