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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Myocardial injury in adult, pediatric, and newborn patients is a leading cause of mortality and morbidity. Although the underlying etiologies are different among patient populations, the sequence of initial ischemic-hypoxic injury followed by secondary myocardial reperfusion injury is relatively consistent. Overall infarct size is important because it is believed to be a key determinant of mortality. ⋯ Multiple adult animal models have demonstrated the protective effects of cyclosporine in ischemia-reperfusion. A recent human pilot clinical trial also reported reduced myocardial injury and infarct size in patients treated with cyclosporine intravenously before percutaneous coronary intervention for ST-elevation myocardial infarction. Despite the paucity of evidence of cyclosporine A demonstrating myocardial protection in pediatric and newborn patients, the existing animal experimental results are promising.
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We hypothesize that the nebulization of γ-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome will effectively improve pulmonary function following burn and smoke inhalation after 96 h. Adult ewes (n = 14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 h after the injury (g-T group, n = 6), whereas the control group (n = 5) was nebulized with only ethanol. ⋯ The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9 ± 0.87 vs. 4.6 ± 1.4, P < 0.05), and bronchiolar obstruction (2.0% ± 1.1% vs. 4.6% ± 1.7%, P < 0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn- and smoke-injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of acute lung injury patients who have sustained oxidative damage to the airway.
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After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study, we hypothesized that multiple trauma results in immediate activation, consumption, and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality. ⋯ Key fluid-phase inhibitors of complement, such as C4b-binding protein and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronical rapid activation and dysfunction of complement, suggesting a trauma-induced complementopathy early after injury. These events may participate in the impairment of the innate immune response observed after severe trauma.
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Despite our increasing ability to support vital organs and resuscitate patients, the morbidity and mortality of acute kidney injury (AKI) remain high in the intensive care unit (ICU). The ability to predict the occurrence of AKI is crucial for the development of preventive strategies. Early diagnosis of AKI requires markers that are sensitive and easily applicable in clinical practice. ⋯ The Doppler-based renal resistive index, which is a simple, rapid, noninvasive, and repeatable marker, could be a promising tool to prematurely detect the patients most at risk of developing AKI in the ICU and to distinguish transient from persistent AKI. Moreover, the resistive index could also be useful to adjust preventive or therapeutic modalities for the kidney perfusion at the bedside. The recent progress in ultrasound with contrast-enhanced ultrasound gives the opportunity to assess not only the kidney macrocirculation but also the kidney microcirculation in the ICU.
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Expression of inflammatory cytokines is regulated by transcriptional and posttranscriptional mechanisms. We previously showed that NADPH oxidase-derived superoxide induces inflammatory mediators in response to tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS). In this study, we examined the role of endothelial NADPH oxidase in the regulation of mRNA stability of three inflammatory mediators: interleukin (IL) 8, IL-6, and intercellular adhesion molecule 1 (ICAM-1). ⋯ In conclusion, NADPH oxidase contributes to destabilization of IL-8 mRNA stability and propose a model for the complex underlying mechanism, which is dependent upon agonist (LPS vs. TNF-α) and target molecule (IL-8 vs. IL-6 and ICAM-1) and involves tristetraprolin, p38, and extracellular signal-regulated kinase 1/2 MAPK.