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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Recent studies have demonstrated that intralipid (ILP) conferred myocardial protection against ischemia-reperfusion (IR) injury through activation of reperfusion injury salvage kinase (RISK) pathway. As RISK signal has been shown to be impaired in hypertrophied myocardium, we investigated whether ILP-induced cardiac protection was maintained in hypertrophied rat hearts. Transverse aortic constriction was performed on male Sprague-Dawley rats to induce left ventricular hypertrophy, then sham-operated or hypertrophied rat hearts were isolated and perfused retrogradely by the Langendorff for 30 min (equilibration) followed by 40 min of ischemia and then 120 min of reperfusion. ⋯ In contrast, ischemic preconditioning increased the phosphorylation of Akt, ERK1/2 and GSK3β, improved heart pump function, and reduced myocardial necrosis in sham-operated hearts, a phenomenon partially attenuated by ventricular hypertrophy. Interestingly, GSK inhibitor SB216763 conferred cardioprotection against IR injury in sham-operated hearts, but failed to exert cardioprotection in hypertrophied myocardium. Our results indicated that ventricular hypertrophy abrogated ILP-induced cardioprotection against IR injury by alteration of RISK/GSK3β signal.
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Autophagy plays a protective role in endotoxemic mice. Heat shock factor 1 (HSF-1) also plays a crucial protective role in endotoxemic mice by decreasing inflammatory cytokines. The purpose of this study was to determine whether HSF-1 is involved in attenuating the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated mice and peritoneal macrophages (PMs) through regulating autophagy activity. ⋯ Interestingly, LPS-induced release of inflammatory cytokines did not further increase in HSF-1(-/-) PMs treated with 3-MA but aggravated in HSF-1(+/+) PMs. Lipopolysaccharide-induced autophagy did not decrease in HSF-1(-/-) PMs treated with 3-MA but decreased in HSF-1 PMs(+/+). Taken together, our results suggested that HSF-1 attenuated the release of inflammatory cytokines induced by LPS by regulating autophagy activity.
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Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. ⋯ Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.
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The mortality for acute respiratory distress syndrome (ARDS) remains unacceptably high. Success in clinical trials has been limited, resulting in a lack of effective therapies to treat the syndrome. The projected increase in mechanically ventilated patients and global need for critical care services suggests that the clinical and research landscape in ARDS can no longer be confined to the intensive care unit. ⋯ Furthermore, the ED is an entry point for many of the highest-risk patients for ARDS development and progression. These facts, combined with prolonged lengths of stay in the ED, suggest that the ED could represent a window of opportunity for treatment and preventive strategies, as well as clinical trial enrollment. This review aims to discuss some of the potential strategies that may prevent or alter the trajectory of ARDS, with a focus on the potential role the ED could play in reducing the burden of this syndrome.
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Randomized Controlled Trial Multicenter Study
Plasma First in the Field for Postinjury Hemorrhagic Shock.
Hemorrhage is the most preventable cause of death in civilian and military trauma, and despite tremendous advances in patient transport in the field, survival within the first hour has changed little over the past 40 years. The pathogenesis of trauma-induced coagulopathy is multifactorial, but most authorities believe there is an early depletion of clotting factors. ⋯ The rationale includes the possibility that plasma-first resuscitation may be advantageous beyond direct effects on clotting capacity. The study design is based on a ground ambulance system that allows rapid prehospital thawing of frozen plasma.