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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In this study, experiments were designed to determine whether microRNAs (miRNAs) play a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based therapeutics may provide a unique opportunity to translate this knowledge into the clinical setting. ⋯ Transfection of H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA and protein levels of interleukin 10 and increased expression of nuclear factor κB and its downstream cytokines during hypoxia/reperfusion injury, could activate caspase 3 and apoptosis. Our study demonstrated the altered expression of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The involvement of miRNAs in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues for cardiac protection strategies during cardiac surgery.
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Our previous study has demonstrated that hypertonic saline (HS) given at 3 h after cecal ligation and puncture (CLP) surgery alleviates circulatory failure, multiple organ dysfunction syndrome, and mortality rate in rats. However, only few data exist on the application of HS in acid-base and electrolyte imbalance of sepsis. In addition, early one-dose HS administration seems to have only modest improvement on mortality rate. ⋯ However, only the two-dose HS administration significantly improved hyponatremia and hypocalcemia in septic rats. Beneficial effects of HS in septic rats may be attributed to not only reducing plasma levels of NO and IL-1β, but also improving metabolic acidosis and electrolyte imbalance. In addition, two-dose HS administration could reverse electrolyte imbalance caused by CLP.
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It is not clear why some patients with aspiration advance to acute lung injury or acute respiratory distress syndrome, whereas others do not. The Western diet is high in advanced glycation end-products (AGEs), which have been found to be proinflammatory. We hypothesize that dietary AGEs exaggerate the pulmonary inflammatory response following gastric aspiration. ⋯ In conclusion, a diet high in AGEs exacerbates acute lung injury following gastric aspiration as evidenced by increases in neutrophil infiltration, airway albumin leakage, and decreased pulmonary compliance. This is the first evidence implicating exacerbation of acute inflammatory lung injury by dietary AGEs. Targeting AGEs in the circulatory system may offer a therapeutic strategy for limiting lung injury following gastric aspiration.
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Combination therapy with molecular hydrogen and hyperoxia in a murine model of polymicrobial sepsis.
Sepsis is the most common cause of death in intensive care units. Some studies have found that hyperoxia may be beneficial to sepsis. However, the clinical use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. ⋯ However, combination therapy with H2 and hyperoxia had a more beneficial effect against lung, liver, and kidney damage of moderate or severe CLP mice. Furthermore, we found that the beneficial effect of this combination therapy was associated with the decreased levels of oxidative product (8-iso-prostaglandin F2α), increased activities of antioxidant enzymes (superoxide dismutase and catalase) and anti-inflammatory cytokine (interleukin 10), and reduced levels of proinflammatory cytokines (high-mobility group box 1 and tumor necrosis factor α) in serum and tissues. Therefore, combination therapy with H2 and hyperoxia provides enhanced therapeutic efficacy via both antioxidant and anti-inflammatory mechanisms and might be potentially a clinically feasible approach for sepsis.
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Forty percent of trauma deaths are due to hemorrhage, with 33% to 56% occurring in the prehospital environment. This study proposes a new index (NI) based on the ratio of serum lactate concentration (LC) to peripheral perfusion (PP) as an indicator of hemorrhage-induced mortality during the prehospital stage. Thirty-six anesthetized rats were randomized into three groups according to volume of controlled blood loss. ⋯ The correlation coefficients with mortality for NI, SI, PP, SBP, MAP, PPR, DBP, TEMP, LC, RR, and HR were -0.818, -0.759, 0.726, 0.721, 0.694, 0.662, 0.597, 0.544, -0.487, 0.420, and -0.296, respectively, with the same order as the AUC. NI was shown to be an optimal independent mortality predictor on multivariable logistic regression analysis. In conclusion, the newly proposed hemorrhage-induced mortality index, based on blood lactate/PP ratio, was a better marker for predicting mortality in rats undergoing acute hemorrhage in comparison to the other parameters evaluated in this study.