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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Comparative Study Clinical Trial Observational Study
Prognosis Value of Early Veno Arterial PCO2 Difference in Patients Under Peripheral Veno Arterial Extracorporeal Membrane Oxygenation.
Veno arterial membrane oxygenation (VA ECMO) is increasingly used for cardiogenic failure. However, hemodynamic targets for adequate resuscitation remain a challenge. The PCO2 gap and the ratio between PCO2 gap and the arteriovenous difference in oxygen (PCO2 gap/Da-vO2) are marker of peripheral hypoperfusion. We hypothesized that the PCO2 gap and the PCO2 gap/Da-vO2 ratio might be useful parameters in VA ECMO patients. ⋯ Early PCO2 gap and PCO2 gap/Da-vO2 ratio are higher in the early death group in patients under VA ECMO.
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Comparative Study
Superior Effects of Nebulized Epinephrine to Nebulized Albuterol and Phenylephrine in Burn and Smoke Inhalation-Induced Acute Lung Injury.
The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously, we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. ⋯ Epinephrine and phenylephrine groups significantly reduced trachea wet-to-dry weight ratio and lung vascular endothelial growth factor-A level compared with control group. Histopathologically, epinephrine group significantly reduced lung severity scores and preserved vascular endothelial-cadherin level in pulmonary arteries. In conclusion, the results of our studies suggest that nebulized epinephrine more effectively ameliorated the severity of BSI-ALI than albuterol or phenylephrine, possibly by its combined α1- and β2-agonist properties.
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Adrenomedullin is a vasoactive peptide that improves endothelial barrier function in sepsis, but may also cause hypotension and organ failure. Treatment with a non-neutralizing monoclonal anti-adrenomedullin antibody showed improvement in murine sepsis models. We tested the effects of the humanized monoclonal anti-adrenomedullin antibody Adrecizumab in a porcine two-hit model of hemorrhagic and septic shock. ⋯ After induction of sepsis, plasma adrenomedullin increased immediately in both the groups, but increased quicker and more pronounced in the antibody group. In this two-hit shock model, treatment with an anti-adrenomedullin antibody significantly increased plasma adrenomedullin levels, while significantly less animals developed septic shock and renal granulocyte extravasation was significantly reduced. Thus, therapy with Adrecizumab may provide benefit in sepsis, and clinical investigation of this drug candidate is warranted.
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Hepatic ischemia/reperfusion (I/R) injury is a major concern in liver surgery settings. Mitochondria are critical targets or the origin of tissue injury, particularly I/R injury. Mitophagy, a selective form of autophagy, is a fundamental process that removes damaged or unwanted mitochondria for mitochondrial quality control, but its role in hepatic I/R remains unclear. ⋯ No significant change is in PINK1 but it translocated to MAMs region to initiate mitophagy. The silencing PINK1 by shRNA in cultured primary hepatocytes reduced the level of H/R-induced mitophagy, leading to the accumulation of dysfunctional mitochondria during H/R, increased production of ROS, mitochondria-induced apoptosis, and eventually hepatocyte death. Taken together, these findings indicate that PINK1-mediated mitophagy plays a key role in mitochondrial quality control and liver cell survival during I/R.
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Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. ⋯ Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.