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
-
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.
-
Na/H exchanger 1 (NHE1) is a ubiquitously expressed protein on mammalian plasma membranes and involved in cell apoptosis and tissue injury. Our previous study found that NHE1 inhibition prevents burn-induced acute lung injury (ALI). However, the potential mechanism of NHE1 in burn-induced ALI is still unclear. ⋯ The data demonstrate that NHE1 activation facilitates burn-induced endothelial cell apoptosis, mediated by Ca-dependent pathway. PI3K-Akt and p38 MAPK were found to be upstream regulators of NHE1. This study provides new mechanisms underlying burn-induced ALI.
-
Clinical Trial Observational Study
Association between doppler snuffbox resistive index and tissue perfusion in septic patients.
Peripheral vascular disorders leading to tissue hypoperfusion play a central role in the pathophysiology of organ failure in septic shock. The Doppler snuffbox resistive index (SBRI) can be an accurate parameter to evaluate the status of peripheral vasculature at the bedside. We evaluated whether the SBRI is related to lactate levels or the peripheral perfusion index (PI) and its ability to predict lactate clearance in septic patients. ⋯ The Doppler SBRI is correlated with tissue perfusion parameters in critically ill patients. An abnormal SBRI may be better than the PI for predicting poor lactate clearance in septic patients. Further investigations are required to determine whether correcting an abnormal SBRI and PI may improve the success rate of septic shock resuscitation.
-
Septic patients are often anemic, requiring red blood cell (RBC) transfusions. However, RBC transfusions are associated with organ injury. The mechanisms of RBC-induced organ injury are unknown, but increased clearance of donor RBCs from the circulation with trapping in the organs could play a role. We hypothesized that washing of RBCs prior to transfusion may reduce clearance and trapping of donor cells and thereby reduce organ injury. ⋯ In healthy recipients, washing increased 24h-PTR of donor RBCs and decreased trapping in organs. In pneumoseptic rats, washing reduced bacterial outgrowth and lung injury, but did not improve PTR.
-
We performed a systematic review and meta-analysis of studies investigating the end-expiratory occlusion (EEO) test induced changes in cardiac index (CI) and in arterial pressure as predictors of fluid responsiveness in adults receiving mechanical ventilation. ⋯ EEO test is accurate to predict fluid responsiveness in semirecumbent or supine patients but not in prone patients. EEO test exhibited higher specificity in patients ventilated with low tidal volume, and its accuracy is better when its hemodynamic effects are assessed by direct measurement of CI than by the arterial pressure.