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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Remote ischemic preconditioning (RIPC) is one of the most powerful intrinsic cardioprotective strategies discovered so far and experimental data indicate that comorbidity may interfere with the protection by RIPC. Therefore, we investigate whether RIPC-induced cardioprotection was intact in hypercholesterolemic rat hearts exposed to ischemia reperfusion in vivo. Normal or hypercholesterolemic rat hearts were exposed to 30 min of ischemia and 2 h of reperfusion, with or without RIPC, PI3K inhibitor wortmannin, MEK-ERK1/2 inhibitor PD98059, GSK3β inhibitor SB216763. ⋯ In contrast, RIPC failed to reduce myocardial necrosis and apoptosis as well as to increase the phosphorylated Akt and GSK3β in hypercholestorolemic myocardium. Importantly, we found that inhibition of GSK with SB216763 reduced myocardial infarct size in healthy and hypercholesterolemic hearts, but no additional cardioprotective effect was achieved when combined with RIPC. Our results suggest that acute GSK3β inhibition may provide a novel therapeutic strategy for hypercholesterolemic patients during acute myocardial infarction, whereas RIPC is less effective due to signaling events that adversely affect GSK3β.
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Acute Mesenteric Ischemia Among Postcardiac Surgery Patients Presenting with Multiple Organ Failure.
Acute mesenteric ischemia (AMI) is a rare but severe complication after cardiac surgery. However, AMI is likely to be more frequent in the subgroup of patients presenting with multiple organ failure after a cardiac surgery. The primary objective of this study was to identify AMI risk factors among patients requiring intensive care unit (ICU) admission after cardiac surgery. ⋯ AMI is a frequent condition among patients presenting with multiple organ failure after cardiac surgery, occurring in 10% of them. The prognosis of AMI is extremely poor. The main mechanism of AMI is NOMI, occurring in approximately 80% of patients. Further progress should be performed on prevention and earlier diagnosis.
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Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity, and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic shock-induced DIC. ⋯ NEUT-SFL, NETs, and elevated nucleosome concentrations were all correlated to DIC (P <0.05). We have shown that NETosis is significantly correlated to septic shock-induced DIC.
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Galectin-3 is a β-galactoside-binding lectin implicated as a mediator in a variety of inflammatory and fibrotic diseases. However, information about galectin-3 release in patients with acute respiratory distress syndrome (ARDS) is very limited. We sought to determine whether plasma galectin-3 levels were increased in ARDS patients and were associated with disease severity. ⋯ Higher levels of galectin-3 were significantly associated with disease severity and worse outcomes in ARDS patients.
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The monitoring of septic shock induced immunosuppression has been proposed to identify patients who could benefit from specific immunoadjuvant therapies. Among potential biomarkers to monitor immunological status, functional testing remains the gold standard because it directly measures the capacity of a cell population to respond to an immune challenge. We investigated a new approach in intracellular staining for flow cytometry to measure tumor necrosis factor (iTNF) produced in vitro by monocytes in response to lipopolysaccharide. ⋯ These preliminary results illustrate the feasibility of immune functional testing on a routine manner in septic shock patients. They now deserve to be widely assessed and validated in various intensive care unit conditions. This could be a major step to characterize the rapidly changing immune response overtime and thus permit personalized medicine.