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
-
Despite significant advances in the care of critically ill patients, acute lung injury continues to be a complex problem with high mortality. The present study was designed to characterize early lipopolysaccharide (LPS)-induced pulmonary injury and small interfering RNA targeting focal adhesion kinase (FAK) as a possible therapeutic tool in the septic lung remodeling process. Male Wistar rats were assigned into endotoxemic group and control group. ⋯ There was fibrotic response in the lung characterized by increased amount in total and specific-type collagen. These data may explain the frequent clinical presentation during sepsis of reduced lung compliance, oxygen diffusion, and pulmonary hypertension. The fact that FAK silencing was protective against lung collagen deposition underscores the therapeutic potential of FAK targeting by small interfering RNA.
-
The overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is considered a final common effector in ischemia/reperfusion (I/R) injury. The aim of the current study was to examine the precise time course of the activation of PARP in peripheral leukocytes and the reperfused myocardium tissue on myocardial I/R injury from the same rat and to identify the relationship between myocardial infarct size and the degree of PARP activation in circulating leukocytes. Another aim of the study was to test the effect of 3-aminobenzamide (a well-known and widely used PARP inhibitor) on the activation of PARP in the reperfused myocardium and peripheral leukocytes. ⋯ Immunohistochemical studies localized the staining of PAR primarily to the cardiac myocytes and vascular endothelial cells. At 6 h, there was a significant linear correlation between infarct size and PARP activity, whereas at 2 and 24 h, no relationship was found. The PARP inhibitor 3-aminobenzamide (3-AB, 20 mg kg⁻¹ i.v. injection 15 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced infarct size through depressing the activation of the enzyme in myocytes and peripheral leukocytes even when the treatment is initiated at 2 h after reperfusion.
-
The aim of the current study was to determine whether hypercholesterolemia affects the delayed sevoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury and, if so, the underlying mechanism. Male Sprague-Dawley rats fed 2% cholesterol-enriched chow for 8 weeks were subjected to sevoflurane preconditioning (2.4% vol/vol, 1 h) 24 h before myocardial ischemia was induced by occluding the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The hemodynamic parameters left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rise/fall rate of left ventricular pressure were continuously monitored, and myocardial infarct size was determined at the end of reperfusion. ⋯ The expression of endothelial NOS and Bad did not differ among all groups. The expression of myocardial phosphorylated endothelial NOS, Bcl-2, and phosphorylated Bad in normocholesterolemic rats was not affected by delayed sevoflurane preconditioning but was decreased in the hypercholesterolemic control group, and this was not reversed by sevoflurane, compared with the normocholesterolemic control group. Taken together, these results indicate that sevoflurane preconditioning exerts delayed cardioprotection against IR injury in normocholesterolemic rats, which is blocked by hypercholesterolemia potentially via interference with the iNOS/mitochondrial ATP-dependent K⁺ channel pathway.
-
Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. ⋯ Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.
-
Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.