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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Along with redistributive shock, myocardial dysfunction is now recognized as highly prevalent in early severe sepsis. Indeed, aside from their distinct loading potency, resuscitation fluids have been poorly investigated as to their specific molecular impact on myocardial dysfunction. The objective of this study was to evaluate the load-independent biological impact of different resuscitation fluids on endotoxin-induced myocardial dysfunction. ⋯ Hypertonic saline solution was also cardioprotective by early prevention of myocardial dysfunction and by reducing cardiac apoptosis. Fluid infusions have distinct load-independent structural/biological impacts on endotoxin-induced myocardial dysfunction. Albumin and hypertonic saline solution are the most pleiotropic fluids in protecting the heart after a "sepsis" hit.
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Alterations in the activity of vascular K channels are commonly associated with abnormalities in cerebral vascular function after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage-induced vasospasm remains incompletely understood; nevertheless, activation of K channels may be of benefit in relieving spastic constriction. This study was to examine whether the vasodilators KMUP-1 and pinacidil, a KATP-channel opener, have the ability to prevent SAH-induced vasospasm via the large-conductance Ca-activated K (BKCa) channels in cerebral arteries. ⋯ Subarachnoid hemorrhage-induced deficits in motor function and BKCa-channel inhibition were improved by KMUP-1-treated and pinacidil-treated rats. In addition, SAH appears to modify BKCa-channel calcium sensitivity. KMUP-1 and pinacidil prevent SAH-induced vasospasm at least in part by the restoration of BKCa-channel activities.
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Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-oligodeoxynucleotide (ODN) 1826, in cardiac functional recovery after T-H. ⋯ Our data suggest that CpG-ODN significantly attenuates T-H-induced cardiac dysfunction. The mechanisms involve activation of both PI3K/Akt and ERK signaling pathways. The TLR9 agonist, CpG-ODN 1826, may provide a novel treatment strategy for preventing or managing cardiac dysfunction and enhancing recovery in T-H patients.
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Large surface area burn injuries lead to activation of the innate immune system, which can be blocked by parasympathetic inputs mediated by the vagus nerve. We hypothesized that vagal nerve stimulation (VNS) would alter the inflammatory response of peritoneal macrophages after severe burn injury. Male BALB/c mice underwent right cervical VNS before 30% total body surface area steam burn and were compared with animals subjected to burn alone. ⋯ We identified a protective role for VNS in blocking peritoneal macrophage activation. Analysis of the phosphorylation state of nuclear factor κB pathway mediator, p65 Rel A, revealed a VNS-mediated reduction in p65 phosphorylation levels after exposure to LPS compared with burn alone. In combination, these studies suggest VNS mediates the inflammatory response in peritoneal macrophages by affecting the set point of LPS responsiveness.
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Previous studies have shown that PI3K/GSK-3β/β-catenin signaling pathway plays a vital role in ischemic preconditioning. The present study attempts to evaluate whether PI3K/GSK-3β/β-catenin signaling pathway might be responsible for the cardioprotection in ischemic postconditioning. Male Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. ⋯ It was found that Post and SB + I/R reduced infarct size (32.3% [SD, 2.8%], 32.7% [SD, 2.1%], vs. 53.4% [SD, 3.2%], respectively, P < 0.05) and apoptotic index of cardiomyocytes (23.2% [SD, 1.8%], 23.8% [SD, 1.8%], vs. 47.3% [SD, 5.8%], respectively, P < 0.05); compared with I/R, wortmannin abolished the cardioprotection of ischemic postconditioning. Post and SB + I/R increased phosphorylated Akt, phosphorylated GSK3β, β-catenin in cytosol and nucleus, and Bcl-2 expression versus I/R. These results indicate that ischemic postconditioning could induce myocardial protection via PI3K/GSK-3β/β-catenin signaling pathway, activation of which results in accumulation of β-catenin and upregulation of its target genes Bcl-2.