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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The authors aimed to clarify the effects of hypercapnic acidosis and its timing on gastric mucosal oxygenation in a canine model of hemorrhage. This was designed as a prospective, controlled, randomized animal study set in a university research laboratory. Five chronically instrumented dogs were used. ⋯ Initial effects of hemorrhage in THE were comparable to CON (DO2 from 11 ± 2 mL·kg⁻¹·min⁻¹ to 8 ± 1 mL·kg⁻¹·min⁻¹; μHbO2 from 56% ± 7% to 43% ± 9%), but after application of hypercapnic acidosis, baseline levels were restored (DO2 10 ± 3 mL·kg⁻¹·min⁻¹; μHbO2 52% ± 14%). Hypercapnic acidosis applied before or after hemorrhage (THE) preserves microvascular mucosal oxygenation. If these experimental findings may be transferred to the clinical setting, deliberate hypercapnic acidosis could serve to augment oxygenation of the splanchnic region in states of compromised circulation, e.g., hemorrhage.
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To investigate the molecular mechanism underlying heme oxygenase-1 (HO-1)-modulated infiltration of neutrophils, the sepsis model of cecal ligation and puncture in Sprague-Dawley rats was used. In vivo induction and suppression of HO-1 were performed by pretreatment with cobalt protoporphyrin IX (CoPP) and zinc protoporphyrin IX, respectively. Tricarbonyldichlororuthenium(II) dimer, [Ru(CO)₃Cl₂]₂ (a carbon monoxide [CO] releaser), and hemoglobin (a CO scavenger) were used to examine the participation of HO-1/CO in the effect of CoPP pretreatment on formylated peptide (fMLP)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation. ⋯ Moreover, anisomycin diminished the suppressive effects of CoPP pretreatment on fMLP-induced migration, actin polymerization, polarization, and migration speed of neutrophils. These results suggest that HO-1 in neutrophil attenuates its infiltration during sepsis via the inactivation of p38 MAPK. Understanding the mechanism that diminishes neutrophil infiltration by HO-1 may help prevent hepatic failure during sepsis.
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Clinical Trial
Apheresis of activated leukocytes with an immobilized polymyxin B filter in patients with septic shock.
In this study, we examined the effects of direct hemoperfusion through filters with immobilized polymyxin B (PMX-DHP) on leukocyte function and plasma levels of cytokines in patients with septic shock. We found that PMX-DHP caused increased expression of C-X-C chemokine receptor 1 (CXCR1) and CXCR2, along with decreased expression of CD64 and CD11b, by circulating neutrophils in patients with septic shock. Plasma levels of cytokines, including interleukin 6 (IL-6), IL-8, IL-10, and high-mobility group box 1, were elevated in patients with septic shock compared with healthy controls, but cytokine levels were not altered by PMX-DHP. ⋯ Neutrophils isolated from the blood after ex vivo PMX perfusion caused less damage to an endothelial cell monolayer than cells from sham-treated blood, whereas neutrophil phagocytosis of opsonized Escherichia coli was unaffected. These results indicate that PMX-DHP selectively removes activated neutrophils and reduces the ability of circulating cells to cause endothelial damage. Selective removal of activated neutrophils using PMX-DHP may improve the systemic inflammatory response in patients with septic shock.
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Comparative Study
Peritoneal negative pressure therapy prevents multiple organ injury in a chronic porcine sepsis and ischemia/reperfusion model.
Sepsis and hemorrhage can result in injury to multiple organs and is associated with an extremely high rate of mortality. We hypothesized that peritoneal negative pressure therapy (NPT) would reduce systemic inflammation and organ damage. Pigs (n = 12) were anesthetized and surgically instrumented for hemodynamic monitoring. ⋯ Our data suggest NPT efficacy is partially due to an attenuation of peritoneal inflammation by the removal of ascites. However, the exact mechanism needs further elucidation. The clinical implication of this study is that sepsis/trauma can result in an inflammatory ascites that may perpetuate organ injury; removal of the ascites can break the cycle and reduce organ damage.