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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Because end-organ injury can occur with reperfusion following hemorrhage or ischemia, we hypothesized that aggressive intravenous fluid resuscitation would aggravate tissue injury in a fixed-volume model of hemorrhagic shock. Unanesthetized chronically prepared male rats were hemorrhaged 33-36 mL/kg for 2.5 h. Then Lactated Ringers Solution (3x hemorrhage volume) was infused over 5 min (FAST), 20 min (MEDIUM), 180 min (SLOW), or not at all (NO RESUS). ⋯ Creatinine at 5 h PR was less in the groups treated with intravenous fluid compared to the NO RESUS group, P < 0.05. Survival at 72 h was reduced in the FAST (57%) and NO RESUS (58%) groups compared to the SLOW (87%) and MEDIUM (85%) groups (P < 0.05). Thus, overly aggressive fluid tx accelerates hepatocellular injury, is no better than lesser rates of resuscitation at correcting plasma lactate and preserving renal function, and provides no overall survival benefit.
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We previously reported direct evidence of respiratory bursting by neutrophils in the pulmonary circulation of endotoxin-infused rats. To evaluate the effect of the protease inhibitor nafamostat mesilate (NM) on leukocyte-mediated radical formation in the pulmonary circulation of rats infused with endotoxin, we observed and measured the number of sticking leukocytes and quantified radical production in the pulmonary circulation of endotoxin-infused rats by means of a fluorescent imaging technique. Plasma C3a (desArg) was also measured using an enzyme-linked immunosorbent assay. ⋯ The number of the leukocytes adhering within pulmonary capillaries, oxygen radical production in the rat pulmonary circulation, and plasma C3a (desArg) were all lower in the NM group than in the Et group. The leukocytes producing oxygen radicals were confirmed to be neutrophils by electron microscopic analysis of cerium deposition. We conclude that NM attenuates plasma C3a formation, neutrophil adherence to pulmonary capillaries, and their production of oxygen radical in rats infused with endotoxin.
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Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. ⋯ These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI.
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We evaluated the hepatic arterial buffer response (HABR) to portal vein (PV) occlusion during 2 h of reduced superior mesenteric arterial blood flow (median 2 mL min(-1) kg(-1), range of 1-3 mL min(-1) kg(-1)) and 1 h of reperfusion in seven pigs and in seven controls. In animals with reduced mesenteric blood flow, celiac trunk blood flow (Qtr) increased during mesenteric hypoperfusion from 4 +/- 1 mL min(-1) kg(-1) (mean +/- SD) to 16 +/- 3 mL min(-1) kg(-1) (P = 0.028), and hepatic arterial blood flow (Qha) increased from 2 +/- 1 to 10 +/- 4 mL min(-1) kg(-1) (P= 0.018). The extra-hepatic fraction of Qtr (Qtr-Qha) also increased (P = 0.028). ⋯ Despite increased cardiac output, all flows from the celiac trunk decreased during reperfusion (P = 0.028) and the HABR partially recovered. We conclude that reduced mesenteric perfusion impairs the HABR, which recovers only partially after reperfusion. The distribution of the increased celiac trunk flow secondary to PV occlusion ranges from increased HABR and decreased non-hepatic blood flow (a steal) to decreased hepatic arterial blood flow and increased non-hepatic blood flow (an inverse steal).
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Interrelation of plasma nitrotyrosine (NT) concentrations in patients of septic shock and their prognosis was examined. Blood samples were obtained from 12 patients during the first episode of septic shock at hospitalization, and their plasma NT concentrations were measured. ⋯ Plasma NT concentrations (means +/- SE) of the non-survivors and survivors were 0.68 +/- 0.13 nmol/mL (n = 7), and 0.21 +/- 0.05 nmol/mL (n = 5), respectively, the former being significantly higher than the latter. The present results suggest that plasma concentration of NT relates to prognosis in human septic shock, although further studies with a larger patient population are necessary for confirmation of the suggestion.