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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We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. ⋯ In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.
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Randomized Controlled Trial Clinical Trial
Pentoxifylline decreases the incidence of multiple organ failure in patients after major cardio-thoracic surgery.
We assessed the safety and efficacy of intravenous pentoxifylline [3,7-dimethyl-1-(5-oxohexyl)-xanthine] in patients at risk for developing multiple organ failure after major cardio-thoracic surgery in a single-center, randomized, placebo-controlled study. Of 816 consecutive patients who underwent major cardio-thoracic surgery, 40 who had Acute Physiology and Chronic Health Evaluation II score values > or = 19 at the first postoperative day after the surgery were included. Patients were randomized to receive either placebo (control; n = 25) or intravenous pentoxifylline treatment (pentoxifylline; n = 15) at a dosage of 1.5 mg/kg/h as an adjunct to standard supportive therapy. ⋯ Mortality was 33% in the pentoxifylline group and 36% among control group patients. In conclusion, supplemental pentoxifylline treatment may decrease the incidence of multiple organ failure in patients at risk of systemic inflammatory response syndrome after cardiac surgery. Additional studies are required to determine the validity of the observed effects.
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Postoperative hemodynamic disturbances in obstructive jaundice are associated with complications such as shock and renal failure. Gut-derived endotoxemia may underlie these complications. Recently, we have shown that cholestyramine treatment prevents gut-derived endotoxemia in bile duct-ligated (BDL) rats (Houdijk APJ, Boermeester MA, Wesdorp RIC, Hack CE, van Leeuwen PAM: Tumor necrosis factor unresponsiveness following surgery in bile duct-ligated rats. Am J Physiol 271: G980-G986, 1996). ⋯ Gut endotoxin restriction using cholestyramine treatment maintained normal blood pressure, improved splanchnic blood flow, and completely prevented the fall in renal blood flow in BDL rats. Reducing the gut load of endotoxin in patients with obstructive jaundice scheduled for abdominal surgery may prevent postoperative hemodynamic complications.
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Diaspirin Cross-linked Hemoglobin (DCLHb), a hemoglobin-based oxygen carrier, improves regional blood circulation and systemic hemodynamics in normal and hemorrhaged rats. The action of DCLHb is partly mediated by its scavenging effect on nitric oxide. This study was undertaken to determine the effect of DCLHb on nitric oxide mechanism in hemorrhagic conditions. ⋯ L-arginine pretreatment did not affect DCLHb-induced resuscitation of hemorrhaged rats. Furthermore, L-NAME (pretreated or co-administered) attenuated the resuscitative effect of DCLHb. These data suggest that nitric oxide mechanism may not be the only mechanism involved in the resuscitative effect of DCLHb.
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Hypertonic saline (HS) resuscitation after hemorrhage and sepsis has been shown to markedly reduce the development of lung injury in animals, compared with traditional resuscitation with lactated Ringer's (LR). These experiments examined the effect of HS on lung injury after hemorrhage without sepsis. The effects of HS and LR resuscitation on neutrophil trafficking, neutrophil adhesion, and neutrophil oxidative burst were studied. ⋯ HS animals had less lung injury than LR animals. The mean myeloperoxidase activity in HS versus LR animals was 1.79+/-1.33 U/100 mg versus 3.0+/-1.33 U/100 mg, respectively. The percentage of neutrophils in the bronchoalveolar lavage fluid of HS animals (3.8%+/-.8) was significantly less than that of LR animals (10.8%+/-2.1). This corresponded to a significantly higher peripheral blood neutrophil count in HS animals compared with LR animals, 41% vs. 20%, respectively. There was no difference in neutrophil expression of the CD11b integrin between the HS and LR groups. The neutrophils of LR animals had basal H2O2 production that was 107% greater than that of controls; HS suppressed this hemorrhage-induced activation by > 60%. HS resuscitation after hemorrhagic shock protects against the development of lung injury. This protection is due, in part, to suppression of the hemorrhage-induced neutrophil oxidative burst. HS resuscitation offers immunomodulatory potential after hemorrhagic shock.