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 objective of the study was to evaluate the tissue oxygenation and hemodynamic effects of NOS inhibition in clinical severe septic shock. Eight patients with septic shock refractory to volume loading and high level of adrenergic support were prospectively enrolled in the study. Increasing doses of NOS inhibitors [N(G)-nitro-L-arginine-methyl ester (L-NAME) or N(G)-monomethyl-L-arginine (L-NMMA)] were administered as i.v. bolus until a peak effect = 10 mmHg on mean blood pressure was obtained or until side effects occurred. ⋯ Blood lactate and the difference between tonometric gastric and arterial PCO2 remained unchanged. There were 4/8 ICU survivors. We conclude that nitric oxide synthase inhibition in severe septic shock was followed with a progressive correction of the vasoplegic hemodynamic disturbances with finally normalization of cardiac output and systemic vascular resistances without any demonstrable deterioration in tissue oxygenation.
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Septic shock is characterized by a decrease in systemic vascular resistance. Nevertheless, regional increases in vascular resistance can occur that may predispose mammals to organ dysfunction, including the acute respiratory distress syndrome. In the host infected by endotoxin (lipopolysaccharide, LPS), the expression and release of proinflammatory tumor necrosis factor-alpha (TNFalpha) rapidly increases, and this cytokine production is regulated by agents elevating cyclic AMP. ⋯ In addition, pretreatment of mice with terbutaline also improves the survival in a model of severe endotoxemia. The infiltration of polymorphonuclear neutrophils into organs (e.g., lung and liver) from the surviving LPS mice treated with terbutaline was reduced almost to that seen in the normal controls. These findings suggest that the inhibition of TNFalpha and NO (via iNOS) production as well as the increment of IL-10 production contribute to the beneficial effect of terbutaline in animals with endotoxic shock.
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Comparative Study
Distinct effects of systemic infusion of G-CSF vs. IL-6 on lung and liver inflammation and injury in hemorrhagic shock.
Production of pro-inflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) occurs at multiple tissue sites in hemorrhagic shock (HS), resulting in elevated circulating plasma levels. The current study was designed to test the hypothesis that circulating G-CSF and IL-6 contribute to polymorphonuclear neutrophilic granulocyte (PMN)-mediated inflammation and organ injury in HS. Sprague-Dawley rats were subjected to decompensated HS (mean arterial blood pressure = 40 mm Hg for 2.5 h), followed by resuscitation with lactated Ringer's solution with or without G-CSF (3 microg/kg) or IL-6 (3 microg/kg). ⋯ Infusion of IL-6, in contrast, dramatically decreased inflammation and injury in both the lung and liver; the anti-inflammatory effects of IL-6 may be mediated, in part, by down-modulation of nuclear factor (NF)-kappaB activity. Thus, circulating G-CSF and IL-6 have opposing effects on PMN recruitment and injury in the lung in HS while both protect against hepatic necrosis. The beneficial effect of these cytokines on liver injury in HS appears to be independent of PMN recruitment.
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Gastric mucosal-arterial PCO2 gradient (P(g-a)CO2) is used to assess splanchnic perfusion and oxygenation. We evaluated whether P(g-a)CO2 reflects whole body (Q) and splanchnic (Qsp) blood flow, oxygen delivery (DO2) and consumption (VO2) after coronary artery by pass graft (CABG) operation. Thirty patients received dobutamine or dopexamine to increase cardiac index, 15 patients enalapril or sodium nitroprusside to lower blood pressure, and 30 patients were controls. ⋯ Increased splanchnic blood flow (0.65 +/- .19 vs. 0.94 +/- .31 L/min/m2, P < 0.001) and increased splanchnic DO2 (101 +/- 28 vs. 143 +/- 42 mL/min/m2, P < 0.001) during catecholamine infusions were associated with increased P(g-a)CO2 (8 +/- 8 vs. 11 +/- 7 mmHg, P = 0.003). P(g-a)CO2 does not reflect whole body or splanchnic blood flow, DO2 or VO2 after CABG operations. The physiology of P(g-a)CO2 is complex and therefore it is difficult for clinicians to interpret changes in gastric mucosal-arterial PCO2 gradient in individual patients after cardiac surgery.
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Comparative Study
Does the timing of hypertonic saline resuscitation affect its potential to prevent lung damage?
Hypertonic saline (HS) resuscitation has been reported to prevent lung damage by suppressing neutrophil activation in animal models. Data on the effectiveness of HS to prevent organ damage in the clinical setting are inconsistent. We investigated whether the timing of HS administration relative to neutrophil activation could affect its potential to block neutrophil responses. ⋯ HS treatment caused a transient state of suppression during which neutrophil activation was suppressed; however, HS was unable to suppress cells that were stimulated with fMLP before HS was added. Accordingly, in vivo lung damage was greater in animals that received HS after they had been partially resuscitated with LR compared to mice that received HS before LR (P < 0.05). We conclude that timing of exposure to HS affects neutrophil responses in vitro and may reduce the potential of HS resuscitation to prevent lung injury in vivo.