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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Inadequate splanchnic perfusion, detected as a low gastric intramucosal pH (pHi), in the face of normal systemic perfusion predicts an increased risk for multiple organ failure after trauma. Although the exact etiology of this low pHi is unknown, angiotensin II is thought to be an important regulator of gut perfusion during and after resuscitation from shock. The purpose of this study is to determine whether enalaprilat, an angiotensin-converting enzyme inhibitor, improves gut perfusion in critically injured patients. ⋯ In examining the determinants of pHi, the intramucosal-arterial PCO2 difference was improved after enalaprilat administration (27 +/- 6 to 17 +/- 3 mmHg, p = .04) while no difference was observed in arterial bicarbonate (19.5 +/- .7 to 19.7 +/- .8, p = .90). Additionally, the change in pHi observed with enalaprilat correlated with predrug intramucosal-arterial PCO2 difference (r = .74, r2 = .55, p = .0005). These results demonstrate that enalaprilat improves gut perfusion as measured by gastric tonometry in critically injured patients, and that this effect appears to be independent of changes in systemic perfusion.
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The role of nitric oxide (NO) in hepatic oxygen transport is unclear. We investigated the effects of aminoethyl-isothiourea (AE-ITU), a selective inhibitor of iNOS activity, on liver blood flow and oxygen consumption (VO2H) in the pig. Endotoxin (lipopolysaccharide, LPS) was given intraportally (1.7 microg/kg/h), followed by AE-ITU (10 mg/kg) after 3 h (n = 7), LPS controls (n = 8) received LPS for 6 h. ⋯ After injection of AE-ITU during LPS infusion, CO was unchanged, while Q(HA) increased gradually from 127 +/- 20 to 268 +/- 40 mL/min over 3 h (p < .05) and DO2H from 38 +/- 5 to 60 +/- 5 mL/in (p < .05). ERO2H increased from .54 +/- .04 to .69 +/- .03 in 30 min, while VO2H increased from 23 +/- 4 to 35 +/- 3 mL/in in 3 h (p < .05). Thus, AE-ITU restored hepatic arterial blood flow and increased hepatic oxygen consumption in pigs with endotoxemia.
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Neutrophils are of great importance for the host's defense against invading organisms. Granulocyte colony-stimulating factor (G-CSF) has been used to augment both the neutrophil number and function, and its prophylactic administration has proved beneficial in animal models of sepsis. However, pretreatment with G-CSF is not practical under clinical conditions. We therefore investigated the effect of recombinant human (rh)G-CSF, administered only after infection, on the survival rate as well as the hemodynamic and cytokine response of the animals. ⋯ These data suggest that treatment with rhG-CSF after the onset of bacterial sepsis might not significantly improve the chances of survival for non-neutropenic patients.
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Comparative Study
Comparison of hypertonic with isotonic saline hydroxyethyl starch solution on oxygen extraction capabilities during endotoxic shock.
Hypertonic colloid solutions reportedly exert protective effects on the microcirculation. The present study investigated the effects of a hypertonic saline hydroxyethyl starch (HES) solution on the oxygen extraction capabilities in an endotoxic shock model in the dog. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin before being randomly divided into two groups to receive a 4 mLkg infusion in 10 min of either hypertonic (7.5%, n = 7), or isotonic (.9%, n = 7) HES solution. ⋯ There were no significant differences in blood gases or lactate concentrations between the groups. When cardiac tamponade was induced to study the tissue oxygen extraction capabilities, hypertonic saline HES-treated dogs had a slightly lower critical oxygen delivery (11.1+/-1.6 vs. 14.2+/-3.3 mL/kg x min, p = NS), and a significantly higher critical oxygen extraction ratio (61.9+/-17.1 vs. 44.0+/-11.5%, p < .05) than the isotonic group. We conclude that during endotoxic shock in dogs, hypertonic saline HES solution can increase whole body oxygen extraction capabilities, probably by an improvement in microvascular perfusion in septic conditions.
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Randomized Controlled Trial Clinical Trial
Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline.
The influence of coronary artery bypass grafting (CABG) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 as well as its modulation by pentoxifylline (PTF) were studied in a prospective, randomized, double-blinded study. 12 patients undergoing elective CABG were randomly assigned to receive either saline or PTF (1 mg/kg as a loading dose followed by 1 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after CABG, and (C) 24 h after CABG. Cytokine plasma levels as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA expression in peripheral blood mononuclear cells. ⋯ However, application of PTF during CABG neither inhibited the spontaneous production of IL-10 nor modulated cytokine production ex vivo. These results suggest a biphasic response of stimulated peripheral blood mononuclear cell cytokine gene expression during CABG with an initial tolerance to LPS stimulation. The application of PTF during CABG in doses that are primarily based on its use in occlusive arterial disease do not seem to modulate the release of the cytokines studied.