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.