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Authors: Salgado, Diamantino Ribeiro
He, Xinrong
Su, Fuhong
Sousa, Dalton Barros de
Penaccini, Laura
Maciel, Leonardo Kfuri
Taccone, Fabio
Rocco, Jose Rodolfo
Silva, Eliezer [UNIFESP]
De Backer, Daniel
Vincent, Jean-Louis
Univ Libre Bruxelles
Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Albert Einstein Hosp
Keywords: Angiotensin II
renal function
sublingual microcirculation
Issue Date: 1-Jun-2011
Publisher: Lippincott Williams & Wilkins
Citation: Shock. Philadelphia: Lippincott Williams & Wilkins, v. 35, n. 6, p. 542-549, 2011.
Abstract: Severe sepsis is frequently associated with microcirculatory abnormalities despite seemingly adequate hemodynamic resuscitation. As increased serum angiotensin II levels may play a role in this dysfunction, we evaluated the microcirculatory effects of enalaprilat in an experimental model of septic shock. One hour after injection of 1.5 g/kg body weight of feces into the abdominal cavity, 16 adult female anesthetized, mechanically ventilated sheep were randomized to receive 2.5 mg enalaprilat or saline. When fluid-resistant hypotension (mean arterial pressure, <65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 mu the sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 mu m was used to differentiate small and large vessels. Experiments were pursued until the sheep's spontaneous death or for a maximum of 30 h. There were progressive and significant reductions in the proportion of small perfused vessels and in the microvascular flow index for small vessels (both P < 0.01 for trend) during shock and the first 2 h of norepinephrine infusion in the placebo group, which were prevented by the administration of enalaprilat. There were no differences between treated and placebo groups in global hemodynamic variables, time to shock or median survival time (21.8 [18.6-28.8] vs. 22.9 [21.8-30.0] h; P = 0.45). However, oxygen exchange was worse (PaO(2)/FIO(2) ratio, 224 [128-297] vs. 332 [187-450]; P < 0.05), and creatinine concentrations increased more in the treated group (from 0.51 [0.42-0.75] to 1.19 [0.64-1.50] mg.dL(-1); P = 0.04) than in the control group (from 0.55 [0.45-0.62] to 0.78 [0.46-1.78] mg.dL(-1); P = 0.12), Enalaprilat therefore prevented the worsening of sublingual microcirculatory variables in this fluid-resuscitated, hyperdynamic model of septic shock, without significant effect on arterial pressure, but with a possible deleterious effect on renal and lung function.
ISSN: 1073-2322
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