Sublingual microcirculatory effects of enalaprilat in an ovine model of septic shock

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 s...

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Veröffentlicht in:Shock (Augusta, Ga.) Ga.), 2011-06, Vol.35 (6), p.542-549
Hauptverfasser: Salgado, Diamantino Ribeiro, He, Xinrong, Su, Fuhong, de Sousa, Dalton Barros, Penaccini, Laura, Maciel, Leonardo Kfuri, Taccone, Fabio, Rocco, José Rodolfo, Silva, Eliézer, De Backer, Daniel, Vincent, Jean-Louis
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container_end_page 549
container_issue 6
container_start_page 542
container_title Shock (Augusta, Ga.)
container_volume 35
creator Salgado, Diamantino Ribeiro
He, Xinrong
Su, Fuhong
de Sousa, Dalton Barros
Penaccini, Laura
Maciel, Leonardo Kfuri
Taccone, Fabio
Rocco, José Rodolfo
Silva, Eliézer
De Backer, Daniel
Vincent, Jean-Louis
description 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,
doi_str_mv 10.1097/SHK.0b013e3182115e6a
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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, &lt;65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 μg·kg(-1)·min(-1). The sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 μm 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 &lt; 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). 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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, &lt;65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 μg·kg(-1)·min(-1). The sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 μm was used to differentiate small and large vessels. Experiments were pursued until the sheep's spontaneous death or for a maximum of 30 h. 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However, oxygen exchange was worse (PaO2/FiO2 ratio, 224 [128-297] vs. 332 [187-450]; P &lt; 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.</abstract><cop>United States</cop><pmid>21283060</pmid><doi>10.1097/SHK.0b013e3182115e6a</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source Journals@OVID; MEDLINE; Elektronische Zeitschriftenbibliothek - Freely accessible e-journals; Journals@Ovid Complete
subjects Angiotensin II - antagonists & inhibitors
Animals
Enalaprilat - therapeutic use
Female
Fluid Therapy
Microcirculation - drug effects
Mouth Floor - blood supply
Placebos
Random Allocation
Sheep, Domestic
Shock, Septic - drug therapy
title Sublingual microcirculatory effects of enalaprilat in an ovine model of septic shock
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