Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Belgium.
Shock. 2011 Jun;35(6):542-9. doi: 10.1097/SHK.0b013e3182115e6a.
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 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 < 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 (PaO2/FiO2 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.
严重败血症尽管血流动力学复苏似乎充分，但常伴有微循环异常。由于血清血管紧张素Ⅱ水平升高可能在该功能障碍中发挥作用，我们在感染性休克的实验模型中评估了依那普利拉的微循环作用。在向腹腔内注射 1.5 克/公斤体重的粪便后 1 小时，16 只麻醉、机械通气的成年雌性绵羊随机接受 2.5 毫克依那普利拉或生理盐水。当出现对液体无反应性低血压（平均动脉压，<65mmHg）时，给予去甲肾上腺素直至最大剂量 3μg·kg(-1)·min(-1)。使用侧流暗场视频显微镜评估舌下微循环。使用 20μm 的截止值来区分小血管和大血管。实验一直进行到绵羊自然死亡或最长 30 小时。在休克和去甲肾上腺素输注的前 2 小时内，安慰剂组中小灌注血管的比例和小血管的微血管血流指数均显著且持续下降（均为趋势 P<0.01），而依那普利拉的给药可预防这些变化。在治疗组和安慰剂组之间，在总体血流动力学变量、休克时间或中位生存时间（21.8[18.6-28.8]与 22.9[21.8-30.0]小时；P=0.45）方面均无差异。然而，在治疗组中，氧交换更差（PaO2/FiO2 比值，224[128-297]与 332[187-450]；P<0.05），且肌酐浓度升高更明显（从 0.51[0.42-0.75]至 1.19[0.64-1.50]mg·dL(-1)；P=0.04），而在对照组中（从 0.55[0.45-0.62]至 0.78[0.46-1.78]mg·dL(-1)；P=0.12）。因此，依那普利拉在这种液体复苏、高动力型感染性休克模型中预防了舌下微循环变量的恶化，而对动脉压无显著影响，但可能对肾功能和肺功能有有害影响。
