1Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. 2Department of Anesthesia and Intensive Care, ZOL St-Jan, Genk, Belgium. 3Department of Neurosurgery, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.
Crit Care Med. 2014 Feb;42(2):e114-22. doi: 10.1097/CCM.0b013e3182a641b8.
Alterations in cerebral microvascular blood flow may develop during sepsis, but the consequences of these abnormalities on tissue oxygenation and metabolism are not well defined. We studied the evolution of microvascular blood flow, brain oxygen tension (PbO2), and metabolism in a clinically relevant animal model of septic shock.
Prospective randomized animal study.
University hospital research laboratory.
Fifteen invasively monitored and mechanically ventilated female sheep.
The sheep were randomized to fecal peritonitis (n = 10) or a sham procedure (n = 5), and craniectomies were performed to enable evaluation of cerebral microvascular blood flow, PbO2, and metabolism. The microvascular network of the left frontal cortex was evaluated (at baseline, 6, 12, and 18 hr) using sidestream dark-field videomicroscopy. Using an off-line semiquantitative method, functional capillary density and the proportion of small perfused vessels were calculated. PbO2 was measured hourly by a parenchymal Clark electrode, and cerebral metabolism was assessed by the lactate/pyruvate ratio using brain microdialysis; both these systems were placed in the right frontal cortex.
In septic animals, cerebral functional capillary density (from 3.1 ± 0.5 to 1.9 ± 0.4 n/mm, p < 0.001) and proportion of small perfused vessels (from 98% ± 2% to 84% ± 7%, p = 0.004) decreased over the 18-hour study period. Concomitantly, PbO2 decreased (61 ± 5 to 41 ± 7 mm Hg, p < 0.001) and lactate/pyruvate ratio increased (23 ± 5 to 36 ± 19, p < 0.001). At 18 hours, when shock was present, animals with a mean arterial pressure less than 65 mm Hg (n = 6) had similar functional capillary density, proportion of small perfused vessels, and PbO2 values but significantly higher lactate/pyruvate ratio (46 ± 18 vs 20 ± 4, p = 0.009) compared with animals with an mean arterial pressure of 65-70 mm Hg (n = 4).
Impaired cerebral microcirculation during sepsis is associated with progressive impairment in PbO2 and brain metabolism. Development of severe hypotension was responsible for a further increase in anaerobic metabolism. These alterations may play an important role in the pathogenesis of brain dysfunction during sepsis.
脓毒症期间可能会发生脑微血管血流改变，但这些异常对组织氧合和代谢的影响尚不清楚。我们在一种具有临床相关性的脓毒性休克动物模型中研究了微血管血流、脑氧张力 (PbO2) 和代谢的变化。
前瞻性随机动物研究。
大学医院研究实验室。
15 只接受侵入性监测和机械通气的雌性绵羊。
绵羊随机分为粪便性腹膜炎 (n = 10) 或假手术组 (n = 5)，行开颅术以评估大脑微血管血流、PbO2 和代谢。使用侧流暗场视频显微镜评估左侧额皮质的微血管网络（在基线、6、12 和 18 小时）。使用离线半定量方法计算功能毛细血管密度和小灌注血管的比例。通过组织内 Clark 电极每小时测量 PbO2，通过脑微透析评估脑代谢的乳酸/丙酮酸比；这两个系统都放置在右侧额皮质。
在脓毒症动物中，大脑功能毛细血管密度（从 3.1 ± 0.5 降至 1.9 ± 0.4 n/mm，p < 0.001）和小灌注血管的比例（从 98% ± 2%降至 84% ± 7%，p = 0.004）在 18 小时的研究期间逐渐下降。同时，PbO2 降低（61 ± 5 至 41 ± 7 mm Hg，p < 0.001），乳酸/丙酮酸比值升高（23 ± 5 至 36 ± 19，p < 0.001）。在 18 小时休克时，平均动脉压<65 mmHg 的动物（n = 6）的功能毛细血管密度、小灌注血管比例和 PbO2 值相似，但乳酸/丙酮酸比值明显升高（46 ± 18 比 20 ± 4，p = 0.009）与平均动脉压为 65-70 mmHg 的动物（n = 4）。
脓毒症期间大脑微血管循环受损与 PbO2 和脑代谢逐渐受损有关。严重低血压的发展导致无氧代谢进一步增加。这些改变可能在脓毒症期间脑功能障碍的发病机制中发挥重要作用。
