1 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia.
2 Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
Am J Respir Crit Care Med. 2016 Sep 15;194(6):692-700. doi: 10.1164/rccm.201511-2285OC.
It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change.
We aimed to determine the nature and extent of changes in renal structure and function over time in an ovine model of septic shock.
Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes.
Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy.
In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.
尚不清楚脓毒性休克如何导致急性肾损伤(AKI),以及这是否与组织学变化有关。
我们旨在确定绵羊脓毒性休克模型中肾结构和功能随时间变化的性质和程度。
15 只绵羊接受了肾动脉流量探针和肾静脉插管的置管。其中 10 只给予静脉内大肠杆菌诱导脓毒性休克,5 只作为对照。动物接受机械通气 48 小时,同时接受方案指导的静脉补液和去甲肾上腺素输注以维持平均动脉压。每隔 24 小时或在动物出现 2 小时少尿时采集肾活检。一位对组织来源不知情的肾脏病理学家通过光镜和电子显微镜对 31 种预先指定的结构变化进行系统地定量组织学外观。
给予大肠杆菌的绵羊发生了脓毒性休克、少尿、血清肌酐升高和肌酐清除率降低(AKI),但两组之间的肾血流无随时间变化(P>0.30)或组内随时间变化(P>0.50)。仅在非脓毒症动物中,肾氧消耗增加(P=0.01),但肾乳酸通量在两组之间无差异(P>0.50)。所有活检均未见明显结构紊乱,尽管某些细胞外观随时间变化,但脓毒症和非脓毒症动物之间唯一的区别是电子显微镜下的系膜扩张。
在重症监护支持的革兰氏阴性脓毒性休克模型中,早期 AKI 与肾血流、氧输送或组织学表现的变化无关。其他机制必须导致脓毒症性 AKI。