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Pressure-controlled hemorrhagic shock in mice: a new model of acute kidney injury
Critical Care volume 14, Article number: P522 (2010)
At the present time, mice models have failed to reproduce human acute kidney injury (AKI) and new relevant models of AKI are required . In this study we developed a model of AKI in mice based on pressure-controlled hemorrhagic shock that closely reproduces hypotension involved in most of human ischemic AKI.
We first determined shock and resuscitation modalities in a C57/Bl6 mice population. A femoral arterial catheter was used for pressure control and bleeding and a central jugular catheter for anesthesia and resuscitation. We secondly explored renal repercussions of a 2-hour shock duration at 35 mmHg mean arterial pressure. We assessed successively the glomerular filtration rate (GFR), histological kidney injury score and performed real-time PCR after the procedure. The shock group was compared with sham mice and with a control group that underwent no procedure (n = 5 in each group).
The shock group GFR was decreased 2 (D2) and 6 (D6) days after shock when compared with control and sham (Figure 1). This AKI was intrinsic as showed by the Na/K urinary ratio increase and the decrease in urine concentration ability. Tissular damage prevailed in the outer medulla with a maximal expression at D6 (paucicellular tubular epithelium, intratubular casts) (Figure 2). These lesions are associated with an increase of tissular KIM-1 and HIFs mRNA. Despite GFR normalization, the shock group showed discreet defect in urine concentration ability and a slight peritubular fibrosis 3 weeks after shock.
This new model of AKI based on hypotension opens new perspectives in the field of short-term and long-term kidney function following AKI.
Rosen S, et al.: J Am Soc Nephrol. 2008., 19:
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Mayeur, N., Minville, V., Jaafar, A. et al. Pressure-controlled hemorrhagic shock in mice: a new model of acute kidney injury. Crit Care 14, P522 (2010). https://doi.org/10.1186/cc8754
- Glomerular Filtration Rate
- Acute Kidney Injury
- Outer Medulla
- Shock Group
- Sham Mouse