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Activated protein C restores kidney function in endotoxin-induced acute renal failure in the rat

Introduction

Activated protein C (APC) has been shown to have beneficial effects on the inflammatory process and coagulation during sepsis. Inflammation and coagulopathy impair the microvasculature and therefore disturb oxygen transport to the tissue. The hypothesis of our study was that APC treatment improves renal microvascular oxygenation and kidney function in endotoxin-induced acute renal failure in the rat.

Methods

In 18 anesthetized and ventilated (FiO2 0.4) male Wistar rats, the arterial blood pressure and renal blood flow were recorded. The renal microvascular PO2 was continuously measured by phosphorescence lifetime technique. All animals received a lipopolysaccharide (LPS) bolus (10 mg/kg) to induce endotoxemic shock. All rats received fluid resuscitation (hydroxyethyl starch 130 kDa) 1 hour after LPS application. In one group of animals, APC (drotrecogin alpha, Xigris®; Lilly) was continuously infused in a concentration of 10 μg/kg/hour. Another group received a continuous infusion of 100 μg/kg/hour APC.

Results

Data are presented in Figure 1.

Figure 1
figure1

FR = fluid resuscitation; T0 = baseline; t1 = 1 hour after LPS bolus; t2 = resuscitation (3 hours); MAP = mean arterial pressure; RBF = renal blood flow; RVR = renal vascular resistance; CLcrea = creatinine clearance; cμPO 2 = cortical microvascular PO 2 ; mμPO 2 = medullary microvascular PO 2 .

Conclusion

APC at a concentration of 100 μg/kg/hour significantly restored kidney function compared with standard fluid resuscitation during endotoxemia. This application best improved the mean arterial pressure. APC had no beneficial effects, however, on the average renal microvascular PO2.

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Almac, E., Johannes, T., Mik, E. et al. Activated protein C restores kidney function in endotoxin-induced acute renal failure in the rat. Crit Care 13, P356 (2009). https://doi.org/10.1186/cc7520

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Keywords

  • Starch
  • Arterial Blood Pressure
  • Renal Blood Flow
  • Hydroxyethyl
  • Fluid Resuscitation