NONRESUSCITATED ENDOTOXEMIA INDUCES MICROCIRCULATORY HYPOXIC AREAS IN THE RENAL CORTEX IN THE RAT

The pathophysiology of acute renal failure (ARF) in sepsis is only partly understood. In several animal models of septic ARF, no profound tissue hypoxia or decrease in microcirculatory Po-2 (mu Po-2) can be seen. We hypothesized that heterogeneity of microcirculatory oxygen supply to demand in the kidney is obscured when looking at the average mu Po-2 during endotoxemia. In 20 anesthetized and ventilated rats, MAP, renal blood flow (RBF), and creatinine clearance (CLcrea) were recorded. Renal mu Po-2 was measured by phosphorescence quenching, allowing measurement of mu Po-2 distributions. Five animals received a 1-h LPS infusion (10 mg kg(-1) h(-1)). In 5 rats, RBF was mechanically reduced to 2.1 +/- 0.2 mL min(-1). Five animals served as time control. LPS infusion significantly reduced RBF to 2.1 +/- 0.2 mL min(-1) and induced anuria. Average cortical mu Po-2 decreased from 68 +/- 4 to 52 +/- 6 mmHg, with a significant left shift in the cortical oxygen histogram toward hypoxia. This shift could not be observed in animals receiving mechanical RBF reduction. In these animals, CLcrea was reduced to 50%. An additional group of rats (n = 5) received fluid resuscitation. In these animals, RBF was restored to baseline, CLcrea increased approximately 50%, and the cortical microcirculatory hypoxic areas disappeared after resuscitation. In conclusion, endotoxemia was associated with the occurrence of cortical microcirculatory hypoxic areas that are not detected in the average Po-2 measurement, proving the hypothesis of our study. These observations suggest the involvement of hypoxia in the pathogenesis of endotoxemia-induced ARF.