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 Po2(μPo2) can be seen. We hypothesized that heterogeneity of microcirculatory oxygen supply to demand in the kidney is obscured when looking at the average 7mu;Po2during endotoxemia. In 20 anesthetized and ventilated rats, MAP, renal blood flow (RBF), and creatinine clearance (CLcrea) were recorded. Renal μPo2was measured by phosphorescence quenching, allowing measurement of nPo2distributions. Five animals received a 1-h LPS infusion (10 mg kg-1h-11). 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-1and induced anuria. Average cortical μPo2decreased 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, CLcreawas reduced to 50%. An additional group of rats (n = 5) received fluid resuscitation. In these animals, RBF was restored to baseline, CLcreaincreased 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 Po2measurement, proving the hypothesis of our study. These observations suggest the involvement of hypoxia in the pathogenesis of endotoxemia-induced ARF. Copyright

• View at Publisher
• View at Pubmed
• View at Scopus
• View at Web of Science