Interstitial lactate, inosine and hypoxanthine in rat kidney during normothermic ischaemia and recirculation

Abstract

The aim of this study was to determine the potential value of extracellular fluid (ECF) lactate, inosine and hypoxanthine for monitoring the disturbance in energy metabolism associated with kidney ischaemia and recirculation, using intrarenal microdialysis as sampling technique. Normothermic ischaemia was produced in rats by clamping of the left renal pedicle. Microdialysis probes were implanted into the renal cortex and the medulla, respectively. Dialysates were collected in 10-minute fractions before, during 20 (Group A) or 40 minutes (Group B) ischaemia and 2 hours of recirculation. Samples were analysed by HPLC for lactate, inosine and hypoxanthine. Ischaemia caused a dramatic increase of extracellular fluid lactate, inosine and hypoxanthine in both groups, reflecting the disturbance of energy metabolism. The basal extracellular fluid level of lactate as well as that during ischaemia was markedly higher in the medulla compared to cortex, whereas the relative change in lactate concentration was similar (i.e. about 4-fold). In group A all three metabolites returned to the pre-ischaemic level within 20 minutes after reperfusion. However, while inosine and hypoxanthine returned promptly to base line in Group B, recovery of lactate varied dramatically between animals suggesting a persistent metabolic disturbance in some rats. Our results indicate that extracellular fluid lactate, inosine and hypoxanthine, measured by intrarenal microdialysis, may be useful for monitoring of the energy state of the kidney during normothermic ischaemia and that extracellular fluid lactate may be a sensitive indicator of post-ischaemic disturbances in energy metabolism.