Local Maximum Oxygen Disappearance Rate Has Limited Utility As a Measure of Local Renal Tissue Oxygen Consumption Publisher Pubmed



Nematbakhsh M^{1, 2} ; Eppel GA¹ ; Goddard D^{1, 3} ; Oconnor PM⁴ ; Evans RG¹ Show Affiliations
Source: Journal of Pharmacological and Toxicological Methods Published:2010

Abstract

Introduction: Methods for measurement of local oxygen consumption (VO2) are required to allow development of treatments for kidney disease that target kidney oxygen dysregulation. In anaesthetized rabbits, we determined whether local oxygen disappearance rate (ODR) during complete renal ischaemia reflects tissue VO2 in the kidney and in hindlimb skeletal muscle (biceps femoris). Methods: Whole kidney VO2 was determined under conditions employed to alter oxygen consumption. The ureter was ligated to reduce VO2 (n=6) or the mitochondrial uncoupler 2,4-dinitrophenol was administered to increase VO2 (n=6). An additional 10 rabbits were studied which received neither treatment. Immediately following VO2 measurements, oxygen partial pressure (PO2) was measured, over the first 60s after abrupt cardiac arrest, using fluorescence optodes and in a subset of experiments (n=6), Clark electrodes. Parallel experiments were performed in hindlimb skeletal muscle (biceps femoris). Results: ODR in the renal cortex and medulla, and in biceps femoris, was linear during the first ~15s after cardiac arrest (r2≈0.98). Using fluorescence optodes, maximum ODR averaged across all 22 rabbits in which the kidney was studied was -0.75±0.09 and -0.60±0.06mm Hg/s respectively in the renal cortex and medulla. Maximum ODR averaged across all 10 rabbits in which the biceps femoris was studied was -0.30±0.06mm Hg/s. ODR increased at greater initial PO2 only in the renal cortex. ODR in neither the renal medulla nor biceps femoris varied with whole organ VO2, although renal cortical ODR normalized for initial PO2 was significantly correlated with whole organ VO2 (r2=0.19). Maximum ODR obtained by Clark electrode was approximately four-fold greater than that obtained by fluorescence optode. Discussion: Because ODR correlates poorly with whole organ VO2, it likely has limited utility as a measure of local VO2. © 2010 Elsevier Inc.