Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep

Abstract

Calzavacca P, Evans RG, Bailey M, Lankadeva YR, Bellomo R, May CN. Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep. Am J Physiol Regul Integr Comp Physiol 308: R832-R839, 2015. First published March 11, 2015 doi:10.1152/ajpregu.00515.2014.-The role of renal cortical and medullary hypoxia in the development of acute kidney injury is controversial, partly due to a lack of techniques for the long-term measurement of intrarenal oxygenation and perfusion in conscious animals. We have, therefore, developed a methodology to chronically implant combination probes to chronically measure renal cortical and medullary tissue perfusion and oxygen tension (tPO2) in conscious sheep and evaluated their responsiveness and reliability. A transit-time flow probe and a vascular occluder were surgically implanted on the left renal artery. At the same operation, dual fiber-optic probes, comprising a fluorescence optode to measure tPO2 and a laser-Doppler probe to assess tissue perfusion, were inserted into the renal cortex and medulla. In recovered conscious sheep (n ϭ 8) breathing room air, mean 24-h cortical and medullary tPO 2 were similar (31.4 Ϯ 0.6 and 29.7 Ϯ 0.7 mmHg, respectively). In the renal cortex and medulla, a 20% reduction in renal blood flow (RBF) decreased perfusion (14.6 Ϯ 8.6 and 41.2 Ϯ 8.5%, respectively) and oxygenation (48.1 Ϯ 8.5 and 72.4 Ϯ 8.5%, respectively), with greater decreases during a 50% reduction in RBF. At autopsy, minimal fibrosis was observed around the probes. In summary, we have developed a technique to chronically implant fiber-optic probes in the renal cortex and medulla for recording tissue perfusion and oxygenation over many days. In normal resting conscious sheep, cortical and medullary tPO 2 were similar. The responses to and recovery from renal artery occlusion, together with the consistent measurements over a 24-h period, demonstrate the responsiveness and stability of the probes. renal blood flow; kidney oxygenation; renal artery occlusion; perfusion; tissue oxygen tension.THE ETIOLOGY OF RENAL FAILURE is highly dependent on the setting in which it occurs. Nevertheless, considerable interest has focused on the potential for renal tissue hypoxia to provide a common pathway in multiple forms of acute and chronic kidney disease (18). Oxygen supply to the kidney via the renal artery far exceeds the kidney's metabolic requirements, yet the renal medulla, in particular, appears susceptible to the development of hypoxia (8).Many studies in which medullary tissue PO 2 (tPO 2 ) has been measured by polarographic electrodes in experimental animals and humans, breathing air or gas mixtures enriched in oxygen, have provided values of 10 -20 mmHg (4,8,9,11,25), close to the critical tPO 2 for isolated tubular cells (5 to 15 mmHg) (2, 3, 13, 14). These observations have led to the concept that the medulla normally operates on the brink of hypoxia and so is highly susceptible to factors that might reduce oxygen delivery or increase oxygen...

Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep

“…The probes are precalibrated by the manufacturer. We have recently shown that the values of LDF and tPO2 generated by these probes in the cortex and medulla of awake sheep are stable over many days and respond rapidly and reproducibly to changes in renal perfusion pressure (3). Provided the probes are not damaged during the experiment, values of PO2 obtained in saline solution saturated with CO2 (ϳ0 mmHg) or room air (ϳ160 mmHg) are similar before and after implantation.…”

“…At the same operation, two custom-built fiber-optic probes (CP-004-001; Oxford Optronix, Oxford, UK), with 20 mm of optical fiber extending from the outer sheath, were inserted in the kidney, as previously described (3). In brief, the outer sheath of the probes was glued to a plastic sheet, which was secured to the kidney capsule with cyanoacrylate adhesive.…”

“…The positions of the probes were confirmed at postmortem. Each probe contained a dual-fiber laser Doppler probe [for estimation of tissue perfusion by measurement of laser Doppler flux (LDF)], a single-fiber fluorescence optode (for measurement of tPO 2), and a thermocouple (for measurement of tissue temperature) (3,20,24). The probes are precalibrated by the manufacturer.…”

“…However, these techniques require the use of anesthesia and acute surgical exposure of the kidney. We have recently developed a method that allows direct measurement of regional tPO 2 , together with tissue laser Doppler flux as an index of perfusion, in awake sheep (3). This has the great advantage that it removes the confounding effects of anesthesia, which alters systemic hemodynamics and is likely to also alter intrarenal hemodynamics and tPO 2 .…”

Circadian Rhythm in Kidney Tissue Oxygenation in the Rat

“…This corroborates the hypothesis that oxygen delivery is the most important determinant of this circadian pattern in oxygenation. Recently, 24-h oxygen recordings in the kidneys have been obtained in sheep (Calzavacca et al, 2015). In that study, a clear 24-h pattern in tissue oxygenation of the kidneys was absent.…”