Kyle Chin1, Melina P Cazorla-Bak1,2, Elaine Liu1, Linda Nghiem3, Yanling Zhang3, Julie Yu4, David F Wilson5, Sergei A Vinogradov5, Richard E Gilbert3,6, Kim A Connelly2,3,7, Roger G Evans8, Andrew J Baker1,3,9, C David Mazer1,2,9, Gregory M T Hare10,11,12. 1. Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. 2. Department of Physiology, University of Toronto, Toronto, ON, Canada. 3. Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 4. Deaprtment of Anesthesia and Perioperative Medicine, Western University, London, ON, Canada. 5. Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 6. Division of Endocrinology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 7. Division of Cardiology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 8. Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia. 9. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 10. Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. greg.hare@unityhealth.to. 11. Department of Physiology, University of Toronto, Toronto, ON, Canada. greg.hare@unityhealth.to. 12. Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. greg.hare@unityhealth.to.
Abstract
PURPOSE: The kidney plays a central physiologic role as an oxygen sensor. Nevertheless, the direct mechanism by which this occurs is incompletely understood. We measured renal microvascular partial pressure of oxygen (PkO2) to determine the impact of clinically relevant conditions that acutely change PkO2 including hyperoxia and hemodilution. METHODS: We utilized two-wavelength excitation (red and blue spectrum) of the intravascular phosphorescent oxygen sensitive probe Oxyphor PdG4 to measure renal tissue PO2 in anesthetized rats (2% isoflurane, n = 6) under two conditions of altered arterial blood oxygen content (CaO2): 1) hyperoxia (fractional inspired oxygen 21%, 30%, and 50%) and 2) acute hemodilutional anemia (baseline, 25% and 50% acute hemodilution). The mean arterial blood pressure (MAP), rectal temperature, arterial blood gases (ABGs), and chemistry (radiometer) were measured under each condition. Blue and red light enabled measurement of PkO2 in the superficial renal cortex and deeper cortical and medullary tissue, respectively. RESULTS: PkO2 was higher in the superficial renal cortex (~ 60 mmHg, blue light) relative to the deeper renal cortex and outer medulla (~ 45 mmHg, red light). Hyperoxia resulted in a proportional increase in PkO2 values while hemodilution decreased microvascular PkO2 in a linear manner in both superficial and deeper regions of the kidney. In both cases (blue and red light), PkO2 correlated with CaO2 but not with MAP. CONCLUSION: The observed linear relationship between CaO2 and PkO2 shows the biological function of the kidney as a quantitative sensor of anemic hypoxia and hyperoxia. A better understanding of the impact of changes in PkO2 may inform clinical practices to improve renal oxygen delivery and prevent acute kidney injury.
PURPOSE: The kidney plays a central physiologic role as an oxygen sensor. Nevertheless, the direct mechanism by which this occurs is incompletely understood. We measured renal microvascular partial pressure of oxygen (PkO2) to determine the impact of clinically relevant conditions that acutely change PkO2 including hyperoxia and hemodilution. METHODS: We utilized two-wavelength excitation (red and blue spectrum) of the intravascular phosphorescent oxygen sensitive probe Oxyphor PdG4 to measure renal tissue PO2 in anesthetized rats (2% isoflurane, n = 6) under two conditions of altered arterial blood oxygen content (CaO2): 1) hyperoxia (fractional inspired oxygen 21%, 30%, and 50%) and 2) acute hemodilutional anemia (baseline, 25% and 50% acute hemodilution). The mean arterial blood pressure (MAP), rectal temperature, arterial blood gases (ABGs), and chemistry (radiometer) were measured under each condition. Blue and red light enabled measurement of PkO2 in the superficial renal cortex and deeper cortical and medullary tissue, respectively. RESULTS: PkO2 was higher in the superficial renal cortex (~ 60 mmHg, blue light) relative to the deeper renal cortex and outer medulla (~ 45 mmHg, red light). Hyperoxia resulted in a proportional increase in PkO2 values while hemodilution decreased microvascular PkO2 in a linear manner in both superficial and deeper regions of the kidney. In both cases (blue and red light), PkO2 correlated with CaO2 but not with MAP. CONCLUSION: The observed linear relationship between CaO2 and PkO2 shows the biological function of the kidney as a quantitative sensor of anemic hypoxia and hyperoxia. A better understanding of the impact of changes in PkO2 may inform clinical practices to improve renal oxygen delivery and prevent acute kidney injury.
Authors: Jessica R Abrahamson; Austin Read; Kyle Chin; Nikhil Mistry; Hannah Joo; Jean-Francois Desjardins; Elaine Liu; Kerri Thai; David F Wilson; Sergei A Vinogradov; Jason T Maynes; Richard E Gilbert; Kim A Connelly; Andrew J Baker; C David Mazer; Gregory M T Hare Journal: Am J Physiol Regul Integr Comp Physiol Date: 2020-03-04 Impact factor: 3.619
Authors: Katharina Gerl; Karen A Nolan; Christian Karger; Michaela Fuchs; Roland H Wenger; Claus C Stolt; Carsten Willam; Armin Kurtz; Birgül Kurt Journal: Pflugers Arch Date: 2016-05-25 Impact factor: 3.657
Authors: Roger G Evans; Naoya Iguchi; Andrew D Cochrane; Bruno Marino; Sally G Hood; Rinaldo Bellomo; Peter R McCall; Clive N May; Yugeesh R Lankadeva Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-12-11 Impact factor: 3.619
Authors: Gregory M T Hare; Yanling Zhang; Kyle Chin; Kerri Thai; Evelyn Jacobs; Melina P Cazorla-Bak; Linda Nghiem; David F Wilson; Sergei A Vinogradov; Kim A Connelly; C David Mazer; Roger G Evans; Richard E Gilbert Journal: Physiol Rep Date: 2021-06