title: Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury.
abstract: Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation are unknown. To clarify this, we examined renal cortical, medullary, and urinary oxygenation in ovine septic acute kidney injury and the response to resuscitation with norepinephrine. A renal artery flow probe and fiberoptic probes were placed in the cortex and medulla of sheep to measure tissue perfusion and oxygenation. A probe in the bladder catheter measured urinary oxygenation. Sepsis was induced in conscious sheep by infusion of Escherichia coli for 32 hours. At 24 to 30 hours of sepsis, either norepinephrine, to restore mean arterial pressure to preseptic levels or vehicle-saline was infused (8 sheep per group). Septic acute kidney injury was characterized by a reduction in blood pressure of ∼12 mm Hg, renal hyperperfusion, and oliguria. Sepsis reduced medullary perfusion (from an average of 1289 to 628 blood perfusion units), medullary oxygenation (from 32 to 16 mm Hg), and urinary oxygenation (from 36 to 24 mm Hg). Restoring blood pressure with norepinephrine further reduced medullary perfusion to an average of 331 blood perfusion units, medullary oxygenation to 8 mm Hg and urinary oxygenation to 18 mm Hg. Cortical perfusion and oxygenation were preserved. Thus, renal medullary hypoxia caused by intrarenal blood flow redistribution may contribute to the development of septic acute kidney injury, and resuscitation of blood pressure with norepinephrine exacerbates medullary hypoxia. The parallel changes in medullary and urinary oxygenation suggest that urinary oxygenation may be a useful real-time biomarker for risk of acute kidney injury.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Yugeesh R
authors.initials: YR
authors.lastname: Lankadeva
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Junko
authors.initials: J
authors.lastname: Kosaka
authors.affiliation: Cardiovascular Disease Program, Bioscience Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
authors.affiliation: Faculty of Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
authors.affiliation: Department of Intensive Care and Department of Medicine, Austin Health, Heidelberg and The Australian and New Zealand Intensive Care Research Centre, Melbourne, Victoria, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: clive.may@florey.edu.au.
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced* / Q000150:complications; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000009:adverse effects* / Q000627:therapeutic use; D009846:Oliguria / Q000209:etiology; D010100:Oxygen / Q000032:analysis*; D010101:Oxygen Consumption; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012151:Resuscitation / Q000009:adverse effects; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D012756:Sheep; D014551:Urinary Tract / Q000378:metabolism* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D010100:Oxygen; D009638:Norepinephrine
keywords: cortical and medullary tissue oxygenation; cortical and medullary tissue perfusion; hypoxia; norepinephrine; renal blood flow; sepsis