An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury

  • Yugeesh R. LankadevaEmail author
  • Junko Kosaka
  • Roger G. Evans
  • Clive N. May
Part of the Methods in Molecular Biology book series (MIMB, volume 1717)


The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe an ovine model of sepsis evoked by the administration of live Escherichia coli in which there is hypotension, peripheral vasodilatation with a large increase in cardiac output; a similar hyperdynamic state to that commonly reported in humans. Interestingly, in this sheep model of sepsis, despite an increase in global kidney blood flow, there is a progressive reduction in renal function. Although renal hyperperfusion develops, renal tissue hypoxia due to redistribution of intrarenal blood flow may contribute to the pathogenesis of septic AKI. We have, therefore, developed a novel methodology to chronically implant combination probes to monitor intrarenal tissue perfusion and oxygen tension during the development of septic AKI in conscious sheep with hyperdynamic sepsis.

Key words

Sepsis Hypotension Renal blood flow Cardiac output Acute kidney injury Ischemia Hypoxia 



This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC, 454615, 1009280, 1050672), and by funding from the Victorian Government Operational Infrastructure Support Grant. YRL was supported by a Postdoctoral Fellowship by the National Heart Foundation of Australia (NHF, 100869).


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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Yugeesh R. Lankadeva
    • 1
    Email author
  • Junko Kosaka
    • 1
  • Roger G. Evans
    • 2
  • Clive N. May
    • 1
  1. 1.Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  2. 2.Department of PhysiologyMonash UniversityParkvilleAustralia

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