title: Effects of renal denervation on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.
abstract: OBJECTIVE
  To determine the influence of the renal sympathetic nerves on the pathogenesis of septic acute kidney injury.
  
  
  METHODS
  Interventional control study to determine the effects of renal denervation in ovine hyperdynamic sepsis.
  
  
  METHODS
  Research Institute.
  
  
  METHODS
  Twenty-four adult Merino ewes.
  
  
  METHODS
  The effects of infusion of angiotensin II and norepinephrine and induction of hyperdynamic sepsis by administration of live Escherichia coli were examined in control sheep and in sheep at 2 weeks after bilateral renal denervation (n = 10/group).
  
  
  RESULTS
  Systemic hemodynamics and renal function were measured in conscious sheep instrumented with flow probes on the pulmonary and renal arteries. Angiotensin II, but not norepinephrine, had a greater pressor effect in denervated animals. Sepsis increased cardiac output by 60%, renal blood flow by 35%, and arterial lactate by approximately four-fold. The denervated compared with the control group had a greater degree of hypotension during sepsis (68 vs 81 mm Hg; p = 0.003) and a reduction in the early polyuric response (from 496 to 160 mL at 2-8 hr of sepsis; p < 0.001). Creatinine clearance decreased similarly in both groups.
  
  
  CONCLUSIONS
  In experimental hyperdynamic sepsis, renal denervation was associated with greater hypotension and a loss of the initial diuresis, but no significant change in creatinine clearance. In sepsis, the renal nerves help support arterial pressure and determine the initial diuretic response, but septic acute kidney injury developed similarly in the innervated and denervated groups.
authors.affiliation: 1Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia. 2Department of Intensive Care, Austin Health, Heidelberg, VIC, Australia. 3Department of Anaesthesia and Intensive Care, AO Melegnano, PO Uboldo, Cernusco sul Naviglio, Italy. 4Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia. 5Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calzavacca
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Elena
authors.initials: E
authors.lastname: Velkoska
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramchandra
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000150:complications; D005260:Female; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D007668:Kidney / Q000098:blood supply / Q000294:innervation* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D000804:Angiotensin II; D003404:Creatinine; D009638:Norepinephrine