title: Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis.
abstract: BACKGROUND
  Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.
  
  
  METHODS
  Hyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis.
  
  
  RESULTS
  Hyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P < 0.001) and CO (P < 0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6.
  
  
  CONCLUSIONS
  In sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. p.calzavacca@gmail.com.|Department of Intensive Care and Department of Medicine, Austin Health, 145 Studley Road, Heidelberg, VIC, 3084, Australia. p.calzavacca@gmail.com.|Department of Anaesthesia and Intensive Care, AO Melegnano, PO Uboldo, Cernusco sul Naviglio, Italy. p.calzavacca@gmail.com.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calzavacca
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. yugeesh.lankadeve@monash.edu.|Department of Physiology, Monash University, Wellington Road, Clayton, VIC, 3800, Australia. yugeesh.lankadeve@monash.edu.
authors.forename: Yugeesh R
authors.initials: YR
authors.lastname: Lankadeva
authors.affiliation: Faculty of Veterinary Science, University of Melbourne, Corner Park Drive and Flemington Road, Melbourne, VIC, 3052, Australia. bais@unimelb.edu.au.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Wellington Road, Clayton, VIC, 3800, Australia. Michael.Bailey@monash.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Department of Intensive Care and Department of Medicine, Austin Health, 145 Studley Road, Heidelberg, VIC, 3084, Australia. Rinaldo.bellomo@austin.org.au.|The Australian and New Zealand Intensive Care Research Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia. Rinaldo.bellomo@austin.org.au.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. clive.may@florey.edu.au.
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D012756:Sheep; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D016207:Cytokines; D001262:Atenolol