title: Pattern of activin A and follistatin release in a sheep model of cardiopulmonary bypass.
abstract: OBJECTIVE
  Activin A, a member of transforming growth factor-β superfamily, has been established as a critical cytokine released early in endotoxemia and other inflammatory syndromes. The release of activin A and its binding protein, follistatin during cardiopulmonary bypass (CPB) has not been previously reported. Our study aimed to define the pattern of activin A and follistatin release in a sheep CPB model.
  
  
  METHODS
  Control group consisted of left thoractomy alone (n=6). CPB was performed using either unfractionated heparin (n=6) or lepirudin (n=6) as anticoagulant. Unlike heparin, lepirudin does not cause activin A and follistatin release on its own. Serum samples were assayed for activin A, follistatin, tumour necrosis factor-α and interleukin-6.
  
  
  RESULTS
  Compared with the control group, CPB using lepirudin was associated with a biphasic release of activin A. The first peak occurred within the first hour of CPB and a second peak occurred within the early post-operative period, coincident with a large release of follistatin. Close correlation was found between follistatin and IL-6 in the control and lepirudin groups, indicative of a role for follistatin in the acute phase response. In contrast to the control and lepirudin groups, CPB using heparin resulted in a concurrent release of activin A and follistatin.
  
  
  CONCLUSIONS
  CPB is a trigger for the release of biologically-active free activin A into the circulation, at levels considerably greater than that induced by surgery alone. Triggering release of this critical inflammatory cytokine suggests that activin A may contribute to the adverse outcomes associated with systemic inflammation in cardiac surgery.
authors.affiliation: Department of Surgery (Monash Medical Centre), Monash University, Victoria, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: David J
authors.initials: DJ
authors.lastname: Phillips
authors.forename: James
authors.initials: J
authors.lastname: McMillan
authors.forename: Penny
authors.initials: P
authors.lastname: Bedford
authors.forename: Jacob
authors.initials: J
authors.lastname: Goldstein
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hedger
authors.forename: Julian A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D016022:Case-Control Studies; D001026:Coronary Artery Bypass; D038681:Follistatin / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D023421:Models, Animal; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D038681:Follistatin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins