title: A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.
abstract: OBJECTIVE
  Haemorrhagic shock causes ischaemia and subsequent fluid resuscitation causes reperfusion injury, jointly resulting in high morbidity and mortality. We tested whether the anti-inflammatory fibrin-derived peptide, Bbeta(15-42), also called FX06, is tissue protective in a model of haemorrhagic shock.
  
  
  METHODS
  In a pig model, we standardised the severity of haemorrhagic shock by achieving a cumulative oxygen deficit of approximately 100ml/kg body weight by withdrawing blood over a period of 1h. This was followed by resuscitation with shed blood and full electrolyte solution, and pigs were monitored for 3 days. At reperfusion, 17 pigs were randomly assigned to FX06 or solvent treatment.
  
  
  RESULTS
  FX06-treated pigs demonstrated improved cardiac function (stroke volume index: 67ml/m(2) versus 33ml/m(2)), decreased troponin T release in the early reperfusion (0.24ng/ml versus 0.78ng/ml), decreased AST levels after 24h (106U/l versus 189U/l) and decreased creatinine levels after 24h (108micromol/l versus 159micromol/l). Furthermore, FX06-treated pigs demonstrated preservation of the gut/blood barrier, while controls demonstrated high endotoxin plasma levels indicating translocation of bacteria and/or its products (0.2EU/ml versus 24.3EU/ml) after 24h. This study also demonstrates a significantly improved neurological performance in the FX06 group as determined by S100beta serum levels (0.72microg/l versus 1.25microg/l) after 48h and neurological deficit scores (11 versus 70) after 24h.
  
  
  CONCLUSIONS
  FX06 - when administered as an adjunct to fluid resuscitation therapy - is organ protective in pigs. Further investigations are warranted to reveal the protective mechanism of FX06.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, University Hospital Rostock, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Roesner
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.forename: Thomas
authors.initials: T
authors.lastname: Iber
authors.forename: Christian
authors.initials: C
authors.lastname: Mutz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Gabriele E F
authors.initials: GE
authors.lastname: Nöldge-Schomburg
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000097:blood; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000097:blood; D007378:Interleukins / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood; D009460:Neurologic Examination; D010100:Oxygen / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D015424:Reperfusion / Q000379:methods*; D012151:Resuscitation; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D020107:Troponin T / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000925:Anticoagulants; D001786:Blood Glucose; D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D007378:Interleukins; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D020107:Troponin T; D014409:Tumor Necrosis Factor-alpha; C033786:fibrinogen Bbeta (15-42); D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D010100:Oxygen