title: The novel synthetic serine protease inhibitor CU-2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery after cardiac surgery in a canine model.
abstract: BACKGROUND
  Serine protease inhibitors such as aprotinin reduce perioperative blood loss and may improve postpump cardiac performance owing to their anti-inflammatory properties. After the "aprotinin era," we investigated the efficacy of the novel synthetic serine protease inhibitors CU-2010 with improved coagulatory and anti-inflammatory profile on blood loss and reperfusion injury in a canine model.
  
  
  METHODS
  Thirty-six dogs were divided into 6 groups: control, aprotinin (n = 8; Hammersmith scheme), and CU-2010 (0.5, 0.83, 1.25, and 1.66 mg/kg). All animals underwent 90 minutes of cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. End points were blood loss during the first 2 hours after application of protamine, as well as recovery of myocardial contractility (slope of the end-systolic pressure-volume relationship, coronary blood flow, and vascular reactivity.
  
  
  RESULTS
  CU-2010 dose-dependently reduced blood loss to a degree comparable with that of aprotinin at lower doses and even further improved at higher doses (control/aprotinin/CU-2010 in increasing doses: 142 +/- 13, 66 +/- 17, 95 +/- 16, 57 +/- 17, 46 +/- 3, and 13 +/- 4 mL; P < .05). Whereas aprotinin did not influence myocardial function, CU-2010 improved the recovery of end-systolic pressure-volume relationship (control 60 +/- 6 mg kg vs aprotinin 73 +/- 7 mg/kg vs CU-2010 1.66 mg/kg; 102% +/- 8%; P < .05). Coronary blood flow (52 +/- 4 vs 88 +/- 7 vs 96 +/- 7; P < .05) and response to acetylcholine (44% +/- 6% vs 77% +/- 7% vs 81% +/- 6%; P < .05) were improved by both aprotinin and CU-2010.
  
  
  CONCLUSIONS
  The novel serine protease inhibitor CU-2010 significantly reduced blood loss after cardiac surgery comparable with aprotinin. Furthermore, an additionally improved anti-inflammatory profile led to a significantly improved postischemic recovery of myocardial and endothelial function.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Gabor.Szabo@urz.uni-heidelberg.de
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
authors.forename: Humaira
authors.initials: H
authors.lastname: Haider
authors.forename: Nelli
authors.initials: N
authors.lastname: Krieger
authors.forename: Susanne
authors.initials: S
authors.lastname: Bährle
authors.forename: Silke
authors.initials: S
authors.lastname: Niklisch
authors.forename: Christiane
authors.initials: C
authors.lastname: Miesel-Gröschel
authors.forename: Andreas
authors.initials: A
authors.lastname: van de Locht
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
mesh_terms: D000818:Animals; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010455:Peptides / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*
chemical_list: C548237:CU-2010; D010455:Peptides; D015842:Serine Proteinase Inhibitors