title: In vitro effects of proteases in human pancreatic juice on stability of liquid and carrier-bound fibrin sealants.
abstract: BACKGROUND
  Fibrin sealants are used in pancreatic surgery to prevent leakage of pancreatic fluid and reduce associated complications. The efficacy of this approach is unclear.
  
  
  METHODS
  Fibrin clots were generated in vitro from two commercially available liquid fibrin sealants (Tissucol Duo® and Evicel®) and the carrier-bound fibrin sealant Tachosil®, and exposed to normal saline or human pancreatic fluid. Stability of the sealants was assessed by release of the fibrin and collagen degradation products, D-dimer and hydroxyproline. The effect of protease inhibitors on sealant breakdown was assessed.
  
  
  RESULTS
  Clots generated from liquid fibrin sealants degraded rapidly in pancreatic fluid, but not in normal saline. D-dimer release from fibrin clots by pancreatic fluid was approximately 1700 µg/ml after 24 h and less than 20 µg/ml by saline. Pancreatic fluid, but not normal saline, degraded both the fibrin and collagen component of Tachosil®. After 6 h, mean(s.e.m.) D-dimer levels in pancreatic fluid exposed to Tachosil® were 850(183) ng/ml, compared with 60(6) ng/ml in normal saline. The mean(s.e.m.) hydroxyproline concentration in pancreatic fluid was 497(17) µg/ml after a 24-h exposure to Tachosil®, compared with 26(12) µg/ml in normal saline. Protease inhibitors significantly inhibited breakdown of liquid sealants (D-dimer levels less than 50 µg/ml after 24 h) and Tachosil® (D-dimer release 179(12) ng/ml at 6 h; hydroxyproline release 181(29) µg/ml at 24 h).
  
  
  CONCLUSIONS
  Proteases in pancreatic juice effectively degrade both liquid and carrier-bound fibrin sealants in vitro. The use of these products in pancreatic surgery with the aim of preventing leakage of pancreatic fluid is not supported by this experimental study.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Adelmeijer
authors.forename: R J
authors.initials: RJ
authors.lastname: Porte
authors.forename: T
authors.initials: T
authors.lastname: Lisman
mesh_terms: D000704:Analysis of Variance; D001777:Blood Coagulation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004338:Drug Combinations; D004355:Drug Stability; D005337:Fibrin / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015718:Fibrin Tissue Adhesive / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D010189:Pancreatic Juice / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism
chemical_list: D004151:Dipeptides; D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; D015718:Fibrin Tissue Adhesive; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; C518955:TachoSil; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen; D010447:Peptide Hydrolases; D013917:Thrombin; D006909:Hydroxyproline