title: Aprotinin inhibits local platelet trapping and improves tissue destruction in hepatic cryosurgery.
abstract: BACKGROUND
  During the last decade, cryosurgery became an interesting alternative in the treatment of nonresectable liver neoplasms. The freeze-thaw procedure, however, may be associated with life-threatening thrombocytopenia due to local platelet trapping, and success of neoplasm ablation may be compromised by inadequate parenchymal cell destruction.
  
  
  METHODS
  Because aprotinin is capable of inhibiting the initiation of both coagulation and fibrinolysis, we studied-by whole body scintigraphy of Indium-111-labeled platelets and histomorphology in a porcine model of hepatic cryosurgery-whether this serine protease inhibitor is effective in attenuating platelet trapping and in improving tissue destruction.
  
  
  RESULTS
  Fifteen minutes of cryotherapy (-168 degrees C at the tip of the cryoprobe) induced a 30 +/- 4 cm(3) cryolesion, which presented with massive platelet trapping (14.0 +/- 1.7% cryolesion activity/whole body activity) and incomplete parenchymal cell destruction (0.9 +/- 0.3; score of hepatocyte nuclear destruction within the margin of the cryolesion). Aprotinin treatment with 500,000 IU initial bolus injection and additional 500,000 IU infusion over 3 hours did not affect the size of the cryolesion (29 +/- 3 cm(3)) but reduced local platelet activity (1.9 +/- 1.9%; P<.001) and induced hepatocyte nuclear destruction (3.0 +/- 0.0; P<.001).
  
  
  CONCLUSIONS
  Thus, our study indicates that aprotinin inhibits cryoablation-associated platelet trapping and improves tissue destruction. The serine protease inhibitor may represent a valuable adjunct in cryosurgery of hepatic neoplasms.
authors.affiliation: Department of General, Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Jens
authors.initials: J
authors.lastname: Czyborra
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Stefan
authors.initials: S
authors.lastname: Dietrich
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Carl M
authors.initials: CM
authors.lastname: Kirsch
authors.forename: Georg A
authors.initials: GA
authors.lastname: Pistorius
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D003452:Cryosurgery / Q000379:methods*; D005260:Female; D006801:Humans; D008099:Liver / Q000601:surgery; D008297:Male; D023421:Models, Animal; D010974:Platelet Aggregation / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013552:Swine
chemical_list: D015842:Serine Proteinase Inhibitors; D007611:Aprotinin