title: Effects of long-term administration of recombinant human protein C in xenografted primates.
abstract: BACKGROUND
  The role potential of recombinant human activated protein C (rhaPC), a recently developed molecule with anticoagulant and antiinflammatory properties, in prolonging survival in immunosuppressed primate recipients of porcine renal xenografts has been evaluated.
  
  
  METHODS
  rhaPC was administered daily for 5 days (24 μg/kg/hr; group A; n = 3) or throughout the postoperative period (8-24 μg/kg/hr; group B; n = 2; or 24-48 μg/kg/hr; group C; n = 4). Animals in group D (n = 2) received rhaPC daily (24 μg/kg/hr) combined with recombinant human antithrombin (84 U/kg every 8 hr). Two animals served as control (group E).
  
  
  RESULTS
  The results indicate that rhaPC is protective against fibrin deposition early after transplantation but does not prevent fibrin deposition and the occurrence of acute humoral xenograft rejection (AHXR) later on. Animals in the study survived between 8 and 55 days. At the dose used, rhaPC is able to prevent fibrin deposition in the graft in the first 2 weeks after xenotransplantation, except when it is administered in conjunction with antithrombin. However, rhaPC did not prevent the eventual occurrence of AHXR in primate recipients of porcine xenografts.
  
  
  CONCLUSIONS
  In this pig to primate model, rhaPC confers a short advantage in the prevention of early perioperative xenograft damage but does not represent an effective strategy for preventing AHXR.
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, 2nd Chair of Internal Medicine, University of Padua, Padua, Italy. paolo.simioni@unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Massimo
authors.initials: M
authors.lastname: Boldrin
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gavasso
authors.forename: Michela
authors.initials: M
authors.lastname: Seveso
authors.forename: Claudia
authors.initials: C
authors.lastname: Radu
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bulato
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Laura
authors.initials: L
authors.lastname: Cavicchioli
authors.forename: Diana
authors.initials: D
authors.lastname: Bertini
authors.forename: Giulia M
authors.initials: GM
authors.lastname: De Benedictis
authors.forename: Federica
authors.initials: F
authors.lastname: Besenzon
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldan
authors.forename: Luca
authors.initials: L
authors.lastname: Spiezia
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Ermanno
authors.initials: E
authors.lastname: Ancona
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000991:Antithrombins / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology; D008252:Macaca fascicularis; D011486:Protein C / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D034421:Sus scrofa; D014183:Transplantation, Heterologous
chemical_list: D000991:Antithrombins; D011486:Protein C; D011994:Recombinant Proteins; D005337:Fibrin; C421124:drotrecogin alfa activated