title: Further evidence for sustained systemic inflammation in xenograft recipients (SIXR).
abstract: BACKGROUND
  In pig-to-baboon heart/artery patch transplantation models, adequate costimulation blockade prevents a T-cell response. After heart transplantation, coagulation dysfunction (thrombocytopenia, reduced fibrinogen, increased D-dimer) and inflammation (increased C-reactive protein [CRP]) develop. We evaluated whether coagulation dysfunction and/or inflammation can be detected following pig artery patch transplantation.
  
  
  METHODS
  Baboons received heart (n = 8) or artery patch (n = 16) transplants from genetically engineered pigs and a costimulation blockade-based regimen. Heart grafts functioned for 15-130 days. Artery recipients were euthanized after 28-84 days. Platelet counts, fibrinogen, D-dimer, and CRP were measured.
  
  
  RESULTS
  Thrombocytopenia and reduced fibrinogen developed only in recipients of hearts not expressing a coagulation-regulatory protein (n = 4), but not in other heart or patch recipients. However, in heart recipients (n = 8), there were sustained increases in D-dimer (<0.5 to 1.9 ug/ml [P < 0.01]) and CRP (0.26-2.2 mg/dl [P < 0.01]). In recipients of artery patches, there were also sustained increases in D-dimer (<0.5 to 1.4 ug/ml [P < 0.01]) and CRP (0.26 to 1.5 mg/dl [P < 0.001]). An IL-6R antagonist suppressed the increase in CRP, but not D-dimer.
  
  
  CONCLUSIONS
  The pig artery patch model has proved valuable for determining immunosuppressive regimens that prevent sensitization to pig antigens. This model also provides information on the sustained systemic inflammation in xenograft recipients (SIXR). An IL-6R antagonist may help suppress this response.
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Hayato
authors: H
authors: Iwase
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Surgery Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy.
authors: Burcin
authors: B
authors: Ekser
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.|Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors: Huidong
authors: H
authors: Zhou
authors: Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
authors: Hong
authors: H
authors: Liu
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Vikas
authors: V
authors: Satyananda
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Rishab
authors: R
authors: Humar
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Pooja
authors: P
authors: Humar
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Hidetaka
authors: H
authors: Hara
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Cassandra
authors: C
authors: Long
authors: Department of Cardiac Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Jay K
authors: JK
authors: Bhama
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Pietro
authors: P
authors: Bajona
authors: Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors: Yi
authors: Y
authors: Wang
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Martin
authors: M
authors: Wijkstrom
authors: Revivicor, Blacksburg, VA, USA.
authors: David
authors: D
authors: Ayares
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Mohamed B
authors: MB
authors: Ezzelarab
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: David K C
authors: DK
authors: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000637:transplantation*; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D010215:Papio; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D013552:Swine; D014183:Transplantation, Heterologous
keywords: C-reactive protein; D-dimer; IL-6R blockade; baboons; coagulation; genetically engineered; inflammation; pigs; platelets; xenotransplantation