title: Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation.
abstract: Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.
authors.affiliation: Division of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Unadkat
authors.forename: S
authors.initials: S
authors.lastname: Schneeberger
authors.forename: E H
authors.initials: EH
authors.lastname: Horibe
authors.forename: C
authors.initials: C
authors.lastname: Goldbach
authors.forename: M G
authors.initials: MG
authors.lastname: Solari
authors.forename: K M
authors.initials: KM
authors.lastname: Washington
authors.forename: V S
authors.initials: VS
authors.lastname: Gorantla
authors.forename: G M
authors.initials: GM
authors.lastname: Cooper
authors.forename: A W
authors.initials: AW
authors.lastname: Thomson
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D006614:Hindlimb / Q000637:transplantation*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013047:Specific Pathogen-Free Organisms; D014185:Transplantation, Isogeneic
chemical_list: D016572:Cyclosporine