title: Long-term function and morphology of intestinal autografts and allografts in outbred dogs.
abstract: Although small bowel transplantation (SBTx) has become a clinical option, there have been few studies of long-term function and histopathology of intestinal grafts. Unrelated mongrel dogs received autologous (n = 4) or allogeneic (n = 11) orthotopic SBTx under oral cyclosporine. Intestinal graft function and routine/immunohistopathology of full-thickness intestine were studied. Six allograft and all isograft recipients had comparable body weight gain and are currently alive (> 420 days). Five allograft recipients were sacrificed because of significant body weight loss and malnutrition at a median of 119 days. Analyses of intestinal function in long-surviving recipients revealed marginal reduction of D-xylose/cyclosporine absorption, intestinal transit time, in vitro muscle contractility, and mucosal enzyme activity compared with normal dogs. However, these changes were insignificant and no statistical difference was seen between auto and long-surviving allografts. In histopathological analysis, long-surviving allografts had normal mucosa with submucosal, muscularis propria, and perineural (Auerbach's plexus) inflammation. Five allorecipients with malnutrition had mucosal atrophy/erosion and significantly reduced intestinal absorption and motility. Thus, denervated intestinal allografts are able to efficiently digest and absorb nutrients to support life. Results also indicate that these allografts experienced low-grade chronic rejection as evidenced in the submucosa and muscle layers, despite the lack of clinical symptoms.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Iwanami
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalesnik
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Okuda
authors.forename: Joao Seda
authors.initials: JS
authors.lastname: Neto
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Moore
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
mesh_terms: D000818:Animals; D001835:Body Weight; D016572:Cyclosporine / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D005772:Gastrointestinal Transit; D006085:Graft Survival / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D013997:Time Factors; D014182:Transplantation, Autologous / Q000473:pathology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology*; D014994:Xylose / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014994:Xylose