title: In the face of chronic aspiration, prolonged ischemic time exacerbates obliterative bronchiolitis in rat pulmonary allografts.
abstract: Aspiration of gastric fluid into the lung mediates the development of obliterative bronchiolitis (OB) in orthotopic WKY-to-F344 rat pulmonary transplants that have been subjected to immunosuppression with cyclosporine. However, the contribution of ischemic time to this process remains unknown. In this study, the effect of long (n = 16) and short (n = 12) ischemic times (average of 6 h and of 73 min, respectively) on rat lung transplants receiving aspiration of gastric fluid was assessed. Long ischemic times (LIT) led to significantly (p < 0.05) greater development of OB (ratio of OB lesions/total airways = 0.45 ± 0.07, mean ± standard error) compared to short ischemic times (ratio = 0.19 ± 0.05). However, the development of OB was dependent on aspiration, as controls receiving aspiration with normal saline showed little development of OB, regardless of ischemic time (p < 0.05). These data suggest that LIT, while insufficient by itself to lead to OB, works synergistically with aspiration of gastric fluid to exacerbate the development of OB.
authors.affiliation: Department of Surgery Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: J-C
authors.initials: JC
authors.lastname: Chang
authors.forename: J H
authors.initials: JH
authors.lastname: Leung
authors.forename: T
authors.initials: T
authors.lastname: Tang
authors.forename: M G
authors.initials: MG
authors.lastname: Hartwig
authors.forename: Z E
authors.initials: ZE
authors.lastname: Holzknecht
authors.forename: W
authors.initials: W
authors.lastname: Parker
authors.forename: R D
authors.initials: RD
authors.lastname: Davis
authors.forename: S S
authors.initials: SS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D002908:Chronic Disease; D050377:Cold Ischemia; D004195:Disease Models, Animal; D006084:Graft Rejection; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D053120:Respiratory Aspiration / Q000150:complications*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014184:Transplantation, Homologous; D052096:Warm Ischemia