title: Treatment with an antioxidant inhibits vascular changes caused by circulating lymphocytes during acute lung rejection in dogs.
abstract: BACKGROUND
  Experiments were designed to evaluate the effect of treatment with an inhibitor of lipid peroxidation, H 290/51, on the interaction of lymphocytes and pulmonary arteries during acute lung rejection. It was hypothesized that inhibition of lipid peroxidation would reduce contractions of the pulmonary arteries to autogenous rejection-activated lymphocytes.
  
  
  METHODS
  Single-lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days postoperatively; in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8; in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 was given orally for 3 days. The pulmonary arteries were removed, cut into rings, and suspended in organ chambers for measurement of isometric force.
  
  
  RESULTS
  Macrophage-depleted mononuclear cells (MNCs; lymphocytes) isolated from blood caused cell number-dependent contractions in rings of the pulmonary arteries from all dogs. In the rejecting dogs treated with H 290/51 (group 3), contractions to MNCs were significantly greater in rings without endothelium compared to rings with endothelium. Contractions to MNCs with or without endothelium were reduced by adding deteroxamine to the medium but not by adding superoxide dismutase and catalase.
  
  
  CONCLUSIONS
  The results of this study show that treatment with a lipid peroxidation inhibitor, H 290/51, does not prevent acute rejection of transplanted lungs. The treatment with the peroxidation inhibitor modifies contractions of the pulmonary arteries in response to rejection-activated lymphocytes, indicating that reactive oxidative metabolites may be involved in the vasoactive response resulting from this interaction.
authors.affiliation: Division of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
authors.forename: F
authors.initials: F
authors.lastname: Nilsson
authors.forename: H
authors.initials: H
authors.lastname: Scherstén
authors.forename: P O
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: H
authors.initials: H
authors.lastname: Tazelaar
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
authors.forename: C G
authors.initials: CG
authors.lastname: McGregor
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D007165:Immunosuppression Therapy / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D016040:Lung Transplantation / Q000276:immunology / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014184:Transplantation, Homologous
chemical_list: D000975:Antioxidants; C088233:H290-51; D007211:Indoles; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine