title: Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung.
abstract: BACKGROUND
  Ischemia/reperfusion injury (IRI) remains a significant complication after lung transplantation. Endothelial damage and inflammation contribute to its development. Imatinib has been reported to regulate vascular permeability by maintaining endothelial junctions and showing antiinflammatory effects through inhibition of the Abl kinases. We hypothesized that imatinib could have a protective effect against IRI.
  
  
  METHODS
  Male Lewis rats were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes followed by reperfusion for 120 minutes. Imatinib mesylate (50 mg/kg) and a solvent were administered intraperitoneally 20 minutes before ischemia in the imatinib group and the vehicle group, respectively (n = 7 in each group). After reperfusion, lung function, lung wet to dry weight (W/D) ratio, and histologic findings were obtained. The expression of vascular endothelial cadherin (VEC), the phosphorylation level of CrkL (pCrkL) (an exclusive target of Abl kinases), and the cytokine level were evaluated using lung tissue lysate. The imatinib concentrations of plasma and lungs after reperfusion were measured in this hilar clamp model (n = 7).
  
  
  RESULTS
  In the imatinib group, lung function was improved with a lower W/D ratio. Perivascular edema and neutrophil infiltration were ameliorated. The imatinib group demonstrated maintained expression of VEC, inhibition of pCrkL, and a significantly higher level of interleukin (IL)-10. The imatinib concentration in both lungs showed a strong correlation with plasma concentration.
  
  
  CONCLUSIONS
  In a rat IRI model, imatinib attenuated lung injury by an antipermeability and antiinflammatory effect. The delivery and function of imatinib in the lung was also confirmed in this model.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Satona
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toyofumi F
authors.initials: TF
authors.lastname: Chen-Yoshikawa
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan; Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Moto
authors.initials: M
authors.lastname: Kajiwara
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Menju
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ohata
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hijiya
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Motoyama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: hdate@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D016207:Cytokines; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate