2. Academic Validation
  3. Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung

Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung

  • Ann Thorac Surg. 2016 Nov;102(5):1717-1724. doi: 10.1016/j.athoracsur.2016.05.037.
Satona Tanaka 1,  Toyofumi F Chen-Yoshikawa 1,  Moto Kajiwara 2,  Toshi Menju 1,  Keiji Ohata 1,  Mamoru Takahashi 1,  Takeshi Kondo 1,  Kyoko Hijiya 1,  Hideki Motoyama 1,  Akihiro Aoyama 1,  Satohiro Masuda 3,  Hiroshi Date 4
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 2 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.
  • 3 Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
  • 4 Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: hdate@kuhp.kyoto-u.ac.jp.
PMID: 27460916 DOI: 10.1016/j.athoracsur.2016.05.037
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.

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