Satona Tanaka, MD, Toyofumi F

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Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung Satona Tanaka, MD, Toyofumi F. Chen-Yoshikawa, MD, PhD, Moto Kajiwara, PhD, Toshi Menju, MD, PhD, Keiji Ohata, MD, Mamoru Takahashi, MD, Takeshi Kondo, MD, Kyoko Hijiya, MD, Hideki Motoyama, MD, PhD, Akihiro Aoyama, MD, PhD, Satohiro Masuda, PhD, Hiroshi Date, MD, PhD The Annals of Thoracic Surgery Volume 102, Issue 5, Pages 1717-1724 (November 2016) DOI: 10.1016/j.athoracsur.2016.05.037 Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Lung mechanics and oxygenation after reperfusion. (A) Maximum airway pressure. (B) Mean airway pressure. (C) Dynamic compliance. (D) Arterial partial pressure of oxygen. All were improved in imatinib group. Bars and the error bars show mean and SE of mean; *p < 0.05; **p < 0.01. The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Histologic findings (hematoxylin-eosin stain ×100) and lung wet to dry weight (W/D) ratio. (A) Sham group. (B) Vehicle group. (C) Imatinib group. (D) W/D ratio. Perivascular edema and hemorrhage were attenuated with lower W/D in imatinib group. Bars and error bars show mean and SE of mean; *p < 0.05. The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Neutrophil infiltration detected by naphthol AS-D chloroacetate esterase stain (×400). (A) Sham group. (B) Vehicle group. (C) Imatinib group. (D) Average number of neutrophils per high-power field (HPF). Neutrophil infiltration (arrows in B and C) was significantly decreased in the imatinib group. Bars and error bars show mean and SE of mean; *p < 0.05. (V = vessel.) The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Level of cytokines and chemokine in lung tissue lysates. (A) Interleukin (IL)-1β. (B) CXCL1. (C) IL-10. IL-10 level was significantly higher in the imatinib group. Bars and error bars show mean and SE of mean; *p < 0.05. The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Western blot analysis of lung tissue lysates evaluating phosphorylation of CrkL and Src and vascular endothelial cadherin (VEC) expression. (A) pCrkL and CrkL. (B) pSrc and Src. (C) VEC and β-actin. Phosphorylation of both CrkL and Src in lung tissue was inhibited by imatinib administration. Imatinib maintained VEC expression. Bars and error bars show mean and SE of mean; *p < 0.05. The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Correlation of lung tissue concentration and plasma concentration of imatinib and comparison of lung tissue concentration between right and left lungs. (A) Correlation of plasma and right lung. (B) Correlation of plasma and left lung. Concentration of bilateral lungs showed strong correlation with plasma concentration. Left (damaged) lung concentration was significantly lower than that of right lung. The Annals of Thoracic Surgery 2016 102, 1717-1724DOI: (10.1016/j.athoracsur.2016.05.037) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions