A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.
OBJECTIVE
Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP.


METHODS
EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage.


RESULTS
During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group.


CONCLUSIONS
A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. msa_hara@yahoo.co.jp.
Masaaki
M
Harada
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Takahiro
T
Oto
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Shinji
S
Otani
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Kentaroh
K
Miyoshi
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Masanori
M
Okada
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Norichika
N
Iga
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Hitoshi
H
Nishikawa
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Seiichiro
S
Sugimoto
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Masaomi
M
Yamane
Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Shinichiro
S
Miyoshi
D000818:Animals; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008170:Lung Compliance / Q000187:drug effects; D055370:Lung Injury / Q000517:prevention & control*; D016040:Lung Transplantation / Q000379:methods*; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology* / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology; D014655:Vascular Resistance / Q000187:drug effects*; D052096:Warm Ischemia
D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D011480:Protease Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D014409:Tumor Necrosis Factor-alpha
Ex vivo lung perfusion; Lung ischemia/reperfusion injury; Lung transplantation; Neutrophil elastase inhibitor