A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.

Abstract

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.

• Authors: Masaaki Harada, Takahiro Oto, Shinji Otani, Kentaroh Miyoshi, Masanori Okada, Norichika Iga, Hitoshi Nishikawa, Seiichiro Sugimoto, Masaomi Yamane, Shinichiro Miyoshi
• Journal: General thoracic and cardiovascular surgery (Gen Thorac Cardiovasc Surg) Vol. 63 Issue 12 Pg. 645-51 (Dec 2015) ISSN: 1863-6713 [Electronic] Japan
• PMID: 26346003 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-6
• Interleukin-8
• Protease Inhibitors
• Proteinase Inhibitory Proteins, Secretory
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cytokines (drug effects, immunology)
• Enzyme-Linked Immunosorbent Assay
• Interleukin-6 (immunology)
• Interleukin-8 (drug effects, immunology)
• Lung (drug effects, immunology)
• Lung Compliance (drug effects)
• Lung Injury (prevention & control)
• Lung Transplantation (methods)
• Protease Inhibitors (pharmacology, therapeutic use)
• Proteinase Inhibitory Proteins, Secretory (pharmacology, therapeutic use)
• Reperfusion Injury (prevention & control)
• Swine
• Tumor Necrosis Factor-alpha (drug effects, immunology)
• Vascular Resistance (drug effects)
• Warm Ischemia