Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in an experimental pulmonary thromboembolism model.

Chaosheng Deng,Yuanhua Yang,Qichang Lin,Xiaoming Cao,Haibo Ding,Dawen Wu,Minxia Yang,Qiaoxian Zhang,Zhenguo Zhai,Chen Wang

doi:10.1007/s11239-015-1182-x

Abstract

Lung ischemia–reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. The inflammatory response mechanisms related to LIRI in pulmonary thromboembolism (PTE), especially in chronic PTE, need to be studied further. In a PTE model, inflammatory response and apoptosis may occur during LIRI and nitric oxide (NO) inhalation may alleviate the inflammatory response and apoptosis of pneumocytes during LIRI. A PTE canine model was established through blood clot embolism to the right lower lobar pulmonary artery. Two weeks later, we performed embolectomy with reperfusion to examine the LIRI changes among different groups. In particular, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), serum concentrations of tumor necrosis factor-α (TNF-α), myeloperoxidase concentrations in lung homogenates, alveolar polymorphonuclear neutrophils (PMNs), lobar lung wet to dry ratio (W/D ratio), apoptotic pneumocytes, and lung sample ultrastructure were assessed. The PaO2/FiO2 in the NO inhalation group increased significantly when compared with the reperfusion group 4 and 6 h after reperfusion (368.83 ± 55.29 vs. 287.90 ± 54.84 mmHg, P < 0.05 and 380.63 ± 56.83 vs. 292.83 ± 6 0.34 mmHg, P < 0.05, respectively). In the NO inhalation group, TNF-α concentrations and alveolar PMN infiltration were significantly decreased as compared with those of the reperfusion group, 6 h after reperfusion (7.28 ± 1.49 vs. 8.90 ± 1.43 pg/mL, P < 0.05 and [(19 ± 6)/10 high power field (HPF) vs. (31 ± 11)/10 HPF, P < 0.05, respectively]. The amount of apoptotic pneumocytes in the lower lobar lung was negatively correlated with the arterial blood PaO2/FiO2, presented a positive correlation trend with the W/D ratio of the lower lobar lung, and a positive correlation with alveolar PMN in the reperfusion group and NO inhalation group. NO provided at 20 ppm for 6 h significantly alleviated LIRI in the PTE model. Our data indicate that, during LIRI, an obvious inflammatory response and apoptosis occur in our PTE model and NO inhalation may be useful in treating LIRI by alleviating the inflammatory response and pneumocyte apoptosis. This potential application warrants further investigation.

Highlights

Pulmonary thromboembolism (PTE) is the third most common cause of death in hospitalized patients [1]
The inflammatory response mechanisms related to lung ischemia–reperfusion injury (LIRI) in pulmonary thromboembolism (PTE), especially in chronic PTE, need to be studied further
The inflammatory response mechanisms related to the LIRI in PTE, especially chronic PTE, are not studied as deeply as those involved in lung transplantation because there is no ideal PTE animal model due to the fact that animals do not develop spontaneous deep vein thrombosis or PTE

Summary

Introduction

Pulmonary thromboembolism (PTE) is the third most common cause of death in hospitalized patients [1]. The reperfusion pulmonary edema (RPE), which is one of the characteristics of LIRI, often develops within 48 h post-surgery such as thromboendarterectomy and lung transplant, thereby prolonging the intubation for mechanical ventilation, ventilator-associated infections, longer stays in the intensive care unit, and early postoperative mortality [6,7,8]. The inflammatory response plays a pivotal role in the development of LIRI after transplantation [9]. The inflammatory response mechanisms related to the LIRI in PTE, especially chronic PTE, are not studied as deeply as those involved in lung transplantation because there is no ideal PTE animal model due to the fact that animals do not develop spontaneous deep vein thrombosis or PTE

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Discussion

Conclusion