Protective Effect of Surfactant Inhalation against Warm Ischemic Injury in an Isolated Rat Lung Ventilation Model

Akihiro Ohsumi,Daisuke Nakajima,Jin Sakamoto,Masashi Kobayashi,Toru Bando,Fengshi Chen,Hiroshi Date,Ferenc Gallyas

doi:10.1371/journal.pone.0072574

Abstract

Warm ischemia-reperfusion injury remains a crucial issue in transplantation following the cardiac death of donors. Previously, we showed that surfactant inhalation during warm ischemia mitigated ischemia-reperfusion injury. This study investigated the mechanisms of surfactant inhalation protection of the warm ischemic lung after reoxygenation with ventilation alone. In an isolated rat lung ventilation model, cardiac arrest was induced in the CTRL (control) and SURF (surfactant treatment) groups by ventricular fibrillation. Ventilation was restarted 110 min later; the lungs were flushed, and a heart and lung block was procured. In the SURF group, a natural bovine surfactant (Surfacten®) was inhaled for 3 min at the end of warm ischemia. In the Sham (no ischemia) group, lungs were flushed, procured, and ventilated in the same way. Afterwards, the lungs were ventilated with room air without reperfusion for 60 min. Surfactant inhalation significantly improved dynamic compliance and airway resistance. Moreover, surfactant inhalation significantly decreased inducible nitric oxide synthase and caspase-3 transcript levels, and increased those of Bcl-2 and surfactant protein-C. Immunohistochemically, lungs in the SURF group showed weaker staining for 8-hydroxy-2′-deoxyguanosine, inducible nitric oxide synthase, and apoptosis, and stronger staining for Bcl-2 and surfactant protein-C. Our results indicate that surfactant inhalation in the last phase of warm ischemia mitigated the injury resulting from reoxygenation after warm ischemia. The reduction in oxidative damage and the inhibition of apoptosis might contribute to the protection of the warm ischemic lungs.

Highlights

To deal with the shortage of donor organs in lung transplantation, donation after cardiac death (DCD) has been introduced worldwide as a potential strategy to increase the donor pool
We investigated whether surfactant inhalation in the last phase of warm ischemia could mitigate injury resulting from reoxygenation in an isolated rat lung ventilation model
We found that a reduction in oxidative stress and inhibition of apoptosis may contribute to maintaining the viability of alveolar type II cells, leading to the protection of warm ischemic lungs

Summary

Introduction

To deal with the shortage of donor organs in lung transplantation, donation after cardiac death (DCD) has been introduced worldwide as a potential strategy to increase the donor pool. Warm ischemia inevitably occurs in DCD donors after cardiac arrest and may cause ischemia-reperfusion (I-R) injury after transplantation. A pulmonary surfactant is primarily composed of phospholipids and surfactant proteins, and functions to reduce the surface tension in the alveoli through forming a monolayer at the air-lipid interface. This mechanism prevents alveolar collapse [11,12] and protects the lung. We found that prerecovery surfactant inhalation improved graft lung function, maintained adenine nucleotide levels, and prevented cytokine production, resulting in attenuation of warm I-R injury [16]. Surfactant inhalation could serve as a potential method to reduce the severity of I-R injury. Both reports demonstrated that various factors could have potentially induced I-R injury

Methods

Results

Conclusion