Surfactant Pretreatment Is Superior to Treatment after Reperfusion for Lung Ischemia-Reperfusion Injury

Abstract

Purpose Lung ischemia-reperfusion injury (LIRI) is a risk factor for development of primary graft dysfunction after lung transplantation. Treatment with surfactant ameliorates LIRI, but the optimal timing and surfactant dose are unknown. We compared the efficacy of surfactant treatment before ischemia with treatment at and 24 hours after reperfusion. Methods and Materials Male Sprague-Dawley rats (n=98) were randomized to receive intratracheally administered porcine surfactant in high (200 mg/kg) or low dose (50 mg/kg) either 1 hour before ischemia, at the start of reperfusion, or 24 hours after reperfusion. Sham-operated and untreated LIRI animals served as controls. LIRI was induced by clamping the bronchus, pulmonary artery and veins of the left lung for 150 minutes. After 72 hours, arterial oxygenation, pulmonary compliance, inflammatory cells in broncho-alveolar-lavage fluid and histological pulmonary injury were assessed. Results LIRI caused hypoxemia, impaired lung compliance, diffuse alveolar damage, inflammation consisting of granulocytes, macrophage and lymphocytes, and upregulation of MHCII+ on antigen presenting cells. Pretreatment with 200 mg/kg surfactant improved survival and lung function, averted fibroproliferation, and reduced diffuse alveolar damage and infiltration of T-cells in the ischemic lung. Surfactant treatment after reperfusion resulted in a mortality rate comparable to untreated LIRI and had no effect on pulmonary function, independent of the dose. Low dose surfactant reduced inflammation independent of the time of application, but the effect on lung function was less pronounced. Conclusions Pretreatment with high dose surfactant is superior to low dose treatment. Surfactant pretreatment is superior to treatment directly-, or 24 hours after reperfusion.