The application of an open lung strategy after cardio-circulatory death in rats preserves lung viability and promotes the up-regulation of protective genes

Introduction: Lungs procured from non-heart-beating donors have been used to increase the number of available organs for transplantation. Objective: To investigate if the application of an open lung strategy (OLS) improves preservation after cardiac arrest (CA). Material and methods: Sprague–Dawley rats were subjected to CA and to a no-touch period of 1 h, then randomized to OLS (OLS, continuous positive airway pressure ventilation, n=5) or left untouched (RT, n=5) for 2 h. Lungs retrieved from heart-beating animals (HB, n=5) or immediately after asystolia (Flush, n=5) were considered as controls. Fifteen rats were used to evaluate wet-to-dry weight ratio (W/D), histology, cell viability (Trypan-blue dye), apoptosis (Tunel assay), and gene expression (RT-PCR with low-density arrays). Additional lungs (n=15) were subjected to ex-vivo perfusion for 15 min. Pulmonary artery pressure (PAP) was recorded. Perfusate was collected every 5 min for hemogasanalysis and hemoglobin assessment. Results: Although W/D and histological outcomes were similar between OLS and RT groups, cell viability was significantly improved by ventilation (p<0.05). Compared to heart-beating, OLS induced a number of protective genes, including anti-oxidative molecules, immediate early response genes, anti-inflammatory factors, and heat shock proteins (p<0.05). During ex-vivo perfusion, lungs of RT group showed augmented PAP relative to Flush (p=0.031), whereas OLS did not differ from controls (p=0.539). Finally, lactate (p=0.003 at 15 min) and hemoglobin (p=0.037) were higher in the RT perfusates compared to Flush. Conclusion: The application of an OLS after CA allowed prolonged lung preservation and exerted a beneficial effect.