Human ex vivo Lung Perfusion: A Pre-Clinical Model for Lung Disease

We report the first use of ex vivo lung perfusion (EVLP) in the genetic and physiologic modification of lungs from deceased pulmonary arterial hypertension (PAH) patients and propose this as a translational platform to both (1) derive clinically relevant mechanistic insights into pulmonary pathophysiology and (2) to test treatments on human lungs. The EVLP consist in the perfusion of the lungs out of the body during 6 hours. It is a well established protocol in where basically lungs are on a table connected to a close circuit containing a special perfusion solution that is circulated through the pulmonary vein and artery using a pump. The circuit contains also a deoxygenator. The perfusion temperature and flow are adjusted gradually and after 20 mins of perfusion the ventilation is initiated. Every hour lungs are recruited in order to assess pulmonary function and collect perfusate samples. In addition to perfusate, tissue samples from the lower lobe of the left lung and bronchial alveolar lavage (BAL) are collected at times T0, 3 and 6 hr. Two PAH donors (females; age 49 and 46 yr; with body mass index (BMI) 33.9 3.2 kg/m2) and two normal control donors (females; age 51 and 57 yr; BMI 28.5 1.6 kg/m2) were used for analysis. Gene expression profiling was also performed on tissue biopsies at several time points (T0, 3, and 6 hr).