Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Abstract

In vivo lung perfusion (IVLP) is an emergent strategy to treat lung metastases because it allows localized delivery of chemotherapy with minimal systemic exposure. Previously, short-term (± 30 minutes) IVLP resulted in variable efficacy and significant lung toxicity. We hypothesize that a modified IVLP strategy derived from an ex vivo lung perfusion technique could minimize lung injury. Our objective was to demonstrate the feasibility and safety of a modified prolonged (4 hours) IVLP. Six Yorkshire pigs were used for the experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary veins were cannulated, and the left lung was isolated in situ. IVLP was performed at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Göteburg, Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated and supplied with CO2 to physiologic levels before entering the lungs. A protective mode of ventilation was used. After IVLP, the left lung was allowed to reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary vascular resistance were used to assess left lung physiology. Histologic signs of lung injury were assessed before and after IVLP, and 4 hours after reperfusion. Lung function parameters were stable throughout the 4-hour IVLP and during reperfusion. No significant histologic evidence of acute lung injury was observed. Four hours of IVLP is feasible without adding significant lung injury. Prolonged perfusion time and a protective protocol might provide safer and more efficacious treatment of pulmonary metastases.