Plasma Lipidomics Identify Pathways Linked to Acute Lung Injury in a Porcine One-Lung Ventilation Surgery Model

One-lung ventilation (OLV) is performed during lung surgeries by ventilating a single lung, while collapsing the operative lung to provide surgical exposure within the thoracic cavity. While a lung-protective ventilation strategy is recommended during OLV, increasing the fraction of inspired oxygen (FiO₂) or tidal volume (V_T) may be required to prevent hypoxemia during surgery. Unfortunately, these increases are associated with postoperative lung injury. Using a porcine model of OLV, our project aims to determine if high FiO₂ or V_T during OLV contributes to elevation of pro-inflammatory lipid mediators postoperatively. Fifteen three-month-old farm-bred pigs underwent left upper lobectomy requiring OLV. Pigs were exposed to one of three ventilation parameters: normoxic low V_T lung-protective ventilation LPV-NO, n = 5, FiO₂ < 50%, V_T = 6 mL/kg), hyperoxic lung-protective ventilation (LPV-HO, n = 5, FiO₂ >100%, V_T = 6 mL/kg), or normoxic high V_T (injurious mechanical ventilation) (IMV, n = 5, FiO₂ < 50%, V_T = 10-12 mL/kg). Arterial plasma was collected before and after OLV, and lipids were detected via LC-MS-MS. Lipidomic analysis demonstrated a statistically significant increase (FC = 2, p ≤ 0.05) in lysophosphatidylethanolamines (LPE 18:3, LPE 20:4, LPE 18:2, LPE 22:6), free fatty acids (FFA 20:4), phosphatidylserine (PS 38:5), lysophosphatidylcholine (LPC 18:1, LPC 18:3, LPC 22:6), triglyceride (TG 18:2-18:2-20:4), free fatty acids (FFA 20:5), linoleyl-carnitine molecules (C18-2 Linoleoyl Carnitine), and phosphatidylethanolamines (PE 36:5) in LPV-HO. IMV resulted in a significant increase (FC = 2, p ≤ 0.05) in triglyceride (TG 18:2-18:2-20:4), diglyceride (DG 18:1-20:4, DG 16:0-20:4), linoleyl-carnitine molecules (C18-2 Linoleoyl Carnitine), and free fatty acids (FFA 20:5). There was no significant change in lipid biomarker levels following LPV-NO post-surgery. Our lipidomic analysis supports that both high FiO₂ and V_T contribute to systemic lipid metabolic derangements. Lipids that were elevated in LPV-HO and IMV are associated with multiple inflammatory pathways implicated in lung injury. This suggests that intra-operative anti-inflammatory therapies targeted to these lipid pathways may reduce or prevent postoperative pulmonary complications after lung surgery.