Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation

Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2. Objectives: To characterize bilateral lung injury due to unilateral ligation of pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation. To investigate relevant pathophysiological mechanisms. Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (Ligation group), 7 to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (Ligation + FiCO2 5%), and 6 to no intervention (No Ligation). Then, all animals received mechanical ventilation with tidal volume (Vt) 10 ml/Kg, positive end-expiratory pressure 5 cmH2O, respiratory rate 25 bpm and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury. Measurements and main results: Histological, physiological and quantitative CT-scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the Ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics in comparison to the Ligation + FiCO2 5% group. In the Ligation group, the right lung received larger fraction of Vt, and inflammation was more represented, while CO2 dampened both processes. Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and anti-inflammatory effects. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).