Addition of 5% CO2to inspiratory gas prevents lung injury in an experimental model of pulmonary artery ligation

Ines Marongiu, Elena Spinelli, Eleonora Scotti, Alessandra Mazzucco, Yu Mei Wang, Leonardo Manesso, Giulia Colussi, Osvaldo Biancolilli, Michele Battistin, Thomas Langer, Francesca Roma, Gianluca Lopez, Caterina Lonati, Valentina Vaira, Lorenzo Rosso, Stefano Ferrero, Stefano Gatti, Alberto Zanella, Antonio Pesenti, Tommaso Mauri

Research output: Contribution to journalArticlepeer-review


Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2. Objectives: This study aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlledmechanical ventilation and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiologicalmechanisms. Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation1FICO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with VT 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FIO2 50% (6FICO2 5%) for 48 hours or until development of severe lung injury. Measurements and Main Results: Histological, physiological, and quantitative computed tomography 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 compared with the ligation1FICO2 5% group. In the ligation group, the right lung received a larger fraction of VT and inflammation was more represented, whereas 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 antiinflammatory effects.

Original languageEnglish
Pages (from-to)933-942
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number8
Publication statusPublished - Oct 15 2021


  • COinhalation
  • Pulmonary perfusion
  • Therapeutic hypercapnia
  • VILI

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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