Addition of 5% CO<sub>2</sub> to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation

Marongiu, Ines; Spinelli, Elena; Scotti, Eleonora; Mazzucco, A.; Wang, Yu Mei; Manesso, L.; Colussi, Giulia; Biancolilli, Osvaldo; Battistin, Michele; Länger, Thomas; Roma, Francesca; Lopez, Gianluca; Lonati, Caterina; Vaira, Valentina; Rosso, Lorenzo; Ferrero, Stefano; Gatti, Stefano; Zanella, Alberto; Artigas, Antonio; Mauri, Tommaso

doi:10.1164/rccm.202101-0122oc

Cited by 17 publications

(16 citation statements)

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“… Peltekova et al (2010) also demonstrated a similar decrease in MCP-1 and IL-6 in a mouse model of lung injury treated with hypercapnia ( Peltekova et al, 2010 ). A recent investigation in previously healthy pigs with unilateral ligation of the pulmonary artery ( Marongiu et al, 2021 ) found that inhaled CO 2 5% prevented an inflammatory reaction otherwise developing in both lungs. Of note, the driving pressures were significantly reduced in the iCO 2 5% group.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, the driving pressures were significantly reduced in the iCO 2 5% group. The alveolar and arterial CO 2 was double in the intervention group and ventilation-perfusion relationships (Va/Q) were not measured; it remains unclear whether the observed effects were predominately caused by the exogenous CO 2 or by a more favorable Va/Q allowing protective ventilation settings (hen-or-egg theorem) ( Marongiu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

et al. 2022

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Background and Objective: Lung-protective mechanical ventilation is known to attenuate ventilator-associated lung injury (VALI), but often at the expense of hypoventilation and hypercapnia. It remains unclear whether the main mechanism by which VALI is attenuated is a product of limiting mechanical forces to the lung during ventilation, or a direct biological effect of hypercapnia.Methods: Acute lung injury (ALI) was induced in 60 anesthetized rats by the instillation of 1.25 M HCl into the lungs via tracheostomy. Ten rats each were randomly assigned to one of six experimental groups and ventilated for 4 h with: 1) Conventional HighVENormocapnia (high VT, high minute ventilation, normocapnia), 2) Conventional Normocapnia (high VT, normocapnia), 3) Protective Normocapnia (VT 8 ml/kg, high RR), 4) Conventional iCO2Hypercapnia (high VT, low RR, inhaled CO2), 5) Protective iCO2Hypercapnia (VT 8 ml/kg, high RR, added CO2), 6) Protective endogenous Hypercapnia (VT 8 ml/kg, low RR). Blood gasses, broncho-alveolar lavage fluid (BALF), and tissue specimens were collected and analyzed for histologic and biologic lung injury assessment.Results: Mild ALI was achieved in all groups characterized by a decreased mean PaO2/FiO2 ratio from 428 to 242 mmHg (p < 0.05), and an increased mean elastance from 2.46 to 4.32 cmH2O/L (p < 0.0001). There were no differences in gas exchange among groups. Wet-to-dry ratios and formation of hyaline membranes were significantly lower in low VT groups compared to conventional tidal volumes. Hypercapnia reduced diffuse alveolar damage and IL-6 levels in the BALF, which was also true when CO2 was added to conventional VT. In low VT groups, hypercapnia did not induce any further protective effect except increasing pulmonary IL-10 in the BALF. No differences in lung injury were observed when hypercapnia was induced by adding CO2 or decreasing minute ventilation, although permissive hypercapnia decreased the pH significantly and decreased liver histologic injury.Conclusion: Our findings suggest that low tidal volume ventilation likely attenuates VALI by limiting mechanical damage to the lung, while hypercapnia attenuates VALI by limiting pro-inflammatory and biochemical mechanisms of injury. When combined, both lung-protective ventilation and hypercapnia have the potential to exert an synergistic effect for the prevention of VALI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

et al. 2022

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“…A previous study conducted by our group showed that the addition of 5% CO 2 to inspiratory gas prevents bilateral VILI in an experimental model of ligation of the left pulmonary artery ( 12 ). Mechanisms of protection included decreased inflammation in both lungs and more homogeneous distribution of ventilation, with reduced overdistension of the right lung.…”

Section: Introductionmentioning

confidence: 99%

Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?

et al. 2022

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BackgroundUnilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% CO2 to the inspiratory gas (FiCO2) prevents the injury, but it is not clear whether lung protection is a direct effect of CO2 inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO2vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space.MethodsHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VT 10 ml/kg (injury, n = 6); VCV plus 5% FiCO2 (FiCO2, n = 7); VCV with VT 6 ml/kg (low VT, n = 6); VCV plus additional circuit dead space (instrumental VD, n = 6). Histological score, regional compliance, wet-to-dry ratio, and inflammatory infiltrate were assessed to evaluate lung injury at the end of the study. To investigate the mechanisms of protection, we quantified the redistribution of ventilation to the non-ligated lung, as the ratio between the percentage of tidal volume to the right and to the left lung (VTRIGHT/LEFT), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (PerfusionLEFT).ResultsIn the left ligated lung, injury was prevented only in the FiCO2 group, as indicated by lower histological score, higher regional compliance, lower wet-to-dry ratio and lower density of inflammatory cells compared to other groups. For the right lung, the histological score was lower both in the FiCO2 and in the low VT groups, but the other measures of injury showed lower intensity only in the FiCO2 group. VTRIGHT/LEFT was lower and PerfusionLEFT was higher in the FiCO2 group compared to other groups.ConclusionIn a model of UPAL, inhaled CO2 but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.

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“…From the Authors, We thank Dr. Ajay Kumar Jha for the insightful comments on our recent experimental study [1]. Indeed, the experiment offers food for thoughts as we are at the very beginning of understanding pathophysiological changes induced by unilateral pulmonary artery ligation (UPAL) and mechanisms of lung protection by inhaled 5% CO 2 .…”

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Reply to Jha: Addition of 5% CO₂ to Inspiratory Gas in Preventing Lung Injury Due to Pulmonary Artery Ligation

Spinelli

Mauri

2022

Am J Respir Crit Care Med

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

Cited by 17 publications

References 38 publications

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?

Reply to Jha: Addition of 5% CO₂ to Inspiratory Gas in Preventing Lung Injury Due to Pulmonary Artery Ligation

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

Cited by 17 publications

References 38 publications

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury

Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?

Reply to Jha: Addition of 5% CO2 to Inspiratory Gas in Preventing Lung Injury Due to Pulmonary Artery Ligation

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

Reply to Jha: Addition of 5% CO₂ to Inspiratory Gas in Preventing Lung Injury Due to Pulmonary Artery Ligation