Inhaled CO(2) vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?

BACKGROUND: Unilateral 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% CO(2) to the inspiratory gas (FiCO(2)) prevents the injury, but it is not clear whether lung protection is a direct effect of CO(2) inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO(2) vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space. METHODS: Healthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with V(T) 10 ml/kg (injury, n = 6); VCV plus 5% FiCO(2) (FiCO(2), n = 7); VCV with V(T) 6 ml/kg (low V(T), n = 6); VCV plus additional circuit dead space (instrumental V(D), 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 (V(TRIGHT/LEFT)), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (Perfusion(LEFT)). RESULTS: In the left ligated lung, injury was prevented only in the FiCO(2) 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 FiCO(2) and in the low V(T) groups, but the other measures of injury showed lower intensity only in the FiCO(2) group. V(TRIGHT/LEFT) was lower and Perfusion(LEFT) was higher in the FiCO(2) group compared to other groups. CONCLUSION: In a model of UPAL, inhaled CO(2) but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.