Lung Inflammation and Impairment of Hypoxic Pulmonary Vasoconstriction after High Tidal Volume Ventilation in Mice

Objective To investigate the effect of a prolonged period of high tidal volume [VT] ventilation on lung inflammation and hypoxic pulmonary vasoconstriction. Methods After tracheostomy and arterial line placement, anesthetized mice were divided to receive low tidal volume [VT] (n=10), (VT 8 ml/kg, PEEP 1.5 cmH2O, respiratory rate [RR] 100 b/min, FiO2 0.5), or high VT ventilation (n=10), (VT 29 ml/kg, PEEP 0 cmH2O, RR 90 b/min, FiO2 0.5). Static pressure-volume [PV] curve of the respiratory system was constructed every hour. After 10 hours, arterial blood gas analysis was performed, and extravacular lung water [EVLW] content was calculated. In additional mice (n=8, each group), after 6 hours, ventilation was changed to VT 7 ml/kg, PEEP 1.5 cmH2O, RR 100 b/min, FiO2 1, and left lung pulmonary vascular resistance [LPVR] was assessed before and during left mainstem bronchus occlusion [LMBO]. Results PV curve progressively shifted rightward and downward during high VT ventilation, while it did not change during low VT ventilation. After 10 hours of ventilation, PaO2 was lower in the high VT than in the low VT group (110±19 vs 214±8 mmHg, p<0.001), while there were no differences in PaCO2, pH, and Hb between the two groups. The EVLW was higher after high VT than after low VT ventilation (6.4±0.6 vs 3.5±0.3 g H2O/g dry lung, p<0.001). In the low VT group, LMBO increased LPVR (97±10%, p<0.001 vs pre-LMBO), while the ability of LMBO to increase LPVR was impaired after high VT ventilation (19±8%, p=NS vs pre-LMBO, p<0.01 vs low VT). Conclusions In anesthetized mice, prolonged high VT ventilation worsened respiratory mechanics, and systemic oxygenation. Impairment of HPV may contribute to hypoxemia after injurious ventilation.