LUNG OVEREXPANSION INCREASES PULMONARY MICROVASCULAR PROTEIN PERMEABILITY IN YOUNG LAMBS

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (Q̇(L)), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 ± 1 cmH2O and a VT of 10 ± 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 ± 3 cmH2O and a VT of 48 ± 4 ml/kg for 4-8 h. Q̇(L) increased from 2.1 ± 0.4 to 13.9 ± 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 ± 1 cmH2O and a VT of 23 ± 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 ± 1 cmH2O for 4-6 h without a change in VT. Q̇(L) decreased on average from 2.8 ± 0.6 to 1.9 ± 0.3 ml/h (P = 0.08), and L/P was unchanged. To determine whether the lymph and protein flow changes occur gradually as VT increases or abruptly at a threshold, we increased VT in a stepwise fashion in six lambs and observed no significant increase in Q̇(L) until maximal expansion (PIP 61 ± 3 cmH2O, VT 57 ± 3 ml/kg), at which point Q̇(L) increased to 11.5 ± 2.7 ml/h (base line 2.3 ± 0.5 ml/h) and L/P increased to 0.70 ± 0.01 (base line 0.64 ± 0.03). These findings suggest that overinflation, but not high PIP alone, increases net fluid filtration and protein flux in the newborn lung. This apparent change in pulmonary vascular permeability is a threshold phenomenon and may contribute to the lung edema that sometimes occurs after prolonged mechanical ventilation.