Influence of tidal volume on pulmonary NO release, tissue lipid peroxidation and surfactant phospholipids.

Mechanical stress during ventilation may cause or aggravate acute lung injury. This study investigates the influence of low vs. high tidal volume (V(t)) on factors known to play key roles in acute lung injury: nitric oxide release, eNOS and iNOS gene expression, lipid peroxidation (LPO), and surfactant phospholipids (PL). Isolated rabbit lungs were subjected to one of three ventilation patterns for 135 min (V(t)-PEEP): 6 ml/kg-0 cm H(2)O. 12 ml/kg-0 cm H(2)O 6 ml/kg-5 cm H(2)O, 12 ml/kg-0 cm H(2)O, and 6 ml/kg-5 cm H(2)O resulted in comparable peak inspiratory pressure (PIP). This allowed comparing low and high V(t) without dependence on PIP. Ventilatory patterns did not induce changes in pulmonary artery pressure, vascular permeability (K(f,c)), PIP or pulmonary compliance. High V(t) in comparison with both of the low V(t) groups caused an increase in BALF-nitrite (30.6+/-3.0* vs. 21.4+/-2.2 and 16.2+/-3.3 microM), BALF-PL (1110+/-19* vs. 750+/-68 and 634+/-82 microg/ml), and tissue LPO product accumulation (0.62+/-0.051* vs. 0.48+/-0.052 and 0.43+/-0.031 nmol/mg), *P<0.05 each. Perfusate nitrite and BALF-PL composition (assessed by use of 31P-NMR spectroscopy and MALDI-TOF mass spectrometry) did not differ among the groups. High V(t) ventilation reduced eNOS gene expression but did not affect iNOS expression. The increased release of NO and the accumulation of LPO products may represent early lung injury while elevated BALF-PL may reflect distension-induced surfactant secretion.