Background: We recently reported that post-pneumonectomy pulmonary oedema (PPO) occurs after ventilating the remaining lung with excessive tidal volumes. Studies in small animals have indicated that nitric oxide (NO) release increases in hyper-inflated lungs, but confirmatory evidence from larger animals is still lacking. We hypothesized that PPO could be prevented by methylene blue (MB), an inhibitor of NO synthase.
Methods: Sheep were subjected to a right-sided pneumonectomy (PE) and randomly assigned to a protectively ventilated group ((PROTV group, n=7) with tidal volumes of 6 ml/kg at 20 inflations/min and a positive end-expiratory pressure (PEEP) of 2 cmH(2)O, and two groups undergoing 'injurious ventilation' (INJV) with tidal volumes of 12 ml/kg and zero end-expiratory pressure (ZEEP), a control group (INJV group, n=7) and a treatment group subjected to MB 1 h after PE (INJV+MB group, n=7). Haemodynamic variables, lung mechanics, blood gases and plasma nitrites and nitrates (NOx) were determined.
Results: PE reduced pulmonary blood volume, extravascular lung water (EVLWI) and quasistatic lung compliance in all groups, in parallel with a rise in peak airway pressure (P<0.05). In the INJV group, pulmonary arterial pressure, EVLWI and pulmonary vascular permeability index increased and arterial oxygenation decreased towards cessation of the experiments. These changes were not antagonized by MB. Plasma NOx increased in all the groups compared with baseline, but with no intergroup difference.
Conclusion: MB did not reduce PPO and accumulation of NOx in sheep subjected to ventilation with excessive tidal volumes and ZEEP.