Protection against pulmonary O2 toxicity by N-acetylcysteine

Abstract

N-acetylcysteine (NAC) is a known antioxidant. We therefore investigated NAC as an agent protective against O2 toxicity in the lung. Twelve dogs were anaesthetized with sodium pentobarbital and ventilated with 100% O2 for 54 h. Five were given diluent and 7 intravenous NAC (loading dose prior to 100% O2 ventilation of 150 mg·kg-1 and maintenance dose of 20 mg·kg-1·h-1). Every 6 h, physiological evaluation of the pulmonary circulation, mechanical properties, and gas exchange was performed. Post-mortem evaluation consisted of gross examination and weighing followed by light and electron microscopy. By both functional and structural criteria, NAC protected against the effects of 100% O2. The NAC group developed significantly less increase in pulmonary vascular resistance, arterial carbon dioxide tension (PaCO2) and lung wet weight, while dynamic complicance was greater. NAC also delayed the development of abnormal ventilation-perfusion relationships and was associated with reduced pulmonary white cell accumulation, with less evidence of alveolar and interstitial oedema. NAC may well be worthy of evaluation as a therapeutic agent in human diseases characterized by oxidant damage.