GF Xie, FF Xu, XM Shao, SZ Fan, B Sun

Selective pulmonary vasodilatation of inhaled nitric oxide is being tested extensively for persistent pulmonary hypertension of the newborn. We evaluated safety aspects of inhaled NO settings in ventilated rabbits. New Zealand White rabbits (2.5-3.0 kg) were anaesthetized, tracheotomized and mechanically ventilated with a pressure control mode and a tidal volume of 10-12 ml/kg for 8 hours. The animals were randomly allocated to three groups that received either: 21% (group 1), 60% (group 2) or 13% oxygen (group 3). NO (800 ppm) was added to the inspiratory limb of the ventilator circuit 25 cm proximal to the endotracheal tubing. Concentrations of NO and NO₂ were regulated with a mass flow controller, monitored with a NOxBOX NO/NO₂ analyser. The animals of group 1 and group 2 were exposed to 60 ppm NO throughout the experiments; group 3 were exposed to 10, 20, 40 and 80 ppm NO each for 30 mm followed by 10 and 5 ppm NO each for 3 hours. The variation in the concentration of inhaled NO was within ± 2 ppm. None of the animals that received NO₂ exceeded 2.6 ppm and none had methaemo- globin over 1%. There was a 1-2-fold increment of blood nitrite/nitrate level and five times more nitrite/nitrate in the urine of all the animals. No substantial changes of blood gas values, surfactant phospholipids, lung water content, dynamic lung compliance or lung morphology which would indicate deterioration due to inhaled NO were observed, except for group 3 in which a tendency towards decreased compliance and a low blood partial oxygen tension remained. Thus, under current settings, inhaled NO in ventilated rabbits in normoxic or hyperoxic conditions does not elicit adverse effects. (Partially supported by Nestle, Germany, China Medical Board of New York and Shanghai Education Foundation to B.S.)