HEMODYNAMIC-EFFECTS AND METABOLIC-FATE OF INHALED NITRIC-OXIDE IN HYPOXIC PIGLETS

We describe the hemodynamic effects and metabolic fate of inhaled NO g as in 12 anesthetized piglets. Pulmonary and systemic hemodynamic resp onses to incremental NO (5-80 ppm) were tested during ventilation wi th high- 0.30 inspired O-2 fraction (FIO2) and low-O-2 (0.10 FIO2) m ixtures. In six animals, inhalation of 40 ppm NO was maintained over 6 h to test effects of prolonged exposure (0.30 FIO2). In the other six animals, pulmonary hypertension was induced by hypoxic ventilation (0 .10 FIO2) and responses to NO were tested. Inhaled low NO partially reversed pulmonary hypertension induced by alveolar hypoxia; mean pulm onary arterial pressure decreased from 31.4 +/- 2.3 mmHg during hypoxi a to 18.2 +/- 1.2 mmHg during 5 ppm NO. Mean pulmonary arterial pressu re at 0.10 FIO2 did not fall further at higher NO (10-40 ppm) and ne ver reached control levels. Pulmonary vascular resistance increased wi th institution of hypoxic ventilation and fell with subsequent adminis tration of NO, ultimately reaching control levels. Inhaled NO did not affect systemic vascular resistance. Plasma levels of NO2- + NO3- and methemoglobin (MetHb) levels increased with increasing NO. Over 6 h of NO administration during high-O-2 ventilation, MetHb equilibrated a t subtoxic levels while NO2- + NO3- increased. Nitrosylhemoglobin, ana lyzed by electron paramagnetic resonance spectrophotometry, was not de tected in blood at any time. At the relatively low concentrations (5-8 0 ppm) that are effective in relieving experimental pulmonary hyperten sion induced by alveolar hypoxia, inhaled NO gas causes accumulation o f NO2- + NO3- in plasma and a small increase in MetHb but no detectabl e nitrosylhemoglobin.