EFFECTS OF INHALED NITRIC OXIDE ON THE ANESTHETIZED, MECHANICALLY VENTILATED, LARGE WHITE PIG

• Published in: Inhalation toxicology 2002-11, Vol.14 (11), p.1175-1185
• Main Authors: Ashley, Z., Jugg, B., Brown, R. F. R., Kenward, C. E., Platt, J., Rice, P., Harban, F. M. J.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Anesthesia, General; Animals; Capillaries - drug effects; Capillaries - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hemodynamics - drug effects; Nitric Oxide - administration & dosage; Nitric Oxide - toxicity; No-Observed-Adverse-Effect Level; Pulmonary Alveoli - blood supply; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - pathology; Respiration, Artificial; Swine; Vasodilator Agents - administration & dosage; Vasodilator Agents - toxicity
• ISSN: 0895-8378; 1091-7691
• DOI: 10.1080/08958370290084854

Inhalation of nitric oxide (NO) results in selective pulmonary vasodilation, which may be beneficial in the treatment of acute lung injury. However, NO has toxic effects, and it is important to monitor the effects and fate of inhaled NO. Under intravenous general anesthesia, large white female pigs were instrumented, ventilated with intermittent positive pressure ventilation (IPPV, FiO 2 0.3; TV 10 ml kg -1; RR 20 bpm; PEEP 3 cm H 2 O) and monitored for 24 h. Following a period of stabilization, groups were exposed to air (control), or to 10, 40, or 80 ppm NO, delivered via the endotracheal tube in each inspiratory breath. At regular intervals throughout the 24-h period, physiological measurements and arterial blood, plasma, and urine samples were collected. Inhalation of NO acted specifically on the pulmonary vasculature, as no alterations in systemic blood pressure were observed. Administration of NO at 80 ppm resulted in a decreased mean pulmonary artery pressure, decreased pulmonary wedge pressure, and increased methemoglobin and plasma/urine nitrate levels. At post mortem, congestion of the alveolar capillary network was noted in this group. In addition increases in plasma/urine nitrate levels were also observed in the 40 ppm group. In contrast, no significant alterations were observed in the 10 ppm group, compared to the control group. Therefore, 10 ppm inhaled NO is a dose that induced no pathological changes in normal healthy lungs and may be of use as a therapeutic adjunct in the management of acute lung injury.