title: Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations.
abstract: Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.
authors.affiliation: Department of Physiology, University of Florida, Gainesville 32610, USA.
authors.forename: V
authors.initials: V
authors.lastname: DeMarco
authors.forename: J W
authors.initials: JW
authors.lastname: Skimming
authors.forename: T M
authors.initials: TM
authors.lastname: Ellis
authors.forename: S
authors.initials: S
authors.lastname: Cassin
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D000860:Hypoxia / Q000188:drug therapy; D009569:Nitric Oxide / Q000627:therapeutic use*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid