Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.
Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].
Frostell
C
C
Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston.
Fratacci
M D
MD
Wain
J C
JC
Jones
R
R
Zapol
W M
WM
D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000860:Hypoxia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology / Q000506:poisoning; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D014665:Vasodilator Agents; D009569:Nitric Oxide