title: Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs.
abstract: Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. We studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial beta-adrenergic blockade (propranolol, 0.15 mg/kg i.v.) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa (from 19.8 +/- 6.1 to 28.3 +/- 8.7 mmHg, P < 0.01) and calculated PVR (from 437 +/- 139 to 720 +/- 264 dyn.s.cm-5, P < 0.01), both of which decreased with 17 ppm NO. ALI decreased arterial PO2 and increased airway pressure, shunt, and dead space ventilation. Ppa (19.8 +/- 6.1 vs. 23.4 +/- 7.7 mmHg) and PVR (437 +/- 139 vs. 695 +/- 359 dyn.s.cm-5, P < 0.05) were greater during ALI than during hyperoxia. No inhalation had no measureable effect during ALI before or after beta-adrenergic blockade. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 micrograms) induced an immediate decrease in Ppa and PVR during ALI.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania 15261.
authors.forename: J A
authors.initials: JA
authors.lastname: Romand
authors.forename: M R
authors.initials: MR
authors.lastname: Pinsky
authors.forename: L
authors.initials: L
authors.lastname: Firestone
authors.forename: H A
authors.initials: HA
authors.lastname: Zar
authors.forename: J R
authors.initials: JR
authors.lastname: Lancaster
mesh_terms: D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002263:Carboxyhemoglobin / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006454:Hemoglobins / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012129:Respiratory Function Tests; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D006454:Hemoglobins; D009829:Oleic Acids; C008657:nitrosyl hemoglobin; D019301:Oleic Acid; D009569:Nitric Oxide; D002263:Carboxyhemoglobin; D005996:Nitroglycerin