title: Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit.
abstract: Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.
authors.affiliation: Department of Pediatrics, Stanford University Medical Center, California 94305-5117, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Bradford
authors.forename: B
authors.initials: B
authors.lastname: Deb
authors.forename: R G
authors.initials: RG
authors.lastname: Pearl
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester