The effect of a combination of inhaled nitric oxide and an endothelinA-receptor antagonist on hemodynamic dysfunction in experimental acute pulmonary thromboembolism.
Although either inhaled nitric oxide (NO) or endothelinA receptor antagonist has been tried in the treatment of various forms of pulmonary hypertension, the effects of combination therapy have not been reported. We evaluated the effects of inhaled NO alone or a combination of inhaled NO and ZD2574 (an endothelinA receptor antagonist) in an experimental canine acute pulmonary thromboembolism model. Forty parts per million of inhaled NO alone, or a combination of inhaled NO and 10 mg/kg of ZD2574 was administered 1 hour after embolization with an autologous blood clot. We compared the hemodynamic and gas exchange parameters between the two treatment groups. Two treatment regimens decreased mean pulmonary arterial pressure and pulmonary vascular resistance and attenuated decrease in cardiac output. Moreover, systemic arterial hypotension or worsening of hypoxemia did not occur in either of the treatment groups. In the combined group, more favorable hemodynamic outcomes were maintained than in the inhaled NO alone group. And hemodynamic deterioration shown after NO withdrawal was attenuated in the combined group. These findings suggest that when inhaled NO is concomitantly administered with an ETA receptor antagonist, more favorable hemodynamic outcomes can be expected during and after NO inhalation in acute pulmonary thromboembolism.
Lee
Ji-Hyun
JH
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, College of Medicine University of Ulsan, Seoul, Korea.
Kim
Sehyun
S
Park
Byung-Kyu
BK
Kim
Woo-Sung
WS
Kim
Dong-Soon
DS
Kim
Won-Dong
WD
Lee
Sang-Do
SD
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D001993:Bronchodilator Agents; D065128:Endothelin Receptor Antagonists; D011719:Pyrazines; D013449:Sulfonamides; C415840:ZD 2574; D009569:Nitric Oxide