Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome.
Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) in both animals and humans with HPS has improved arterial hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 +/- 7 [SD] yr; alveolar-arterial oxygen gradient, range 19-76 mm Hg; arterial oxygen tension, range 37-89 mm Hg). Nebulized L-NAME maximally decreased exhaled NO (by -55%; P < .001), mixed venous nitrite/nitrate (by -12%; P = .02), and cardiac output (by -11%; P = .002) while increased systemic vascular resistance (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary vascular remodeling rather than to an ongoing vasodilator effect of enhanced NO production.
Gómez
Federico P
FP
Servei de Pneumologia, Hospital Clinic, Institut d'nvestigacions Biomidiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Barberà
Joan A
JA
Roca
Josep
J
Burgos
Felip
F
Gistau
Concepción
C
Rodríguez-Roisin
Robert
R
D000328:Adult; D000368:Aged; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D020065:Hepatopulmonary Syndrome / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009330:Nebulizers and Vaporizers; D011446:Prospective Studies
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester