Effects of nebulized NG-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome

Authors

  • Federico P. Gómez,

    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
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  • Joan A. Barberà,

    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
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  • Josep Roca,

    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
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  • Felip Burgos,

    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
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  • Concepción Gistau,

    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
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  • Robert Rodríguez-Roisin

    Corresponding author
    1. Servei de Pneumologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
    • Servei de Pneumologia, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
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    • fax (34) 932275404

    • Robert Rodríguez-Roisin holds a career scientist award (2001-07) from the Generalitat de Catalunya.


  • See Editorial on Page 912

  • Potential conflict of interest: Nothing to report.

Abstract

Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with NG-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. (HEPATOLOGY 2006;43:1084–1091.)

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