Effect on dyspnoea and hypoxaemia of inhaled NG-nitro-L-arginine methyl ester in hepatopulmonary syndrome

Brussino, Luisa; Bucca, Caterina; Morello, Mara; Scappaticci, E; Mauro, Michele Di; Rolla, Giovanni

doi:10.1016/s0140-6736(03)13807-x

Cited by 99 publications

(48 citation statements)

References 5 publications

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“…3 However, we used a higher dose of L-NAME than that administered to a patient with HPS in a recent case report that successfully reduced exhaled NO and improved arterial oxygen tension. 15 Nevertheless, our results argue against an active functional effect of enhanced NO production on pulmonary circulation near the gas exchange zone, but not against the pathogenic role of NO, likely a key factor priming pulmonary vascular changes in HPS. 1 In fact, on the basis of the favorable hemodynamic effects of inhaled L-NAME, prolonged modulation of NO production could improve pathological changes and its functional consequences.…”

Section: Discussioncontrasting

confidence: 53%

“…10,13,14 In patients with HPS, there was a transient improvement in arterial oxygenation after intravenous methylene blue, an inhibitor of soluble guanylate cyclase and cyclic guanosine monophosphate production, a final molecular step for NO-mediated vasorelaxation. 13,14 Similarly, inhibition of NO synthase with nebulized N G -nitro-L-arginine methyl ester (L-NAME) in a patient with HPS improved arterial oxygen tension, 15 suggesting that the selective inhibition of pulmonary NO through the inhaled route could be of potential therapeutic benefit. Nevertheless, the precise role of a NO-dependent pulmonary vasodilatation involved in the pathogenesis of abnormal pulmonary gas exchange in HPS remains far from clear.…”

Section: See Editorial On Page 912mentioning

confidence: 99%

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

et al. 2006

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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. ( H epatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. 1 Arterial deoxygenation in HPS is caused by ventilation-perfusion mismatching and intrapulmonary shunt along with a diffusion-perfusion defect in most advanced cases. 2 Few experimental and clinical evidences in HPS suggest that enhanced pulmonary production of nitric oxide (NO) plays a key role in the development of intrapulmonary vascular dilatations. [3][4][5][6][7][8][9][10] Morphologically, the striking feature in HPS is widespread dilatation and increased number of pulmonary capillaries in alveolar regions 11 that suggest a vasculogenic rather than a vasoactive pathobiological process. 12 Studies with NO inhibitors in HPS, however, have highlighted that active NO-dependent pulmonary vasodilatation may contribute to the persistence of gas exchange abnormalities. 10,13,14 In patients with HPS, there was a transient improvement in arterial oxygenation after intravenous methylene blue, an inhibitor of soluble guanylate cyclase and cyclic guanosine monophosphate production, a final molecular step for NO-mediated vasorelaxation. 13,14 Similarly, inhibition of NO synthase with nebulized N G -nitro-L-arginine methyl ester (L-NAME) in a patient with HPS improved arterial oxygen tension, 15 suggesting that the selective inhibition of pulmonary NO through the inhaled route could be of potential therapeutic benefit. Nevertheless, the precise role of a NO-dependent pulmonary vasodilatation involved in the pathogenesis of abnormal pulmonary gas exchange in HPS remains far from clear.To shed further light into the pathogenesis of HPS and to explore the potential therapeutic a...

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Section: Discussioncontrasting

confidence: 53%

Section: See Editorial On Page 912mentioning

confidence: 99%

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

et al. 2006

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“…13 A case report using inhaled L-NAME, a specific nitric oxide synthase inhibitor, and a small case series using methylene blue, an inhibitor of cyclic guanosine monophosphate generation by guanylate cyclase showed short term improvement in oxygenation in HPS after acute administration. 14,15 These human studies support that pulmonary NO and cyclic guanosine monophosphate production contribute to changes in pulmonary vascular tone that influence oxygenation.…”

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confidence: 74%

Hepatopulmonary syndrome: More than just a matter of tone?

Fallon

2006

Hepatology

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“…Several studies have successfully used the following therapeutic approaches in patients with HPS: either intravenous introduction of methylene blue, which is the main inhibitor of NO molecular target, cyclic guanosine monophosphate or spraying with NO synthase inhibitor (N-nitro-L-arginine methyl ester) [31][32][33]. However, further studies showed, that NO concentration does not affect hyperdynamic circulation and the severity of liver damage in cirrhosis patients.…”

Section: Nitric Oxide Mediated Vasodilationmentioning

confidence: 99%