Deleterious effect of nitric oxide inhibition in chronic hepatopulmonary syndrome.

Abstract

On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting.

• Authors: John A Almeida, Stephen M Riordan, Jia Liu, Sumedha Galhenage, Robert Kim, David Bihari, Eva A Wegner, Gregory B Cranney, Paul S Thomas
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 19 Issue 4 Pg. 341-6 (Apr 2007) ISSN: 0954-691X [Print] England
• PMID: 17353701 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Nitric Oxide
• Lypressin
• Terlipressin
• Cyclic GMP
• Curcumin
• Methylene Blue

Topics

• Antihypertensive Agents (adverse effects, therapeutic use)
• Blood Pressure (drug effects)
• Chronic Disease
• Curcumin (adverse effects, therapeutic use)
• Cyclic GMP (antagonists & inhibitors)
• Echocardiography
• Female
• Hepatopulmonary Syndrome (diagnosis, drug therapy, physiopathology)
• Humans
• Lypressin (adverse effects, analogs & derivatives, therapeutic use)
• Methylene Blue (adverse effects, therapeutic use)
• Middle Aged
• Nitric Oxide (antagonists & inhibitors)
• Terlipressin
• Treatment Failure
• Vascular Resistance (drug effects)