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Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

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Abstract

Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.

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Authors and Affiliations

  1. Departments of Internal Medicine, Medical School, Ioannina, Greece

    Georgios Kalambokis MD & Epameinondas V. Tsianos MD

  2. Departments of Gastroenterology, Medical School, Ioannina, Greece

    Michalis Economou MD & Jihad Al Bokharhii MD

  3. Departments of Nuclear Medicine, Medical School, Ioannina, Greece

    Andreas Fotopoulos MD

  4. Departments of Cardiology, Medical School, Ioannina, Greece

    Pappas Christos MD

  5. Departments of Radiology, Medical School, Ioannina, Greece

    Kosta Paraskevi MD & Papadimitriou Konstantinos MD

  6. Departments of Statistics, Medical School, Ioannina, Greece

    Afroditi Katsaraki MD

  7. Department of Internal Medicine, Medical School of Ioannina, 45110, Ioannina, Greece

    Epameinondas V. Tsianos MD

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  1. Georgios Kalambokis MD
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  2. Michalis Economou MD
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  3. Andreas Fotopoulos MD
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  4. Jihad Al Bokharhii MD
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  6. Kosta Paraskevi MD
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  7. Papadimitriou Konstantinos MD
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  8. Afroditi Katsaraki MD
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  9. Epameinondas V. Tsianos MD
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Correspondence to Epameinondas V. Tsianos MD.

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Kalambokis, G., Economou, M., Fotopoulos, A. et al. Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites. Dig Dis Sci 50, 1771–1777 (2005). https://doi.org/10.1007/s10620-005-2935-8

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  • DOI: https://doi.org/10.1007/s10620-005-2935-8

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