Effects of molsidomine, a long acting venous dilator, on portal hypertension. A hemodynamic study in patients with cirrhosis.
The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension.
Ruiz del Arbol
L
L
Hepatic Hemodynamics Laboratory, Hospital Clinic i Provincial, University of Barcelona, Spain.
García-Pagán
J C
JC
Feu
F
F
Pizcueta
M P
MP
Bosch
J
J
Rodés
J
J
D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006503:Hepatic Veins / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000494:pharmacology / Q000627:therapeutic use*; D013152:Splanchnic Circulation / Q000187:drug effects
D003692:Delayed-Action Preparations; D008981:Molsidomine