Systemic and splanchnic hemodynamic effects of molsidomine in rats with carbon tetrachloride-induced cirrhosis.
Molsidomine, a long-acting vasodilator mainly used as an antianginal agent, was reported to decrease the portohepatic venous pressure gradient in patients with alcoholic cirrhosis. This study investigated the effects of linsidomine, the active metabolite of molsidomine, on systemic and splanchnic hemodynamics in rats with CCl4-induced cirrhosis using the microsphere technique. Compared with placebo-treated rats, linsidomine-treated animals were found to have a significant decrease in portal venous pressure (-18%, p less than 0.01) and in mean arterial pressure (-16%, p less than 0.01), smaller peripheral resistances (p less than 0.01), greater portal venous inflow (p less than 0.05), smaller splanchnic arteriolar resistances (p less than 0.01) and smaller protocol-lateral resistances (p less than 0.05). Cardiac output, hepatic arterial blood flow, portal blood flow and estimated hepatic blood flow were not significantly different between the two groups of animals. Linsidomine-treated rats exhibited a trend toward greater collateral blood flow compared with controls, but this difference was not significant. We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow. These effects should be beneficial for patients with cirrhosis and portal hypertension.
Desmorat
H
H
Service d'Hépato-Gastro-Entérologie-CHU Purpan, Toulouse, France.
Vinel
J P
JP
Lahlou
O
O
Pipy
B
B
Badia
P
P
Cales
P
P
Combis
J M
JM
Souqual
M C
MC
Pascal
J P
JP
D000818:Animals; D002251:Carbon Tetrachloride; D006439:Hemodynamics / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects*
D002251:Carbon Tetrachloride; D008981:Molsidomine