Haemodynamic effects of combined treatment with molsidomine and propranolol on portal hypertension in conscious and unrestrained cirrhotic rats.
We investigated the systemic and splanchnic haemodynamic effects of combined treatment with molsidomine and propranolol on cirrhotic rats. Liver cirrhosis was produced by repeated intraperitoneal injections of thioacetamide. The blood flow of each organ was measured serially using the radioactive microsphere method in the awake state before and after the administration of each agent. Cirrhotic rats received molsidomine (0-.5 mg/kg), propranolol (0.1 or 0.2 mg/min), both agents or placebo. Combination treatment with molsidomine and 0.1 mg/min propranolol significantly reduced portal pressure compared with molsidomine or propranolol alone (21 +/- 4 vs 15 +/- 3 or 11 +/- 2% P < 0.05). Systemic haemodynamic changes with this combined treatment were mild. This combined treatment slightly inhibited the molsidomine-induced decrease in portal vascular resistance (27 +/- 9 vs 31 +/- 6; NS) and markedly inhibited the molsidomine-induced decrease in splanchnic arterial resistance (7 +/- 6 vs 27 +/- 5% P < 0.05). Compared with low-dose propranolol administration, the combined treatment was associated with a significant decrease in portal vascular resistance (27 +/- 9% decrease vs 2 +/- 2% increase; P < 0.001) and a significant decrease in splanchnic arterial resistance (7 +/- 6% decrease vs 5 +/- 4% increase P < 0.05). The combination of molsidomine and high-dose propranolol (0.2 mg/min) caused a marked reduction in portal venous inflow, mean arterial pressure and cardiac index. We conclude that propranolol enhances the molsidomine-induced decrease in portal pressure by splanchnic vasoconstriction in association with a slight decrease in portal vascular resistance. The combination therapy with molsidomine and low-dose propranolol combination had more beneficial and less harmful effects on systemic and splanchnic haemodynamics and thus appears to be a superior method for treating portal hypertension.
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
N
N
Hori
T
T
Okanoue
Y
Y
Sawa
T
T
Mori
K
K
Kashima
D000818:Animals; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000627:therapeutic use*; D011433:Propranolol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D014665:Vasodilator Agents; D011433:Propranolol; D008981:Molsidomine