Effects of propranolol on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat

Abstract

The effects of systemic and intraportal administration of propranolol on hepatic haemodynamics were studied in cirrhotic and non-cirrhotic rats. In the non-cirrhotic rat systemic infusion of 4 micrograms (kg body wt)-1 min-1 propranolol significantly decreased portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow without affecting heart rate. Similar changes were observed in the cirrhotic rat following an infusion of 2 micrograms (kg body wt)-1 min-1 propranolol. Higher rates of propranolol infusion produced greater reductions in portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow in cirrhotic and non-cirrhotic rats but these changes were accompanied by a bradycardia. The reduction in portal pressure effected by propranolol was accompanied by an increased splanchnic vascular resistance. Intraportal injection of propranolol resulted in a rapid but transient fall in portal pressure. The decrease in portal pressure was sustained if propranolol was infused intraportally. The results indicate that propranolol effects a reduction in portal pressure via a combination of increased splanchnic vascular resistance, increased hepatic arterial resistance and reduced cardiac output. The observation that propranolol can significantly reduce portal pressure without affecting heart rate may be clinically important in the long-term management of portal hypertension. Furthermore, the rapid reduction in portal pressure following intravenous administration suggests that propranolol may be of value in the acute control of variceal haemorrhage.

The effect of propranolol on the hyperaemic response of the hepatic artery to portal venous occlusion in the dog

“…Propranolol has recently been used as a means of decreasing PV pressure in order to reduce the risk of variceal bleeding in patients with portal hypertension (Lebrec et al, 1980;Bercoff et al, 1984;Ohnishi et al, 1985), though not with universal success (Burroughs et al, 1983;Anderberg et al, 1984). One mode of action is thought to be related to its vasoconstrictor action on the mesenteric vascular bed, caused by fl2-adrenoceptor blockade, which results in a fall in PV blood flow and pressure (Kroeger & Groszmann, 1985;Jenkins et al, 1985). However, in the current series of investigations PV (and HV) pressure remained unaltered despite a decrease in PV flow.…”

“…Propranolol can also produce a decrease in PV pressure by a reduction in PV flow as a result of a fall in cardiac output , due to fi-adrenoceptor blockade (Ohnishi et al, 1985). Most authors now conclude that propranolol achieves its reduction in PV flow and pressure through a combination of fl-adrenoceptor blockade (causing a reduction in cardiac output) and P2-adrenoceptor blockade (causing a reduction in mesenteric blood flow) Kroeger & Groszmann, 1985;Jenkins et al, 1985).…”

“…As these authors stated, 'the factors responsible for the discrepancy between man and dog are not known.' It is of interest that other authors have demonstrated a significant reduction in PV pressure with propranolol in cirrhotic rats (Jenkins et al, 1985), and it is therefore possible that differences between the dog and other species may be explained by the relative absence of potential portal-systemic collateral vessels in the canine circulation.…”

Long‐term effects of beta‐adrenergic blockade with nadolol on hepatic and renal haemodynamics and function in cirrhotics

“…After one month a significant correlation between the decrease in HVPG and that in CO was found (P<O.Ol), suggesting that the decrease in CO is an important determinant of the decrease in HVPG, induced through a reduction of portal blood inflow (Hillon et al, 1982;Jenkins et al, 1985). After six months of treatment the correlation was no longer significant, as reported in patients receiving the non-selective betablocker, propranolol (Hillon et al, 1982;Mills et al, 1984).…”

Reduction by Norepinephrine of the Side Effects Induced by Combined Hepatic Arterial Administration of Degradable Starch Microspheres and Adriamycin in Rats with a Liver Adenocarcinoma

“…In rabbits, hepatic tumor to normal tissue blood flow ratio was decreased by femoral intravenous norepinephrine, but it significantly increased, when intravenous propranolol was added (7). We therefore added propranolol to norepinephrine in one experiment and tried a dose level proposed for intraportal administration (8), as hepatic intraarterial doses were not found.…”