Increased Blood Flow Through the Portal System in Cirrhotic Rats

Vorobioff, Julio; Bredfeldt, James E.; Groszmann, Roberto J.

doi:10.1016/s0016-5085(84)80072-4

Cited by 303 publications

(75 citation statements)

References 14 publications

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“…Nevertheless the increase in HBF associated to maintainance of HVPG strongly suggests a decrease in resistance, in agreement with results in experimental animals (Reichen & Le, 1986). However all mechanisms increasing cardiac output and splanchnic blood inflow also increase portal pressure in cirrhosis (Blendis, 1981;Vorobioff et al, 1984;McCormick & Hegarthy, 1986); therefore arterial vasodilation induced by verapamil in the arterial part of the splanchnic circulation probably hinders the effect of the drug on portohepatic resistance and maintains portal pressure at the same level.…”

Section: Discussionsupporting

confidence: 85%

The calcium‐channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

Merkel

Gatta

Bolognesi

et al. 1988

Brit J Clinical Pharma

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1. Recently the calcium‐channel blocker, verapamil, has been reported to decrease portal pressure in rats with experimental cirrhosis and in patients with liver cirrhosis. 2. In eight patients with alcoholic cirrhosis the effect of verapamil (5 mg i.v.) on systemic and splanchnic haemodynamics was investigated. 3. Mean arterial pressure, wedged hepatic venous pressure, hepatic venous pressure gradient, and verapamil plasma concentrations were measured before and at 10, 20, 30 min following 5 mg i.v. administration of verapamil. At 30‐40 min cardiac output, systemic vascular resistance and hepatic blood flow were also measured. 4. Verapamil plasma concentrations averaged 47.9 +/− 52.0, 36.5 +/− 36.3, 31.3 +/− 33.9 ng ml‐1 at 10, 20, 30 min respectively: mean arterial pressure and systemic vascular resistance decreased significantly (‐9% and −14% respectively), and cardiac index increased significantly (+8%). Wedged hepatic venous pressure and hepatic venous pressure gradient remained unchanged, variations never exceeding 0.2 kPa. Hepatic blood flow increased significantly by 12%. 5. These results show that i.v. administration of 5 mg verapamil does not decrease portal pressure in alcoholic cirrhosis. This lack of effect is probably the consequence of a balance between decrease in porto‐hepatic vascular resistance and increase in splanchnic blood inflow.

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Section: Discussionsupporting

confidence: 85%

The calcium‐channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

Merkel

Gatta

Bolognesi

et al. 1988

Brit J Clinical Pharma

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“…Cardiac output and regional blood flows were measured using a radioactive microsphere technique (15), as previously described (7,(9)(10)(11). A reference sample was obtained from the femoral artery catheter for 75 sec at a rate of 1 ml per min using a continuous withdrawal pump.…”

Section: Methodsmentioning

confidence: 99%

“…The radioactivity (cpm) of each organ was determined in a gammascintillation counter (Packard 800c). The interference of 51Cr radioactivity (energy window: 240 to 400 keV) into ""Ce channel (energy window: 100 to 165 keV) was corrected by using 51Cr and "' Ce standards (6,7,(9)(10)(11).…”

Section: Liver Radioactivity + Lung Radioactivitymentioning

confidence: 99%

“…Therefore, in this model, measured changes in portal vascular resistance (PVR) mainly reflect changes in the resistance of the collaterals (6). On the contrary, in intrahepatic models of portal hypertension, such as CC1,-induced cirrhosis, the formation of portosystemic collaterals is usually mild and is very variable (8)(9)(10). Therefore, in cirrhosis, measured changes in PVR reflect changes in the intrahepatic vascular resistance (9).…”

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confidence: 99%

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Propranolol Decreases Portal Pressure Without Changing Portocollateral Resistance in Cirrhotic Rats

et al. 1989

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Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4-induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol-treated rats had significantly lower cardiac output (-31%) and heart rate (-26%) than controls (p less than 0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 +/- 0.4 vs. 6.3 +/- 0.5 ml per min.100 gm in controls, p less than 0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 +/- 0.2 vs. 2.0 +/- 0.1 mmHg per ml per min.100 gm body weight (not significant)]. Hence, the fall in portal pressure (-19%) was expected from the decrease in portal inflow (-24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral vessels, since beta-blockade does not modify portal vascular resistance in cirrhosis.

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“…Furthermore, a number of studies have found that in cirrhosis splanchnic blood flow, i.e. flow entering the portal system, is increased by approximately 40-50%; this has been shown in a variety of experimental models: partial ligature of the portal vein (Blanchet and Lebrec, 1982;Groszman et al, 1982;Lebrec and Blanchet, 1985;Vorobioff et al, 1984), chemicallyinduced cirrhosis (Fernandez-Munoz et al, 1985) and biliary cirrhosis (Bosch et al, 1983). The pressure-flow relationship in the portal system is impaired, as when flow is reduced to normal values, portal pressure remains high Kroeger and Groszmann, 1985a;Sikuler and Groszmann, 1986a).…”

Section: Physiopathology Of Portal Hypertensionmentioning

confidence: 95%

Hepatic circulation: Potential for therapeutic intervention

Ballet

1990

Pharmacology & Therapeutics

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In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.

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Increased Blood Flow Through the Portal System in Cirrhotic Rats

Cited by 303 publications

References 14 publications

The calcium‐channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

The calcium‐channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

Propranolol Decreases Portal Pressure Without Changing Portocollateral Resistance in Cirrhotic Rats

Hepatic circulation: Potential for therapeutic intervention

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