Different hemodynamic patterns of alcoholic and viral endstage cirrhosis: analysis of explanted liver weight, degree of fibrosis and splanchnic Doppler parameters

OBJECTIVE: In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis. MATERIAL AND METHODS: Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study. RESULTS: In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246+/-295 g versus 1070+/-254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49+/-0.36 ml g(-1) min(-1) versus 0.85+/-0.56 ml g(-1) min(-1), p=0.004) and hepatic pulsatility indices were higher (1.45+/-0.31 versus 1.26+/-0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7+/-5.5% versus 11.0+/-4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p<0.001) but not in alcoholic disease. CONCLUSIONS: A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.     

The hepatic microcirculation in the isolated perfused human liver

In cirrhosis, capillarization of sinusoids could result in impaired exchanges between the hepatocytes and the blood perfusing the liver and contribute to liver failure irrespective of the metabolic capacity of the liver. To characterize anomalies of the hepatic microcirculation, we used the multiple-indicator dilution approach in isolated perfused livers obtained from patients with cirrhosis at the time of transplantation, and from organ donors with normal or near-normal livers or hepatic steatosis. In organ donors, the sinusoidal volume and the permeability of sinusoids to albumin, sucrose, and water were found to be comparable to that of normal dog and rat livers. The sinusoidal volume and the extravascular volume (EVV) accessible to diffusible tracers were larger after hepatic artery than after portal vein injection, probably because of an unshared arterial sinusoidal bed. In cirrhotic livers, two kinds of alterations were found: the appearance of a barrier between the sinusoids and the hepatocytes (capillarization) and intrahepatic shunts. The extravascular space accessible to albumin decreased with increasing severity of cirrhosis, and the diffusion of sucrose in the space of Disse showed a barrier-limited pattern, instead of the normal flow-limited behavior. In cirrhotic livers, a correlation was found between the hepatic extraction of indocyanine green (ICG) and the extravascular space accessible to albumin (r = .84, P < .05), suggesting that the impaired access of this protein-bound dye to the hepatocyte surface contributed to its impaired elimination. Intrahepatic shunts were found between portal and hepatic vein (21% +/- 16% of portal flow), but not between hepatic artery and hepatic veins. We conclude that (1) the behavior of diffusible tracers in human livers with normal liver architecture is comparable to that reported in normal animals; (2) the permeability of sinusoids in cirrhotic livers is abnormal, (3) permeability changes are related to changes in liver function in cirrhosis. (Hepatology 1996 Jan;23(1):24-31)     

Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats.

BACKGROUND/AIMS: Increased intrahepatic vascular tone can be pharmacologically manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysfunction may lead to a decreased production of the potent endogenous vasodilator nitric oxide in cirrhotic livers. The aims of the study were to determine whether portal pressure can be lowered in vivo by injecting nitric oxide donors glyceryl trinitrate or nitroprusside directly in the portal vein and whether this is related to a decrease in intrahepatic resistance. METHODS: In anaesthetised CCl4 cirrhotic rats, intraportal doses of glyceryl trinitrate 0.5, 1 or 5 microg/kg/ min or nitroprusside 1, 5 or 10 microg/kg/min did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraportal infusion of glyceryl trinitrate 10 microg/kg/min or nitroprusside 20 microg/kg/min. RESULTS: Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 11.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm Hg and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05). Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66+/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/min/g liver; all p<0.05). Portal sinusoidal resistance was not altered by either drug. CONCLUSIONS: Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed.     

Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting

The present study investigated whether, in rats with portal hypertension due to cirrhosis of the liver induced by carbon tetrachloride, blood volume restitution following a hemorrhage produces an increase of portal pressure beyond control values, as observed in rats with prehepatic portal hypertension. Since carbon tetrachloride-induced cirrhosis caused mild portal-systemic shunting, in some of the cirrhotic rats (12 of 29 rats) portal-systemic shunting was enhanced by a transient (4 days) partial constriction of the portal vein, which was removed 1 week prior to the study. After baseline measurements of portal pressure and arterial pressure, 15 ml per kg of blood were withdrawn at a rate of 0.3 ml per min and reinfused 15 min later. After blood reinfusion, portal pressure and arterial pressure were measured again, and cardiac output, regional blood flows and portal-systemic shunting were determined using radioactive microspheres. Portal-systemic shunting was 78 +/- 11% of total blood flow in the cirrhotic rats that had temporary portal vein constriction, but only 5 +/- 2% (p less than 0.001) in those that did not. Blood volume restitution in low-portal-systemic shunting rats did not produce any significant modification in splanchnic or systemic hemodynamics. However, in rats with high portal-systemic shunting, blood volume restitution produced a significant increase in portal pressure (from 9.9 +/- 0.9 to 13.5 +/- 0.9 mmHg, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mixed endothelin receptor antagonist, SB209670, decreases portal pressure in biliary cirrhotic rats in vivo by reducing portal venous system resistance

BACKGROUND/AIMS: This study aimed to evaluate the hemodynamic effects of endothelin-1 or mixed endothelin receptor antagonist, SB209670 in cirrhotic rats, and to elucidate the role of endothelin in cirrhotic portal hypertension. METHODS: Secondary biliary cirrhosis was induced by bile duct ligation. Hemodynamics were studied using the radioactive microsphere technique. RESULTS: Plasma and hepatic endothelin levels in cirrhotic rats were significantly higher than those in normal rats (plasma, 9.0+/-1.3 vs. 2.6+/-0.5 pg/ml, p<0.001; liver, 74.8+/-13.3 vs. 12.6+/-2.5 pg/g wet tissue, p<0.001). Intraportal administration of endothelin-1 (3 nmol/kg) progressively raised portal pressure without an initial transient reduction, which was observed in systemic arterial pressure, in both cirrhotic and normal rats. SB209670 (5.4 micromol/kg) reduced portal pressure in cirrhotic rats (-19+/-5%, p<0.01) without modifying systemic arterial pressure and renal blood flow, but not in normal rats. This reduction was associated with reduced portal venous system resistance (vehicle, 2.5+/-0.2 vs. SB209670, 1.7+/-0.1 mmHg x min x 100 g bw/ml, p<0.01), but not with change in portal venous inflow and collateral blood flow. CONCLUSIONS: Mixed endothelin antagonist, SB209670, decreased portal pressure by reducing portal venous system resistance without modifying systemic arterial pressure and renal blood flow in cirrhotic rats. This result, together with the findings that plasma and hepatic endothelin levels were elevated in cirrhotic rats and that exogenous endothelin-1 increased portal pressure, provides further support for a role of endothelin in portal hypertension and suggests a potential use of mixed endothelin antagonist in the pharmacological treatment of portal hypertension.     

Interrelationship between splenic and superior mesenteric venous circulation manifested by transient splenic arterial occlusion using a balloon catheter

We examined the hemodynamic changes induced by transient splenic arterial occlusion using a balloon catheter to investigate the hemodynamic effect of transcatheter splenic arterial embolization--a procedure that has been used since its introduction in 1973 as therapy for hypersplenism and more recently for portal hypertension. The blood flow volume was measured in 20 patients with liver disease using an ultrasonic duplex system (Toshiba SAL50A/SDL-01A). The portal venous pressure was also measured via a 3F catheter using a transducer. The catheter was placed in position by substituting it for a 25-gauge needle that had been inserted into the portal vein under ultrasonic guidance percutaneously and transhepatically. Splenic arterial occlusion caused a drop in splenic venous blood flow from 708 +/- 487 to 241 +/- 155 ml per min, in portal venous blood flow from 993 +/- 439 to 807 +/- 419 ml per min and in portal venous pressure from 17.4 +/- 7.2 to 14.4 +/- 6.1 mm Hg. The latter two reductions were less than expected from the decrease in the splenic venous blood flow volume. This phenomenon was caused by an increase in the mesenteric venous blood flow from 475 +/- 126 to 630 +/- 270 mm per min. This increase may be due to a compensatory mechanism under the control of a regulatory loop in the liver or portal vein, and there seems to be a relationship between splenic and intestinal circulation in portal hypertension that maintains hepatic circulation.     

Spontaneous intermittent reversal of blood flow in intrahepatic portal vein branches in cirrhosis of the liver

The intrahepatic portal venous flow in cirrhosis of the liver was evaluated by percutaneous transhepatic portography and hepatic arteriography. Spontaneous reversal of flow in segmental portal vein branches was documented. Changes in hepatic arterial inflow and portal venous pressure may result in intermittent changes in the direction of flow in segmental portal venous branches within the cirrhotic liver. Segmental reversal of blood flow seems to be the precursor of total hepatofugal portal flow.     

Postprandial splanchnic haemodynamic changes in patients with liver cirrhosis and patent paraumbilical vein

OBJECTIVE: The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). METHODS: We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. RESULTS: We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. CONCLUSIONS: PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.     

Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats

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.     

The intrahepatic biliary epithelium in the guinea pig: is hepatic artery blood flow essential in maintaining its function and structure?

To determine whether hepatic artery blood flow is essential in maintaining the function and structure of bile ductules/ducts, the acute effects of hepatic artery ligation on bile secretion and hepatic ultrastructure were examined in anesthetized, bile duct-cannulated guinea pigs. Sixty minutes after hepatic artery ligation, spontaneous bile flow (5.08 +/- 0.4 microliter per min per gm liver) was virtually the same as that before hepatic artery ligation (5.31 +/- 0.3 microliter per min per gm), as were the choleretic effects of 10 CU per kg per 30 min secretin (7.14 +/- 0.9 vs. 7.21 +/- 0.9 microliter per min per gm), 300 micrograms per kg per 30 min glucagon (6.72 +/- 0.9 vs. 6.59 +/- 0.8 microliter per min per gm) and 60 mumoles per kg per 30 min glycochenodeoxycholate (6.43 +/- 0.6 vs. 6.45 +/- 0.6 microliter per min per gm). The failure of hepatic artery ligation to affect bile secretory function could not be attributed to the existence of collateral arterial blood flow to the liver. First of all, hepatic artery ligation resulted in diminishing significantly hepatic venous, but not portal, oxygen content. More importantly, in isolated guinea pig livers, perfused through the portal vein alone, secretin, glucagon and glycochenodeoxycholate produced changes in bile flow and composition similar to those seen in vivo. Electron microscopy showed no major ultrastructural changes of hepatic parenchyma and biliary epithelium 2 hr after hepatic artery ligation, or 2 hr after perfusing the liver through the portal vein alone save for some portal edema in the latter instance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis.

Thioacetamide-induced rat cirrhosis was characterized by single-cell necroses, fibrosis, nodular parenchyma, decrease in parenchymal volume density and an increase in liver weight per body weight so that the total amount of parenchyma was not altered. The glycogen content was normal, and signs of decompensation were not found. Isolated livers were single-pass perfused by way of both the hepatic artery and the portal vein. In the normal livers stimulation of the nerve plexuses around the hepatic artery or portal vein (7.5 Hz; 2 msec) and infusions of noradrenaline (1 mumol/L) by way of either vessel and of acetylcholine (10 mumol/L) by way of the artery only increased glucose output, reduced both portal and arterial flow and increased the intravascular pressures. Glucagon (0.5 nmol/L) augmented glucose release and had no hemodynamic effects. In chronically thioacetamide-injured livers all stimuli caused smaller metabolic alterations per gram of liver weight and decreased portal flow more and arterial flow less with stronger enhancements of intravascular pressures than in the controls. The lowered metabolic responsiveness per gram of cirrhotic liver was largely compensated by the increase in liver weight. Thus despite massive histological alterations and pronounced increases in stimulation-dependent resistances - predominantly in the portal system - cirrhotic rat livers responded in their glucose metabolism to nervous and hormonal stimuli in almost the same manner as normal livers.     

Effects of verapamil on hepatic and systemic hemodynamics and liver function in patients with cirrhosis and portal hypertension

The effects of verapamil on hepatic and systemic hemodynamics and on liver function were investigated in 10 patients with portal hypertension due to advanced micronodular cirrhosis to verify whether, as it has been suggested, this calcium channel blocker may improve liver function and reduce portal pressure in these patients. The oral administration of 100 mg of verapamil caused systemic vasodilation, evidenced by a significant reduction in mean arterial pressure (-8.1 +/- 7.6%, p less than 0.025) and systemic vascular resistance (-12.5 +/- 9.5%, p less than 0.001), and increased heart rate (+13.9 +/- 10.4%, p less than 0.01). However, no beneficial effect was noted on portal pressure evaluated by hepatic vein catheterization (baseline 19.8 +/- 4.0, verapamil 20.2 +/- 3.6 mmHg, NS), hepatic blood flow (1.45 +/- 0.64 vs. 1.47 +/- 0.62 liters per min, NS) and hepatic vascular resistance (1.314 +/- 611 vs. 1,266 +/- 513 dyn per sec per cm-5, NS). Similarly, no change was observed in portal blood flow, measured in six patients by pulsed Doppler flowmeter (0.94 +/- 0.30 vs. 0.89 +/- 0.35 liter per min, NS). In addition, verapamil did not increase the hepatic intrinsic clearance of these patients (0.20 +/- 0.07 vs. 0.19 +/- 0.06 liter per min, NS). This study suggests that verapamil is of no beneficial effect in patients with advanced cirrhosis of the liver.     

Increased blood flow through the portal system in cirrhotic rats

Portal venous pressure is the result of the interplay between portal venous blood flow and the vascular resistance offered to that flow. Whether portal hypertension is maintained only by an increased portal venous resistance or also by an increased blood flow within the portal venous system is still open to speculation. To resolve these differences, splanchnic and systemic hemodynamics were evaluated in cirrhotic rats, induced by CCl4. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. All cirrhotic rats had portal hypertension (portal venous pressure 13.5 +/- 1.1 vs. 9.0 +/- 0.5 mmHg, in normal control rats; p less than 0.01), but portal-systemic shunting in cirrhosis (31% +/- 13% vs. 0.2% +/- 0.02%; p less than 0.05) was variable, ranging from 1% to 97%. Portal venous inflow, the total blood flow within the portal system, was increased in cirrhotic rats (5.75 +/- 0.04 vs. 4.52 +/- 0.36 ml/min per 100 g; p less than 0.05). Total splanchnic arterial resistance was reduced in cirrhotic rats (3.3 +/- 0.2 vs. 5.8 +/- 0.5 dyn X s X cm-5 X 10(5); p less than 0.01). Portal venous resistance, however, was not abnormally elevated in cirrhotic rats (4.6 +/- 0.5 vs. 4.7 +/- 0.5 dyn X s X cm-5 X 10(4), p = NS). Splanchnic hemodynamics in cirrhotic rats demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venous inflow. The hemodynamic data in cirrhotic rats provided evidence that supports the role of an increased portal blood flow in portal hypertension and gives a quantitative definition of splanchnic hemodynamics in intrahepatic portal hypertension.     

Intact hepatocyte theory of impaired drug metabolism in experimental cirrhosis in the rat.

The elimination of propranolol by perfused livers of rats made cirrhotic by chronic carbon tetrachloride inhalation during phenobarbital treatment has been compared with control animals receiving only phenobarbital. Cirrhosis reduced propranolol clearance at a constant flow of 20 ml/min from 1.43 +/- 0.08 to 1.12 +/- 0.08 ml/min/g liver (P less than 0.025). In addition, an increase in intrahepatic shunting of 15-micron microspheres from 0.41 +/- 0.01 to 9.4 +/- 4.1% was found in cirrhotic livers (P less than 0.05). Finally, in cirrhotic livers, reducing blood flow did not produce the normal rise in hepatic extraction ratio, which actually fell from 0.873 +/- 0.021 at 20 ml/min to 0.836 +/- 0.025 at 15 ml/min and 0.823 +/- 0.026 at 10 ml/min. At each flow the observed extraction was significantly lower than that predicted to result from a reduced enzyme activity alone, consistent with the development of functionally significant intrahepatic shunts. An operational model is proposed that explains impaired drug metabolism in cirrhosis on the basis of the development of intrahepatic shunts which perfuse nonfunctioning tissue, while the remaining blood flow is exposed to a reduced mass of hepatocytes with an apparently normal amount of drug metabolizing enzyme (the intact hepatocyte theory).     

Relation of sinusoidal stenoses following hepatocyte swelling to hepatic vascular resistance in experimental liver cirrhosis

To investigate the significance of sinusoidal stenoses and a decrease in the sinusoidal bed due to hepatic cell swelling as a factor increasing hepatic vascular resistance in liver cirrhosis, hepatic vascular resistance in choline-deficient diet-induced cirrhotic rats was measured by an isolated liver perfusion method. In the cirrhotic rats, the swollen hepatic cells resulting from accumulation of fat droplets narrowed the sinusoids and decreased the sinusoidal bed. Consequently, the hepatic vascular resistance was increased by 2.7 times normal (8.60 +/- 2.32 mm H2O.ml-1.min; controls, 3.13 +/- 0.67 mm H2O.ml-1.min), and portal hypertension was also recognized (188.1 +/- 26.3 mm H2O; controls, 114.2 +/- 12.8 mm H2O). In the cirrhotic rats fed with ordinary rat pellets for 2 months, however, the sinusoidal stenoses and the decreased sinusoidal bed recovered to nearly normal as a result of disappearance of the fat droplets in the hepatic cells. The increased hepatic vascular resistance was decreased to 1.5 times normal (4.68 +/- 0.82 mm H2O.ml-1.min), and the elevated portal vein pressure was reduced (141.5 +/- 17.4 mm H2O). These findings clearly demonstrate that an important factor leading to an increase in hepatic vascular resistance is sinusoidal stenoses and a decrease in the sinusoidal bed resulting from swollen hepatic cells.     

Effects of glucose ingestion on hepatic hemodynamics in patients with liver disease by per-rectal portal scintigraphy using 99mTcO4- (direct intramural administration of radioisotope method)]

Effects of glucose (225 ml, 300 kcal) ingestion on hepatic hemodynamics was studied in ten patients with liver cirrhosis and eight patients with non cirrhotic liver disease by per-rectal portal scintigraphy using 99mTcO4- (direct intramural administration of radioisotope method). Initial portal blood flow index (IP) and collateral index (CI) were calculated from the time activity curve of heart and liver. The value of IP was not significantly changed between before and after glucose ingestion in cases with liver cirrhosis (before: 0.0160 +/- 0.0016, after: 0.204 +/- 0.106). In cases with non cirrhotic liver disease, the value of IP was significantly increased after glucose ingestion (before: 0.0381 +/- 0.0145, after: 0.0544 +/- 0.0194, p less than 0.02). These findings suggested increase in portal blood flow via inferior mesenteric vein to the cardiac blood flow. The value of CI before glucose ingestion was significantly increased in cases with liver cirrhosis (0.751 +/- 0.156) compared with that in cases with non cirrhotic liver disease (0.517 +/- 0.122), but no significant difference in values after glucose ingestion was found between these two groups.     

Effect of metoclopramide on portal blood flow in patients with liver cirrhosis, measured by the pulsed Doppler system

The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemodynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemodynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 +/- 1.1 to 10.8 +/- 1.2 cm/sec and from 769.0 +/- 87.7 to 707.9 +/- 84.2 ml/min, respectively (p less than 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p greater than 0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension.     

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (from 9.0 +/- 2.1 to 11.7 +/- 2.7 mmHg per liter per min, p less than 0.001), whereas mean arterial pressure did not change (77 vs. 78 mmHg). Propranolol significantly reduced hepatic artery blood flow (from 0.65 +/- 0.20 to 0.55 +/- 0.14 liters per min, p less than 0.01). However, reduction of hepatic artery blood flow (-12.9 +/- 7.3%) was significantly less than reduction of cardiac output (-21.1 +/- 5.2%, p less than 0.01). As a result, the fraction of the cardiac output delivered to the liver was significantly greater after propranolol (8.0 +/- 1.7%) than before (7.3 +/- 1.7%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic arterial buffer response in patients with advanced cirrhosis

Hepatic arterial buffer response (HABR) is considered an important compensatory mechanism to maintain perfusion of the liver by hepatic arterial vasodilation on reduction of portal venous perfusion. HABR has been suggested to be impaired in patients with advanced cirrhosis. In patients with hepatopetal portal flow, placement of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal venous liver perfusion. Accordingly, patients with severe cirrhosis should have impaired HABR after TIPS implantation. Therefore, the aim of this study was to investigate the effect of TIPS on HABR as reflected by changes in resistance index (RI) of the hepatic artery. A total of 366 patients with cirrhosis (Child-Pugh class A, 106; class B, 168; class C, 92) underwent duplex Doppler ultrasonographic examination with determination of RI and maximal flow velocity in the portal vein before and 1 month after TIPS placement. Portosystemic pressure gradient was determined before and after TIPS placement. In 29 patients with hepatofugal portal blood flow, RI was significantly lower than in 337 patients with hepatopetal flow (0.63 plus minus 0.02 vs. 0.69 plus minus 0.01; P <.001). TIPS induced a significant decrease of the RI in patients with hepatopetal flow (RI, 0.69 plus minus 0.01 before vs. 0.64 plus minus 0.01 after TIPS; P =.001) but not in patients with hepatofugal flow (RI, 0.63 plus minus 0.02 before vs. 0.63 plus minus 0.02 after TIPS; NS). This response was not dependent on the Child-Pugh class. In conclusion, our results suggest that some degree of HABR is preserved even in patients with advanced cirrhosis with significant portal hypertension.     

Hemodynamic effects of terbutaline, a beta 2-adrenoceptor agonist, in conscious rats with secondary biliary cirrhosis.

The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor agonist - were studied in conscious normal rats and in conscious rats with secondary biliary cirrhosis. Compared with those of normal rats, dose-response curves in cirrhotic rats indicated significantly decreased reactivity in arterial pressure and heart rate. Half-maximal effective dose was not significantly different between the two groups. Terbutaline induced significant, dose-dependent decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1 body wt) increased both cardiac output and portal tributary blood flow, thus mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to 22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The association of a decreased portal pressure and increased splanchnic blood flow suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal collateral vascular resistance.