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.     

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.     

ICI 169,369 selectively blocks 5-hydroxytryptamine2 receptors and lowers portal pressure in portal hypertensive rats

The contractile effects of 5-hydroxytryptamine on isolated portal veins and superior mesenteric veins of portal hypertensive rats (portal vein constricted) were antagonized competitively by ICI 169,369. The equilibrium dissociation constant of 1-3 nM for ICI 169,369, estimated in the veins, agrees with affinity estimates for arterial 5-hydroxytryptamine2 receptors. The receptors of portal veins of sham-operated rats had the same affinity for ICI 169,369 as the receptors of portal hypertensive rats. The systemic administration of ICI 169,369 to portal hypertensive rats decreased portal pressure from 13.0 +/- 0.4 to 11.3 +/- 0.5 mmHg (p less than 0.01) but did not affect arterial pressure. ICI 169,369 induced nonsignificant changes in both portal venous inflow and portocollateral resistance, as estimated by the radioactive microsphere technique. It is estimated that the combined changes in portal flow and resistance could explain the decrease in portal pressure. The results are consistent with an involvement of 5-hydroxytryptamine, acting through 5-hydroxytryptamine2 receptors, in prehepatic portal hypertension.     

Echo-Doppler evaluation of acute flow changes in portal hypertensive patients: flow velocity as a reliable parameter

In order to evaluate the behavior of the portal vein cross-sectional area during changes in portal flow, two groups of subjects were analyzed in two blinded cross-over studies using echo-Doppler flowmetry. The first group (I) consisted of 21 patients with cirrhosis and 16 controls. They received a standardized meal which is known to increase portal flow. The second group (II) consisted of 31 patients with cirrhosis who received a dose of propranolol which is known to decrease portal flow. In Group I, 30 min after the meal, the portal vein blood velocity increased by 35 +/- 6% (p less than 0.01) in cirrhotic patients and by 55 +/- 5% (p less than 0.01), in normal subjects. The portal vein cross-sectional area increased significantly in normal subjects (22 +/- 2%, p less than 0.01) but not in cirrhotic patients (4 +/- 2%, n.s.). In Group II, 2 h after propranolol, there was a significant decrease in portal blood velocity (-14 +/- 2%), whereas the portal vein cross-sectional area did not show any significant changes. These data demonstrate that, in portal hypersensitive patients, the portal area measured by echo-Doppler flowmetry can be assumed to be constant and hence its calculation to estimate changes in portal blood flow can be omitted. Therefore, the use of blood velocity alone is suggested to monitor acute changes in flow in portal hypertension using Doppler flowmetry. The elimination of the portal vein cross-sectional area measurement simplifies the quantitative calculation of portal hemodynamics and increases the reliability of the technique by avoiding a source of error.     

Propranolol and haemodynamic response in cirrhosis.

In the present study, we compared cirrhotic patients who had a decrease in the hepatic venous pressure gradient after propranolol intake to patients without a decrease. Twenty patients with cirrhosis and oesophageal varices were investigated during hepatic vein catheterization before and 90 min after an oral dose of 80 mg propranolol. The hepatic venous pressure gradient decreased by 12.6% (19.0 +/- 4.7 to 16.3 +/- 3.6 mm Hg, p less than 0.05). Eight (40%) out of 20 patients had a decrease of less than 10% in protal pressure (non-responders). Responders had a higher baseline cardiac index than non-responders (3.79 +/- 0.74 vs. 2.83 +/- 0.53 1.min-1.m-2; p less than 0.01). No difference in the effect of propranolol on portal pressure was observed between patients with or without ascites, or between Child-Turcotte A, B, and C class patients. Our results suggest that cirrhotic patients who respond to oral propranolol with a decrease in portal pressure are more hyperdynamic than those without a significant fall in portal pressure.     

Carvedilol, a new nonselective beta-blocker with intrinsic anti- Alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis.

Only some patients show a substantial hepatic venous pressure gradient (HVPG) reduction after propranolol, which makes it desirable to investigate drugs with greater portal hypotensive effect. The aim of this study was to investigate whether carvedilol, a nonselective beta-blocker with anti-alpha1-adrenergic activity, may cause a greater HVPG reduction than propranolol. Thirty-five cirrhotic patients had hemodynamic measurements before and after the random administration of carvedilol (n = 14), propranolol (n = 14), or placebo (n = 7). Carvedilol markedly reduced HVPG, from 19.5 +/- 1.3 to 15.4 +/- 1 mm Hg (P <.0001). This HVPG reduction was greater than after propranolol (-20.4 +/- 2 vs. -12.7 +/- 2%, P <.05). Moreover, carvedilol decreased HVPG greater than 20% of baseline values or to 相似文献   

Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in awake portal hypertensive rats

The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the beta-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 +/- 13 to 293 +/- 10 beats per min (mean +/- S.E.). Cardiac output significantly decreased from 54 +/- 3 to 42 +/- 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 +/- 1 to 18 +/- 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 +/- 17 to 368 +/- 31 dyne per sec per cm5 x 10(3). However, portal pressure showed only an insignificant decrease from 14.9 +/- 1.1 to 14.1 +/- 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 +/- 2 to 66 +/- 4 dyne per sec per cm5 x 10(3), p less than 0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doppler hemodynamic study in portal hypertension and hepatic encephalopathy

BACKGROUND/AIMS: The aim of our study was to evaluate and compare the differences in the parameters of portal hypertension in two groups of patients with liver cirrhosis, with and without hepatic encephalopathy (HE). METHODOLOGY: 30 patients with liver cirrhosis, 17 (56.7%) of them with HE, were investigated by clinical, neurological, laboratory, endoscopic methods and with color Doppler ultrasonography (CDU) at the Institute for Digestive Diseases, Clinical Center of Serbia, Beograde. RESULTS: Significant correlation was found between the diameters of the right liver lobe and the portal vein (p=0.01), and also between the diameters of the spleen and splenic vein (p=0.0002), in both groups of patients. Mean portal vein diameter significantly increases (p=0.01) in patients with HE (14.87 +/- 1.86mm), compared to those without HE (13.2 +/- 2.31mm), while mean splenic vein diameter was not significantly different in the two groups. In patients with ascites, CDU showed significantly lower (p=0.03) portal flow velocity (11.87 +/- 6.25cm/ sec), compared to those without ascites (14.33 +/- 4.41cm/sec). Splenic flow velocity was not significantly different (16.00 +/- 6.60cm/sec with ascites and 14.61 +/- 5.29cm/sec without ascites). In patients with HE, portal flow velocity was significantly lower (9.00 +/- 5.41cm/sec) compared to those without HE (14.0 +/- 7.03cm/sec) (p=0.04). Mean splenic flow velocity was significantly lower (p=0.03) in patients with HE (12.60 +/- 4.16cm/sec), compared to those without HE (17.77 +/- 5.91cm/sec). Portal flow velocity shows linear decrease, related to the increase of the liver damage (Child-Pugh score), while splenic velocity was not related to this parameter. CONCLUSIONS: Ultrasonographic parameters of portal hypertension show significant correlation between the diameters of liver/portal vein and spleen/splenic vein. Portal hemodynamic parameter (blood flow velocity) is significantly related to the stages of liver damage, presence of ascites and HE, while splenic hemodynamics is specific and not directly related to these parameters.     

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)     

Analysis of the characteristics of the flow velocity waveforms in left atrial small arteries and veins in the dog

To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We intended particularly to examine the influence of atrial contraction and relaxation on velocity waveforms to obtain some insight into the nature of the mechanical force acting on the atrial intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter of about 150-500 microns were chosen for the measurements because their walls are transparent to laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of cyanoacrylate when good-quality Doppler signals were consistently observed. Additional experiments with three dogs were performed to observe the blood velocities in the atrial artery and vein during arrhythmia. The blood velocity waveform in the artery was similar to the pattern of aortic pressure during ventricular ejection (peak velocity, 18.8 +/- 7.8 cm/sec) but was characterized by a pronounced dip during atrial contraction. The temporal coincidence between the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 micrograms i.v.), the acceleration rate of the forward flow velocity increased by 176% (p less than 0.05), and reverse flow appeared during atrial contraction in five cases out of eight (p = 0.013). The blood flow velocity in atrial small veins, on the other hand, was predominant during atrial contraction (peak velocity, 15.6 +/- 5.8 cm/sec). Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (p less than 0.01). Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in veins. The phase opposition between arterial inflow into and venous outflow from the atrial myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial myocardial contraction impedes atrial inflow and promotes venous outflow from atrial capacitance vessels.     

Duplex-Doppler ultrasonography in the evaluation of cirrhotic patients with portal hypertension and in the analysis of their response to drugs

Sixteen patients (15 males, aged 48-70) affected by liver cirrhosis and oesophageal varices were subjected to duplex-Doppler ultrasonographic study (DDUS). Four patients (three with a portal thrombosis and one with a hepatofugal portal flow) were excluded from the subsequent pharmacological test. The twelve remaining patients took part in a double blind cross-over study that evaluated the variations of heart rate (HR), mean systemic arterial pressure (SAP), portal vein diameter (PVD), maximal and mean portal flow velocity (PFV) after the administration of either 40 mg of propranolol or placebo per os, on two consecutive days. Propranolol caused no significant variation in mean SAP and in PVD, whereas it reduced the HR from 67.7 +/- 8.0 to 58.4 +/- 7.0 beats/min (mean +/- s.d.; P less than 0.001); the maxPFV dropped from 18.2 +/- 5.4 to 14.0 +/- 3.7 cm/s (P less than 0.001) and the meanPFV dropped from 15.3 +/- 4.1 to 13.2 +/- 3.1 cm/s (P less than 0.005). No significant variation was observed with placebo. After propranolol administration eight patients exhibited a significant maxPFV decrease, whereas the other four patients exhibited only a drop in HR, suggesting either drug inefficacy, inappropriate dosage or inadequate duration of treatment. DDUS is the only non-invasive method for the examination of the portal vein system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nipradilol, a new β-blocker with vasodilatory properties, in experimental portal hypertension: A comparative haemodynamic study with propranolol

The haemodynamic effects of nipradilol, a new non-selective β-adrenoreceptor blocker with vasodilating actions like nitroglycerin, were examined in rats with portal hypertension due to portal vein stenosis. Portal hypertensive rats were divided into five groups receiving infusion of placebo, 3 mg of propranolol, 300, 600 and 1200 μg of nipradilol. At its highest dose, nipradilol achieved a reduction of 34.4 ± 4.4% in heart rate which was similar to that in the propranolol group (36.5 ± 2.4%). Also for other systemic haemodynamic parameters, the nipradilol 1200 μg group exhibited changes not significantly different from those in the propranolol group; mean arterial pressure (- 13 vs - 14%), cardiac index (- 37 vs - 31%) and systemic vascular resistance (+ 29 vs+ 32%). In contrast to the similar changes in the systemic circulation, a 1200 μg dose of nipradilol lowered portal pressure significantly more than propranolol (- 4.3 ± 0.6 vs - 2.9 ± 0.2 mmHg, P≤ 0.05). Nipradilol then reduced portal blood flow by 22% (P≤ 0.05) without a significant change in portocollateral resistance. On the other hand, propranolol not only caused a reduction in portal blood flow of 30% (P≤ 0.01), but also an increase in portocollateral resistance of 21% (P≤ 0.05). The results suggest that nipradilol may ensure a more effective control of portal hypertension than propranolol, presumably via its venodilatory action on portocollateral vessels.     

Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80-mg dose of propranolol. Baseline azygos and renal venous norepinephrine levels were significantly higher than arterial norepinephrine levels (+20%, p less than 0.005; and +28%, p less than 0.001, respectively). Hepatic venous norepinephrine and all venous epinephrine values were below the arterial values (all p less than 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p less than 0.01; and +93%, p less than 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p less than 0.01), whereas hepatic venous norepinephrine and epinephrine remained unchanged. Azygos and hepatic blood flow decreased after propranolol intake (-27%, p less than 0.05; and -16%, p less than 0.01, respectively). Azygos spillover of norepinephrine (an estimate of locally released norepinephrine delivered to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained through superior portalsystemic collaterals and in the kidneys. The increase in circulating catecholamines after propranolol intake is probably due to a combination of further enhancement of sympathetic activity and a decrease in catecholamine degradation.     

Enhancement of portal pressure reduction by the association of isosorbide-5-mononitrate to propranolol administration in patients with cirrhosis

This study investigated whether oral doses of isosorbide-5-mononitrate, a preferential venous dilator that decreases portal pressure, could enhance the effects of propranolol on portal hypertension. Taking part in the study were 28 patients with cirrhosis and portal hypertension. Twenty patients (group 1) had hemodynamic measurements in baseline conditions after beta-blockade by intravenous administration of propranolol and after receiving oral doses of isosorbide-5-mononitrate. The remaining eight patients (group 2) were given oral isosorbide-5-mononitrate while receiving chronic propranolol therapy. In group 1, propranolol significantly reduced portal pressure (estimated as the gradient between wedged and free hepatic venous pressures) from 21.5 +/- 3.9 to 18.6 +/- 4.2 mm Hg (-13.7%, p less than 0.001), azygos blood flow (-38%, p less than 0.001), hepatic blood flow (-12.8%, p less than 0.05), cardiac output (-24.5%, p less than 0.001) and heart rate (-18.4%, p less than 0.001) without significant changes in mean arterial pressure. Addition of oral isosorbide-5-mononitrate caused a further and marked fall in portal pressure (to 15.7 +/- 3.1 mm Hg, p less than 0.001), without additional changes in azygos blood flow but with significant additional reductions in hepatic blood flow (-15.5%, p less than 0.05), cardiac output (-11.5%, p less than 0.001) and mean arterial pressure (-22%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Portal blood velocity and flow in aging man

The portal blood velocity and flow were measured by means of pulsed echo-Doppler in 60 normal subjects of 4 different age groups (less than or equal to 40, 41-55, 56-70, greater than or equal to 71 years). All subjects had normal routine liver function tests and no history of liver disease. Portal blood velocity decreased from 15.7 +/- 3.2 cm/s in younger subjects to 12.4 +/- 1.7 in subjects over 71 years (ANOVA: p = 0.005). Similarly portal blood flow decreased (p = 0.025). Both portal blood velocity and flow were inversely correlated with age (r = -0.583 and -0.505, respectively). No changes in portal vein diameter were observed. The age-related decline in portal flow may account for the decrease in hepatic blood flow previously documented in the elderly.     

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly reduced portal pressures (24 +/- 1 vs 32 +/- 1 cm saline), macroscopic mucosal damage (24 +/- 1 vs 39 +/- 4% of mucosa), and histologic deep necrosis (36 +/- 2 vs 61 +/- 4% of mucosal length). Increased dosage of propranolol to 4 mg did not produce any further reduction of portal pressure or mucosal damage. Central venous and systemic arterial pressures were not significantly altered by propranolol. The extent of mucosal damage correlated with levels of portal pressure (P less than 0.01) in portal hypertensive rats. Sham-operated normotensive rats had less macroscopic mucosal damage (26 +/- 4%) than portal hypertensive rats, and propranolol did not affect the extent of ethanol-induced damage or portal pressures in these animals. We conclude: (1) Propranolol is effective in reducing extent of ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in sham-operated controls; (2) this effect correlates with reduction of portal pressure; and (3) our study supports the clinical impression that reducing portal pressure may be one approach for the prevention and therapy of gastric mucosal damage in portal hypertension.     

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.     

Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension.

To establish the sensitivity and specificity of the mean portal flow velocity in the diagnosis of portal hypertension, a population of 304 consecutive cirrhotic patients, in whom 246 abdominal Doppler examinations were performed, was prospectively analysed between June 1988 and December 1990. To avoid equipment-related variability only examinations performed using the same equipment were considered. Further inclusion criteria were the absence of portal vein thrombosis or reversed flow in the portal vessels and the absence of spontaneous, ultrasonographically detectable, portosystemic shunts. The parameter evaluated was mean portal flow velocity calculated directly from the Doppler trace by specific, operator-independent, software. 123 patients satisfied the inclusion criteria. As a control group 60 healthy age- and sex-matched subjects were examined. Mean portal flow velocity was significantly lower in cirrhotic patients than healthy subjects (13.0 +/- 3.2 cm/s vs. 19.6 +/- 2.6 cm/s; p < 0.001). There was also a decrease in mean portal flow velocity in cirrhotics in each Child-Pugh category (13.8 +/- 2.8 cm/s in Child-Pugh A class; 12.1 +/- 3.5 cm/s in Child-Pugh B class and 11.0 +/- 2.4 cm/s in Child-Pugh C class) with a statistically significant difference between each Child-Pugh category and healthy subjects (p < 0.001), between Child-Pugh A and B (p < 0.01) and between Child-Pugh A and C (p < 0.005). The sensitivity and specificity of mean portal flow velocity in the detection of portal hypertension was then analyzed with the receiver operating characteristic curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 +/- 35 days of continuous oral administration (mean dose = 158 +/- 63 mg per day). Baseline portal pressure was 21.7 +/- 7.2 mm Hg. It decreased after 60 min to 17.2 +/- 5.5 mm Hg (p less than 0.01) and after long-term administration of propranolol to 16.1 +/- 5.7 mm Hg (p less than 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 +/- 1.2 liters X min-1 X m-2. It decreased after 60 min to 3.9 +/- 1.4 liters X min-1 X m-2 (p less than 0.01) and to 3.6 +/- 1.0 liters X min-1 X m-2 after long-term administration (p less than 0.001). Baseline heart rate was 85 +/- 11 beats per min. It decreased after 60 min to 75 +/- 9 (p less than 0.001) and after long-term administration to 62 +/- 6 (p less than 0.001) beats per min. Baseline mean arterial pressure was 108 +/- 11 Hg. It decreased after 60 min to 97 +/- 14 mm Hg (p less than 0.01) and after long-term administration to 103 +/- 14 mm Hg (not statistically significant).(ABSTRACT TRUNCATED AT 250 WORDS)