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)     

Haemodynamic effects of a combination of propranolol and clonidine in patients with post-hepatitic cirrhosis

Abstract The haemodynamic effects of a combination of propranolol and clonidine were evaluated in 20 patients with post-hepatitic cirrhosis. Haemodynamic measurements were taken before and 30 min after an intravenous injection of 0.1 mg/kg of propranolol. Thereafter, each patient was given an oral dose of 150 μ g of clonidine and re-measured 60 min later. In this series, eight patients were defined as 'non-responders' (a decrease in hepatic venous pressure gradient of < 10%) after propranolol treatment. Of both the responders and non-responders, propranolol caused expected decreases in the cardiac index and heart rate while mean arterial pressure remained unchanged. Of the propranolol responders, a significant decrease in hepatic venous pressure gradient was observed. After the addition of clonidine, in both the responders and non-responders there was a further decrease in hepatic venous pressure gradient with a concurrent drop in mean arterial pressure, but cardiac index and heart rate remained unaltered. In conclusion, the combination of propranolol and clonidine in post-hepatitic cirrhotic patients enhanced the reduction of portal pressure achieved by propranolol alone. The beneficial effects of the combination of the two in the reduction of portal pressure appeared to be similar in both the propranolol responders and non-responders. However, the drop in mean arterial pressure following the addition of clonidine may be hazardous to cirrhotic patients.     

Portal pressure response to losartan compared with propranolol in patients with cirrhosis

OBJECTIVES: Losartan, an angiotensin II receptor blocker, has portal hypotensive effects. This study evaluates the effect of losartan on portal pressure after 14 days and compares it with that of propranolol. METHODS: A total of 39 individuals with cirrhosis were randomized into two groups of 19 and 20 patients each and were treated with losartan and propranolol, respectively. Hepatic venous pressure gradient was measured at baseline and on day 14 of therapy. Responders to therapy had hepatic venous pressure gradient reduction of >/=20% of baseline value. RESULTS: With losartan, 15 of 19 (78.94%) patients were responders and with propranolol, nine of 20 (45%) patients were responders (p < 0.05). Although the hepatic venous pressure gradient reduction (i.e., percentage from baseline) with losartan (26.74 +/- 21.7%) was higher than with propranolol (14.52 +/- 32%), the difference was not significant. The reduction in hepatic venous pressure gradient with losartan was contributed mainly by a significant drop of wedge hepatic venous pressure from 32.42 +/- 6.61 mm of Hg to 28.31 +/- 5.09 mm of Hg (p < 0.05) compared to that with propranolol, which was from 34.55 +/- 5.41 mm of Hg to 32.75 +/- 8.13 mm of Hg (p > 0.05). Responders among alcohol-abusing patients were significantly higher with losartan (81.8%) compared to those on propranolol (27.2%; p < 0.05). In the losartan group, all seven nonascitic cirrhotic individuals, as compared with two of five in the propranolol group, responded to the drugs. During the study, no significant side effects were observed in either group (who were not receiving diuretics) or in follow-up with diuretics. CONCLUSIONS: Losartan is as effective as propranolol in reducing portal pressure in cirrhotic patients who are not receiving diuretics. Losartan is also superior to propranolol for achieving target level hepatic venous gradient for prevention of variceal bleeding in nonascitic and alcohol-abusing cirrhotic patients.     

Short-term effects of propranolol on portal venous pressure

The present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 +/- 4.1 mm Hg. It decreased significantly 2 hr after the oral administration of 40 mg of propranolol to 15.7 +/- 4.2 mm Hg (a mean reduction of 13.4 +/- 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (greater than 20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of "responders" (those that reduced hepatic venous pressure gradient greater than 10%) and "nonresponders" (hepatic venous pressure gradient reduction less than 10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in the heart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction in hepatic venous pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of portal pressure, anorectal varices and hemorrhoids in cirrhotic patients.

In a prospective study of 103 consecutive cirrhotic patients a high prevalence (43%) of anorectal varices was found compared with only 2% in 103 age- and sex-matched control subjects (p less than 0.001). However, there was no significant difference between the prevalences of hemorrhoids in cirrhotic patients and in control subjects (79% vs. 83%, p greater than 0.05). The hepatic venous pressure gradient of cirrhotic patients with anorectal varices was similar to cirrhotic patients without anorectal varices (14 +/- 6 mmHg, n = 22, vs. 16 +/- 7 mmHg, n = 39, p greater than 0.05. There was no significant difference in the hepatic venous pressure gradient between cirrhotic patients with and without hemorrhoids (15 +/- 6 mmHg, n = 47, vs. 16 +/- 8 mmHg, n = 14, p greater than 0.05). The prevalence of anorectal varices and hemorrhoids in cirrhotic patients had no relation to Child-Pugh's grading, esophageal varices with and without sclerotherapy and ascites. We conclude that anorectal varices are common in cirrhotic patients. Anorectal varices and hemorrhoids are not related to the degree of portal pressure.     

Effects of molsidomine, a long acting venous dilator, on portal hypertension. A hemodynamic study in patients with cirrhosis.

The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension.     

Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study

OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.     

The portal pressure response to beta-blockade is greater in cirrhotic patients without varices than in those with varices

BACKGROUND & AIMS: Nonselective beta-blockers are effective in reducing portal pressure in cirrhotic patients. However, this beneficial effect is highly variable and may depend on the extent of portal system collateralization. The aim of this study was to compare portal pressure response with timolol, a nonselective beta-blocker, in cirrhotic patients with and without varices. METHODS: Portal and systemic hemodynamics were measured before and after a single oral dose of 10 mg of timolol in 50 patients with cirrhosis and portal hypertension, 15 with and 35 without esophageal varices. RESULTS: Timolol significantly decreased portal pressure in all patients (mean reduction, 20% +/- 13%; P < 0.0001). The reduction in hepatic venous pressure gradient was greater in patients without varices (-24% +/- 14%) than in those with varices (-12% +/- 8%) (P < 0.01). A decrease in the hepatic venous pressure gradient of <12 mm Hg was achieved in 7 of 12 (58%) patients without varices and a baseline pressure gradient of <12 mm Hg, but only in 3 of 15 patients with varices (20%) (P < 0.01). CONCLUSIONS: Timolol is effective in reducing portal pressure in cirrhotic patients, more so in patients without varices, suggesting that nonselective beta-blockers will be more effective in the treatment of portal hypertension when administered at early stages, before the development of varices. (Gastroenterology 1997 Jun;112(6):2012-6)     

Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis

The effects of beta-blockade with propranolol and of alpha-adrenergic stimulation with methoxamine, a powerful alpha-agonist, on azygos blood flow and on systemic and hepatic haemodynamics were investigated in 26 cirrhotic patients with portal hypertension. Beta-adrenergic blockade with propranolol (n = 12), evidenced by a significant reduction of heart rate (-17 +/- 1%, P less than 0.001) and cardiac index (-17 +/- 2%, P less than 0.001), caused a mild but significant decrease of hepatic venous pressure gradient (-10 +/- 2%, P less than 0.05) and a marked fall of azygos venous blood flow (-31 +/- 5%, P less than 0.05). Alpha-adrenergic stimulation with methoxamine (n = 14), manifested by a significant increase of mean arterial pressure (19 +/- 2%, P less than 0.001), mimicked the effects of propranolol on hepatic venous pressure gradient (-10 +/- 4%, P less than 0.05) and cardiac index (-11 +/- 2%, P less than 0.001). However, azygos blood flow was not significantly reduced by methoxamine (0.7 +/- 0.1 vs 0.6 +/- 0.1 l/min). On the contrary, hepatic blood flow was significantly reduced by methoxamine (-19 +/- 4%, P less than 0.01) but not by propranolol (-7 +/- 7%, ns). Similarly, in 8 patients who received methoxamine after being beta-blocked by propranolol, azygos blood flow, that was markedly reduced by beta-blockade, did not experience a further reduction but increased slightly by alpha-adrenergic stimulation, while hepatic blood flow, that was not reduced by propranolol, decreased significantly during the subsequent methoxamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacological therapy of portal hypertension--focused on Korean data]

Portal hypertension as a consequence of liver cirrhosis is responsible for serious complications such as variceal bleeding, ascites and hepatic encephalopathy. Successful pharmacological treatment of portal hypertension can prevent the risk of the variceal bleeding, and contribute to reduce the morbidity and mortality in patients with liver cirrhosis. To identify the effect of drugs on portal hypertension, portal pressure was evaluated accurately before and after the drug administration. The hepatic venous pressure gradient has been accepted as the gold-standard method for assessing the severity of portal hypertension and the response to drug treatment. The mean hepatic venous pressure gradient was 15.1+/-5.4 mmHg in Korean cirrhotic patients who had experienced variceal bleeding. Non-selective beta blockers are the treatment of choice for primary and secondary prevention of variceal bleeding. The dose of propranolol should be subsequently adjusted until the resting heart rate had been reduced by 25% or less than 55 beats per minute. It has been reported that the optimal dose of propranolol is variable due to racial differences in cardiovascular receptor sensitivity. In Korean patients with portal hypertension and liver cirrhosis, the mean required dose of propranolol to reach target heart rate was 165 mg (range; 80-280 mg). This review covers mainly the results of the pharmacological therapy of portal hypertension in Korean cirrhotic patients.     

Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.     

Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage

In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.     

Hemodynamic effect of spironolactone in liver cirrhosis and propranolol-resistant portal hypertension.

OBJECTIVE: In a proportion of patients with liver cirrhosis, portal pressure does not decrease adequately with propranolol. These patients may benefit from another drug that may reduce portal pressure. We evaluated the role of spironolactone, alone or with propranolol, in such patients. METHODS: Patients with cirrhosis, with or without ascites, with esophageal varices and with hepatic venous pressure gradient exceeding 12 mmHg, which did not show a 20% reduction after an 80-mg oral dose of propranolol, were studied. They were allocated to receive spironolactone 100 mg orally once daily either alone (group 1, n=10) or with propranolol 40 mg orally twice daily (group 2, n=10), for 7 days, after which the hemodynamic study was repeated. RESULTS: Hepatic venous pressure gradient decreased in those receiving spironolactone and propranolol (p=0.007); 5 patients in group 1 and 7 in group 2 showed a reduction in hepatic venous pressure gradient by more than 20%. However, the reduction produced by spironolactone alone (20.5 [31.3]%) was not significantly different from that produced by combination therapy (30.3 [25.9]%; p=0.46). CONCLUSION: Spironolactone in combination with propranolol achieves adequate reduction (> or = 20%) in hepatic venous pressure gradient in propranolol-resistant portal hypertension in patients with liver cirrhosis. Spironolactone alone was also effective in some patients.     

Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients

Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 +/- 2.7 mmHg. It decreased significantly to 13.3 +/- 2.0 mmHg (p less than 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 +/- 4.0 to 20.1 +/- 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function. This study confirms evidence in favor of a role for 5-hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

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   

Comparison of portal vein velocity and the hepatic venous pressure gradient in assessing the acute portal hemodynamic response to propranolol in patients with cirrhosis

OBJECTIVE: The aim of this prospective study was to compare noninvasive Doppler sonography and invasive measurement of the hepatic venous pressure gradient (HVPG) to determine the acute portal hemodynamic response to propranolol in patients with liver cirrhosis. METHODS: In a blinded study design, portal vein velocity (PVV) and HVPG were simultaneously assessed in 11 cirrhotic patients for 4 h after oral ingestion of 40 mg propranolol. RESULTS: Both HVPG (17.2% +/- 4.3%, p < 0.0001) and PVV (15.6% +/- 2.1%, p < 0.0002) showed a highly significant reduction during the study period versus baseline. Based on HVPG measurements, four patients (36%) were classified as nonresponders. These patients had a significantly lower PVV reduction compared to the responders (responders: 18.8% +/- 2.0% vs nonresponders: 10.0% +/- 2.1%, p < 0.05). Nonresponders were identified by Doppler sonography with a sensitivity of 1.0, specificity of 0.86, and positive predictive value of 0.9 when a threshold of 20% PVV reduction 120 min after drug intake was applied. CONCLUSIONS: Doppler sonography is a useful tool for assessment of the acute portal hemodynamic effect of propranolol. To distinguish portal hemodynamic nonresponders from responders to propranolol, PVV measurements should be carried out 2 h after drug administration, and PVV reduction should be not <20% in propranolol responders.     

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)     

The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics

The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy.     

Effect of propranolol on portosystemic collateral circulation in patients with cirrhosis

Propranolol has been demonstrated to be effective in lowering portal pressure in cirrhotic patients. This effect is mediated by a reduction of splanchnic arterial inflow and a consequent decrease of portal vein and portocollateral blood flow. Although experimental studies suggest a direct effect of the drug on portocollateral circulation, little information exists about relative flow changes occurring in the portal vein and in collateral veins feeding esophageal varices. This study addressed the problem in 12 cirrhotic patients selected on the basis of feasibility of Doppler flowmetry in both the portal and left gastric veins. Caliber, flow velocity and flow volume in both vessels were measured by Doppler ultrasound before and at 60, 120 and 180 min after an oral dose of 40 mg propranolol, together with heart rate and mean arterial pressure. A significant decrease in heart rate (-17.6% +/- 1.1%, p less than 0.001) and mean arterial pressure (-10.6% +/- 0.9%, p less than 0.005) confirmed effective beta-blockade. Baseline flow velocity was significantly lower in the portal vein than in the left gastric vein (12.4 +/- 0.6 vs. 15.4 +/- 1.5 cm/sec, p less than 0.05). Maximal hemodynamic effect was reached at 120 min after administration of propranolol. The vessel caliber did not change significantly. Flow velocity fell from 12.4 +/- 0.6 to 10.4 +/- 0.7 cm/sec in the portal vein (p less than 0.05) and from 15.4 +/- 1.5 to 11.1 +/- 0.9 cm/sec in the left gastric vein (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)