Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used transesophageal real-time two-dimensional Doppler echography (TE2DD) to assess the effects of propranolol (n = 18, 6 mg each) and nitroglycerin (n = 18, 0.5 mg each) on blood flow in the intercostal veins, azygos vein, thoracic aorta, and esophagogastric varices. The primary disease in all of the patients was liver cirrhosis. Propranolol infusion markedly reduced the flow velocity in the varices, intercostal vein, azygos vein, and thoracic aorta (-24%, -41%, -34%, and -24%, respectively). It also significantly reduced the blood flow volume index (BFVI), defined as mean velocity in cm/sec X the square of the diameter in cm2 of both the azygos vein and the aorta (-34%, -21%, respectively). Nitroglycerin infusion did not cause significant changes in the hemodynamics of the above vessels, because the hemodynamic responses to the drug differed from individual to individual. The BFVI of the azygos vein correlated well with the azygos venous flow measured by the conventional thermodilution technique (r = 0.79, p less than 0.01). TE2DD appears to be a useful method for studying the hemodynamics of ascending collaterals in patients with portal hypertension.
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PMID:Effects of propranolol and nitroglycerin on cephalad collateral venous flow in patients with cirrhosis: evaluation using transesophageal real-time two-dimensional Doppler echography. 314 50

Propranolol, a non-selective beta-blocker, is known to decrease glucagon release in normal subjects. The present study was aimed at investigating the effects of propranolol on the hyperglucagonism commonly observed in patients with cirrhosis. Eight cirrhotic patients and 6 matched healthy controls were studied. The plasma concentrations of glucagon, insulin, c-peptide and glucose were measured in basal conditions and after stimulating glucagon secretion by an i.v. infusion of arginine (0.4 g/kg/30 min). The study was repeated 24 h later after inducing beta-blockade by the i.v. infusion of propranolol (10 mg). In baseline conditions, patients with cirrhosis, despite normal levels of insulin and glucose, had a marked hyperglucagonism (654 +/- 303 pg/ml vs. 269 +/- 90 in controls, P less than 0.01). Prior to propranolol, arginine infusion caused greater glucagon release in cirrhotics (71 +/- 31 ng.h.ml-1) than in controls (33 +/- 17 ng.h.ml-1, P less than 0.02), but despite a similar insulin secretion (assessed from c-peptide), blood glucose did not increase. After propranolol, glucagon secretion decreased as expected in controls (29 +/- 12 ng.h.ml-1, P less than 0.05) but experienced a paradoxical increase in cirrhotics (113 +/- 64 ng.h.ml-1, P less than 0.05). Again, despite the marked increase in glucagon release, there was no increase in glucose production, providing further evidence of the glucagon resistance that accompanies hyperglucagonism in cirrhosis. Our results suggest that hyperglucagonism with glucagon resistance might be the initial disturbance in carbohydrate metabolism in patients with cirrhosis. Contrary to what could be expected, propranolol does not correct but further accentuates this disturbance.
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PMID:Hyperglucagonism and glucagon resistance in cirrhosis. Paradoxical effect of propranolol on plasma glucagon levels. 339 82

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Under anesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension (portal venous pressure 15.3 +/- 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (-27%) and in cardiac index (-21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circulation.
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PMID:Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation. 348 14

In a prospective, randomized controlled trial, 53 patients with variceal hemorrhage from portal hypertension, including 44 with cirrhosis, were allocated, after initial control of the bleeding, to treatment by sclerotherapy alone, or by this together with oral propranolol in a dose sufficient to reduce resting pulse rate by 25% during the period up to the time when varices were obliterated. Eight of the 27 patients undergoing sclerotherapy alone rebled during this period as compared to 7 of the 26 patients in the additional propranolol group (p greater than 0.80), two patients from each group dying from uncontrollable variceal hemorrhage. Propranolol precipitated encephalopathy in one patient and complicated resuscitation following bleeding in a second, and as there was no evidence in this study that use of the drug reduced the frequency or severity of the variceal bleeding, its administration cannot be recommended during the period prior to obliteration of varices by sclerotherapy.
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PMID:Use of propranolol to reduce the rebleeding rate during injection sclerotherapy prior to variceal obliteration. 352 69

We conducted a prospective, randomized single-blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy-nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty-seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child-Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B, and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. beta-blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liver disease.
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PMID:Propranolol for the prevention of recurrent variceal hemorrhage: a controlled trial. 353 41

Patients with cirrhosis, who have survived an episode of variceal bleeding, often have far-advanced liver disease and therefore, on average, a severely restricted life expectancy. Still, the prognosis for the individual patient varies greatly depending on the presence or absence of large varices and the Child classification. Centres evaluating treatment of variceal bleeding often attract different patient populations. Comparison of the outcome of the complete series of patients is usually meaningless since results reflect the composition of the patient population rather than the applied therapy. The natural history of patients with variceal bleeding should be defined by Child category, allowing more precise definition of the therapeutic aims and subsequently assessment of the results. Persistent lowering of the portal pressure by pharmacological modulation of the portal haemodynamic system is now feasible due to the availability of long-acting oral medication. Propranolol is still the leading drug and, in one centre, its use in predominantly Child A patients was associated with a marked reduction in recurrent gastrointestinal bleeding and subsequently mortality rate. These results could not be reproduced in another centre. Both the restricted indication as well as the uncertain efficacy limit the current use of propranolol, but further pharmacological developments are bound to appear. Endoscopic sclerotherapy has become the treatment of choice in the prevention of recurrent variceal haemorrhage. The proponents of paravasal injection report excellent efficacy in combination with a low incidence of side-effects, whereas mainly theoretical reasons are advanced by users of intravariceal injections. Still, variceal haemorrhage remains an important clinical problem in the period between the start of sclerotherapy and the eradication of varices. Combination of sclerotherapy with portal antihypertensive medication might become the treatment of choice until eradication of varices has been achieved; thereafter either continued medication or repeated endoscopy will maintain an avariceal state and effective prevention of recurrent variceal bleeding.
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PMID:Prevention of recurrent variceal bleeding: non-surgical procedures. 388 14

The pharmacokinetic properties of propranolol and atenolol were evaluated both in 9 patients with cirrhosis and in 12 healthy subjects. The hemodynamic effects of the drugs were evaluated separately in the cirrhotic patients. Propranolol and atenolol significantly decreased wedged hepatic venous pressure and cardiac output in cirrhotic patients. Propranolol Cmax, tmax and AUC were significantly increased and plasma half-life was significantly prolonged in cirrhotic patients. In contrast, the corresponding pharmacokinetic values of atenolol were not significantly different in cirrhotic patients and in healthy subjects.
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PMID:Hemodynamic and pharmacokinetic study of propranolol and atenolol in cirrhosis patients. 404 73

Propranolol decreases portal venous pressure in patients with cirrhosis but no method is available in man to study the effect of this beta-blocker on splanchnic organ blood flow. Because in rats, the microsphere method allows evaluation of regional blood flow, the acute effect of propranolol on both splanchnic and systemic circulations was studied in normal rats and in rats with portal hypertension due to portal vein stenosis. Portal venous pressure significantly decreased during propranolol administration in normal (5.6 +/- 1.0-4.7 +/- 1.1 mm Hg; mean +/- SD) as well as in portal hypertensive rats (11.7 +/- 2.3-10.3 +/- 1.8 mm Hg). Propranolol slightly decreased cardiac output and arterial pressure in all rats. Portal tributary blood flow was significantly reduced by propranolol in normal rats (17.4 +/- 3.0-11.3 +/- 2.2 ml/min) and in portal hypertensive rats (23.7 +/- 5.0-16.6 +/- 3.3 ml/min). Accordingly vascular resistance of the different organs in the portal venous territory increased in these rats receiving propranolol. The percentage of the decrease in portal tributary blood flow was significantly more marked than the percentage of reduction in cardiac output in portal hypertensive rats but, in normal rats, these percentages were parallel. Hepatic arterial blood flow did not change or slightly increased and, consequently, hepatic arterial vascular resistance decreased. These findings further clarify the marked effects of propranolol on splanchnic circulation.
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PMID:Acute effect of propranolol on splanchnic circulation in normal and portal hypertensive rats. 405 47

Propranolol (20 mg 4 times a day) was given to patients with liver cirrhosis or fatty infiltration of the liver. In six patients with cirrhosis and a stable arterial plasma ammonia concentration before treatment, blood ammonia was increased significantly on day 3 of propranolol treatment. Arterial plasma ammonia concentration was still high on day 6 of propranolol. Individual percentage change in arterial ammonia ranged from 8% to 66%. After propranolol had been discontinued ammonia concentration returned to pretreatment concentrations in 3 to 6 days. In 3 patients with fatty livers and normal pretreatment ammonia concentrations no change was detected in arterial plasma ammonia while they were on propranolol.
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PMID:Propranolol increases arterial ammonia in liver cirrhosis. 612 60

The effects of different types of adrenoreceptor blocking agents on portal venous pressure were studied in patients with cirrhosis and portal hypertension. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta 1 and beta 2 blocker), and prazosin (alpha blocker) were compared in three groups of eight patients. Haemodynamic measurements were made before and after two or three and eight weeks of therapy. The dose of beta blockers was sufficient to reduce the exercise heart rate by more than 25%. Propranolol and prazosin produced a sustained reduction in the mean portohepatic venous pressure gradient of the order of 25% and 18% respectively. The cardiac index was significantly reduced by propranolol but not altered by prazosin. Atenolol produced an early reduction in portohepatic venous pressure which, although not sustained, showed a good correlation with reduction in cardiac index. No such relationship was found with propranolol. All three drugs were well tolerated by these patients with advanced cirrhosis. Therefore propranolol and prazosin have proved to be effective agents for the reduction of portal venous pressure.
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PMID:Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension. 636 Aug 15


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