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)

It has been postulated that the adverse metabolic effects of beta-adrenergic blockade with propranolol in cirrhosis may be related to altered delivery and utilisation of oxygen, particularly in patients with advanced alcoholic liver disease (ALD). Consequently, in 10 patients with decompensated ALD, we assessed (a) systemic and hepatic oxygen delivery (DO2), extraction ratio (%O2E) and consumption (VO2), (b) myocardial VO2 (assessed by the rate-pressure product [RPP], together with full systemic and splanchnic haemodynamics) and (c) hepatic redox state (HRS), measured indirectly by the arterial ketone body ratio (KBR i.e. ratio of acetoacetate/beta-hydroxybutyrate), prior to and following intravenous propranolol (0.1-2 mg/kg). Results are expressed as mean +/- S.E.M. Propranolol reduced DO2 (700 +/- 33 vs. 583 +/- 32 ml/min/m2, p < 0.05) and myocardial VO2 (RPP 72 vs. 58, p < 0.05). The %O2E increased however, (18.5 +/- 1.3 vs. 22.6 +/- 1.6%, p < 0.05), resulting in unaltered systemic VO2 (127 +/- 7.3 vs. 131 +/- 6.9 ml/min/m2, p > 0.10). Similarly hepatic VO2 did not change. KBR was not altered (0.44 +/- 0.08 vs. 0.48 +/- 0.07), and in fact improved in two patients (Child C12 and C13) from 0.17 to 0.34 and 0.12 to 0.27, respectively. In conclusion, the results of this study suggest that an underlying O2 debt exists in patients with advanced alcoholic cirrhosis and that beta-adrenergic blockade with propranolol 'normalises' the O2 supply-consumption relationship resulting in more efficient O2 utilisation without adversely affecting HRS. The mechanism of this action may be related to the antagonism of beta 2-mediated arteriovenous shunting resulting in appropriate blood redistribution.
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PMID:Metabolic effects of beta-adrenergic receptor blockade in advanced alcoholic cirrhosis. 838 56

This study investigated the effects of the short-term administration of propranolol on gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy. Portal hypertensive gastropathy is a common cause of nonvariceal bleeding in cirrhosis, which is associated with increased gastric mucosal perfusion and is favorably influenced by propranolol therapy. Gastric mucosal perfusion was evaluated with laser-Doppler flowmetry and reflectance spectrophotometry. Measurements were performed under basal conditions and after the double-blind administration of propranolol (0.15 mg/kg intravenously) or placebo. Propranolol administration significantly reduced (p < 0.001) the laser-Doppler signal (2.93 +/- 0.23 vs. 2.25 +/- 0.22 V) and the hemoglobin content of the gastric mucosa (99.2 +/- 3.8 vs. 89.3 +/- 3.1 arbitrary units), whereas the oxygen content remained unchanged (37.4 +/- 1.2 vs. 36.9 +/- 1.0 arbitrary units). Placebo administration had no effect in any of these parameters. Changes in gastric perfusion after propranolol administration were associated with a significant decrease in hepatic venous pressure gradient and azygos blood flow. We conclude that short-term propranolol administration, in addition to lowering portal pressure, reduces the increased gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy, an effect that may contribute to prevention of bleeding from these lesions.
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PMID:Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy. 842 18

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.
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PMID:Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis. 873 82

A nocturnal increase in portal pressure and blood flow was demonstrated in patients with cirrhosis, suggesting that these hemodynamic changes may contribute to the triggering of the hemorrhagic episodes observed during the night in these patients. It is known that propranolol reduces portal flow, thus reducing the risk of variceal bleeding. In a double-blind, placebo-controlled study, we evaluated the effect of long-term propranolol administration on the daily fluctuation of systemic and splanchnic hemodynamic parameters in 14 patients with cirrhosis. Cardiac output and portal blood flow were measured by the Doppler technique. A daily fluctuation of both cardiac output and portal blood flow was observed, peaking at midnight. beta-Adrenergic blockade was manifested by a significant reduction in heart rate (-21% +/- 4%, P < .01) and cardiac output (-12% +/- 2%, P < .05). A significant decrease in portal blood flow (-20% +/- 4%, P < .01) was also observed in these patients. Propranolol administration blunted the time-related changes in cardiac output and portal blood flow. In contrast, patients receiving placebo had a nocturnal peak of both parameters similar to that observed under basal conditions. Our study shows that chronic propranolol administration abolishes the nocturnal peak of portal blood flow in patients with cirrhosis and indicates a preventive effect of propranolol in these patients.
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PMID:Daily variation in portal blood flow and the effect of propranolol administration in a randomized study of patients with cirrhosis. 904 96

Propranolol, a beta-adrenergic blocking agent commonly used in the treatment of hypertension, decreases mesenteric blood flow during exercise, at rest, and in cirrhosis. Widespread idiopathic myointimal hyperplasia of mesenteric veins produces intestinal ischemia in otherwise healthy individuals. This report describes a 42-year-old woman who died suddenly and unexpectedly while attending a ball game. She had hypertension treated with propranolol and no other clinically apparent disorders. Autopsy revealed mild mesenteric venous myointimal hyperplasia and segmental jejunal infarction. Recent clinical and experimental studies are used to propose possible mechanisms for this death which combine the effects of propranolol and mesenteric venous myointimal hyperplasia.
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PMID:Unexpected sudden death during propranolol therapy in a patient with mild mesenteric venous myointimal hyperplasia. 967 May 18

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 </=12 mm Hg in a greater proportion of patients (64% vs. 14%, P <.05). Both drugs caused similar reductions in hepatic and azygos blood flows, suggesting that the greater HVPG decrease by carvedilol was because of reduced hepatic and portocollateral resistance. Propranolol caused greater reductions in heart rate and cardiac output than carvedilol, whereas carvedilol caused a greater decrease in mean arterial pressure (-23.1 vs. -11%, P <.05). Thus, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis, suggesting a greater therapeutic potential. However, it causes arterial hypotension, which calls for careful evaluation before its long-term use.
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PMID:Carvedilol, a new nonselective beta-blocker with intrinsic anti- Alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis. 1072 17

Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with beta-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of (99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA]), and transit (geometric center ratio of (51)Cr) were assessed in 29 rats with carbon tetrachloride (CCl(4)) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a (99m)Tc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a (99m)Tc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation.
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PMID:Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites. 1061 26

Variceal bleeding due to portal hypertension is a frequent and severe complication of cirrhosis in children as in adults. The prophylactic approach is important for these high mortality bleedings, both for the first and for recurrent attacks. Variceal bleeding/rebleeding rates were evaluated in sixty patients with cirrhosis who received 1-2 mg/kg/day propranolol p.o. for 1-14 years. According to Child-Pugh classification, 33 patients were Class A, 22 Class B, and five Class C. Patients were divided into two groups according to whether they had variceal bleeding before starting propranolol treatment (secondary prevention; 15 patients) or not (primary prevention; 45 patients). Seven (15.6%) of 45 patients experienced bleeding on propranolol therapy in the primary prevention group, while eight (53.3%) of 15 patients bled in the secondary prevention group (p < 0.01). Propranolol was found effective in primary and secondary prevention in Class A patients, while it was effective only for primary prevention in Class B and C patients. Propranolol administration is useful for preventing first and recurrent variceal bleeding in Class A cirrhotic patients. In Class B and C cirrhotic patients, it is effective only for preventing the first bleeding episode.
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PMID:Propranolol for primary and secondary prophylaxis of variceal bleeding in children with cirrhosis. 1073 66

In patients with cirrhosis of liver, variceal bleeding is the most serious complication, with a mortality of up to 50%. Primary prophylaxis of variceal bleeding with shunt surgery or endoscopic variceal sclerotherapy was attempted and then abandoned, as higher rates of complications and mortality were observed. Endoscopic variceal ligation is now being recommended for primary prophylaxis in some centers, as it has fewer complications than sclerotherapy. But this has been done with inadequate evaluation of the cost-effectiveness of variceal ligation. Propranolol therapy is also being widely used for a selected group of patients (large varices with cherry red spots), despite its several limitations and side effects, to reduce frequency of bleeding but without improving survival. Is primary prophylaxis of variceal bleeding cost-effective? The cost involved needs to be accurately assessed in different countries.
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PMID:Primary prophylaxis of variceal bleeding in liver cirrhosis: failure to learn from past experience. 1167 40

Portal hypertension is a dramatic complication in liver cirrhosis by efraction of the varices localized more frequently in the esophagus. It has been an actual subject due to physiopathological research (endotelin system, nitric system etc), diagnosis (echoendoscopy, color Doppler), and therapeutically progress. Propranolol, available at a low cost, is efficient and unanimously accepted in the prophylactic treatment of medium and large varices which have never bled as well as in the hemorrhage due to variceal efraction which stopped therapeutically or spontaneously. This drug diminishes the risk of rebleeding. Besides the pharmacological treatment, terlipresine, octreotid, sclerotherapy and bandlegation are used in active hemorrhage due to variceal efraction. If this fails other methods for haemostasis are used: portosystemic transjugular shunt, mechanical tamponade, selective surgery and ideally hepatic transplant. Except for the hepatic transplant, none of the mentioned methods can improve the rate of survival in-patients, which depends on the state of the hepatic failure.
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PMID:[Portal hypertension in liver cirrhosis]. 1209 60


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