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)

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propranolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis. 238 94

To elucidate the relationship between oxygen transport and uptake in cirrhosis, we studied the effects of three vasoactive drugs that change O2 transport. Systemic hemodynamics, blood gases and lactate concentration were measured in patients with alcoholic cirrhosis before and after intravenous dobutamine, propranolol and nitroglycerin. Nine patients received successively dobutamine and then propranolol. Ten patients received nitroglycerin. Three other patients without cirrhosis (controls) received dobutamine. In patients with cirrhosis, dobutamine infusion was accompanied by a significant increase in cardiac output (+21%), systemic O2 transport (+21%) and O2 uptake (+12%), whereas O2 extraction ratio and arterial lactate concentration did not change significantly. Propranolol administration was followed by a significant decrease in cardiac output (-24%) and systemic O2 transport (-25%) and a significant increase in O2 extraction ratio (+19%), whereas O2 uptake and arterial lactate concentration did not change. Nitroglycerin infusion was accompanied by a significant decrease in cardiac output (-21%), systemic O2 transport (-26%) and O2 uptake (-10%), whereas O2 extraction ratio (+18%) and arterial lactate concentration (+31%) significantly increased. In control patients, dobutamine infusion was accompanied by an increase in cardiac output and in systemic O2 transport and by a decrease in O2 extraction ratio, whereas O2 uptake was not modified. These results suggest that O2 uptake may be abnormally dependent on O2 transport in patients with cirrhosis.
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PMID:Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: effects of vasoactive drugs. 249 14

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.
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PMID:Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats. 258 90

A prospective, randomised, multicentre, single-blind comparison of propranolol with placebo in the primary prevention of upper gastrointestinal haemorrhage was conducted in 230 cirrhotic patients with large oesophageal varices. The dose of propranolol was progressively increased until resting heart rate was reduced by 20 to 25%. The final doses were 40 mg of conventional propranolol and 160 and 320 mg of long-acting propranolol daily in 22, 60 and 18% of patients, respectively. Patients who survived without bleeding were followed up for 436 +/- 172 days (mean +/- SD). After 2 years, the cumulative percentages of patients free from bleeding were 74% in the propranolol group and 39% in the placebo group (p less than 0.05). Similarly, cumulative 2-year survival was 72% in the propranolol group and 51% in the placebo group (p less than 0.05). Propranolol was well tolerated and only 13 patients were withdrawn from treatment. We concluded that propranolol treatment decreased the incidence of first bleeding and death during a period of 2 years in patients with cirrhosis and large esophageal varices.
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PMID:Propranolol in the primary prevention of upper gastrointestinal tract haemorrhage in patients with cirrhosis of the liver and oesophageal varices. 268 Apr 32

Propranolol is likely to be widely used to prevent variceal haemorrhage in patients with cirrhosis. Adverse reactions to propranolol in this group of patients are unusual, although the treatment group as a whole appears to tolerate drug therapy poorly. Therefore, compliance is likely to be a limiting factor, particularly in the prophylactic setting, and the use of once-daily long acting propranolol, which appears to be equally effective, has distinct advantages over the conventional, shorter acting formulation.
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PMID:Safety of propranolol in portal hypertension. Conventional and long acting formulations. 268 Apr 33

We studied the effects of a series of vasodilators on intrahepatic vascular resistance of isolated perfused cirrhotic rat livers in basal conditions and during norepinephrine-induced vasoconstriction. Cirrhosis was induced by repeated intraperitoneal injections of carbon tetrachloride. The vasodilators were a nonselective beta-adrenergic antagonist (propranolol), an alpha 1-adrenergic antagonist (prazosin), a nonselective beta-adrenergic agonist (isoproterenol), an alpha 2-agonist (clonidine), nitrovasodilators (nitroglycerin and nitroprusside), calcium channel blockers (verapamil, diltiazem, nifedipine), papaverine, diazoxide and pentoxifylline. In basal conditions, isoproterenol, nitroglycerin, papaverine, pentoxifylline and nitroprusside demonstrated significant vasodilatory activity. However, the response was weak and isoproterenol was the only drug active in the therapeutic range of concentrations. Propranolol, prazosin, verapamil, diltiazem, nifedipine and diazoxide were ineffective. Prazosin, papaverine and pentoxifylline reduced norepinephrine-induced vasoconstriction, whereas isoproterenol, clonidine and propranolol were ineffective. We conclude that several vasodilators can reduce resistance in the cirrhotic rat liver, but their potency is low and few are effective at therapeutic concentrations. Furthermore, their activity may be blunted when resistance is increased by norepinephrine.
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PMID:Effect of vasodilators on hepatic microcirculation in cirrhosis: a study in the isolated perfused rat liver. 271 34

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)
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PMID:Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis. 236 89

Propranolol, a beta-blocking agent, has been proposed in the prevention of gastro-intestinal bleeding in cirrhotic patients, and is known for its bronchoconstrictive effects. Since hypoxemia is a frequent finding in patients with cirrhosis, this work was undertaken to study the effects of intravenous propranolol on pulmonary function and on gas exchange in these patients. The 10 patients studied had cirrhosis associated with an increase in the alveolar arterial O2 difference, (A-a)DO2, an index of arterial oxygenation impairment. Their 1-s forced expiratory volume/forced vital capacity (FEV1/FVC) was normal, but in most a reduction of the forced expiratory flow of 25-75% of vital capacity was observed (FEF 25-75), suggestive of some degree of small airway obstruction. Although propranolol induced a significant decrease of FEF 25-75 from 67.7 +/- 19.3% to 55.4 +/- 21.5% (P less than 0.01), suggesting a bronchoconstriction of the small airways, there was no significant decrease in mean arterial oxygen partial pressure (PaO2) (74.1 +/- 6.4 mmHg before and 77.0 +/- 6.5 mmHg after propranolol). Indeed, a slight but significant improvement of the (A-a)DO2 was observed, from 39.1 +/- 5.9 mmHg to 34.4 +/- 4.9 mmHg (P less than 0.02). Although the mechanism of this beneficial effect remains to be elucidated, we conclude that in spite of its bronchoconstrictive action, propranolol is not contra-indicated in cirrhotic patients with hypoxemia who have normal expiratory flow.
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PMID:Effects of propranolol on pulmonary gas exchange in patients with cirrhosis. 280 64

Hepatic and respiratory failure, common complications following liver resection for hepatocellular carcinoma (HCC), especially when it is combined with liver cirrhosis, can be overcome by careful management of the circulatory and respiratory systems. Another common complication is intractable ascites which resists conventional therapy, such as, diuretics and protein replacement. Here we report a case in which intractable ascites was successfully treated with propranolol. The patient, a 48-year-old man who underwent liver resection for HCC combined with cirrhosis, started to suffer from ascites about 1 week after surgery. Upon administration of propranolol (1 mg/kg/day) with furosemide, his body weight decreased 500 g/day, returning to the preoperative value in 2 weeks in parallel with the normalization of the PRA. No side effects were observed during the medication period. Propranolol, a beta-adrenergic antagonist, is thought to suppress renin secretion from the juxtaglomerular apparatus in the kidney by blocking its beta-adrenergic receptor, thus suppressing the entire renin-angiotensin-aldosterone system. We concluded that propranolol is a promising drug for intractable ascites encountered with liver cirrhosis.
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PMID:[Effect of propranolol on intractable ascites following liver resection]. 287 20

To assess if propranolol prevents the first bleeding in cirrhosis, we randomly assigned 174 patients with large varices to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (oral vitamin K, 89 patients). Sixty-nine patients had alcoholic cirrhosis, 24 posthepatitis cirrhosis and 81 cryptogenic cirrhosis. At the time of inclusion, 75 patients (43%) had ascites and according to the Child-Pugh classification, 103 (59%) had Class A disease, 60 (34%) Class B and 11 (7%) Class C. We report here an interim analysis of the study when all patients had been followed for at least 1 year (mean follow-up = 22 months). At this time, the cumulative proportion of patients free of bleeding was 74% (both differences not significant), respectively. A retrospective analysis showed that the cumulative percentage of patients free of bleeding was significantly higher in the propranolol- than in the control-group in the subsets of patients without ascites or in Child-Pugh Class A: respectively, 87 vs. 64% (p = 0.023) and 88 vs. 64% (p = 0.01). No differences in bleeding incidence were found in patients with ascites or in Child-Pugh Class B or C. Propranolol treatment did not affect survival in any subgroup. Twenty-five patients had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 2). If confirmed on a longer follow-up, these results suggest that propranolol could prevent the first bleeding in patients with well-compensated cirrhosis.
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PMID:Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: a multicenter, randomized clinical trial. The Italian Multicenter Project for Propranolol in Prevention of Bleeding. 289 71


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