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Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

At least 271 records · Page 15Linked to original sources

Effect of propranolol on hepatic blood flow in patients with cirrhosis.

The effect of propranolol on systemic and hepatic hemodynamics was studied in patients with cirrhosis. One hour after 40 mg propranolol by mouth as well as during continuous oral dosing at doses that reduced heart rate 25%, cardiac output and the hepatic venous pressure gradient fell significantly, whereas arterial pressure and hepatic blood flow did not change significantly. In six patients with cirrhosis and surgical end-to-side portacaval shunts, cardiac output and the hepatic venous pressure gradient also decreased 15 minutes after intravenous propranolol (5 mg), whereas hepatic blood flow did not change significantly. In the patients with surgical shunts, systemic vascular resistance rose significantly but hepatic arterial vascular resistance fell. Our data show that in patients with cirrhosis, propranolol induces an increase in the fraction of cardiac output reaching the liver.

Administration, Oral↗

Effect of two models of portal hypertension on splanchnic organ blood flow in the rat.

Splanchnic organ blood flow and cardiac output were measured by the microsphere method in fasted rats with prehepatic portal hypertension due to portal vein stenosis, in rats with intrahepatic portal hypertension due to bile duct ligation, and in unoperated normal rats. Portal venous pressure was higher in both groups of portal hypertensive rats than in normal rats. Cardiac output was significantly higher in portal hypertensive rats than in normal rats. In rats with portal vein stenosis, splanchnic blood flow was higher than in controls. This increase was caused by increased perfusion of all organs drained by the portal vein, and by increased hepatic arterial blood flow. In rats with bile duct ligation, splanchnic blood flow was not significantly higher than in normal rats: haemoperfusion of all organs contributing to the portal circulation decreased, whereas hepatic arterial blood flow increased. As cardiac output rose similarly, the differences observed between the two types of portal hypertension depend mainly on the difference in distribution of flow within the splanchnic bed.

Animals↗

Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats.

To determine the effect of pentobarbital sodium anesthesia on the rat with portal hypertension due to portal vein stenosis, four groups of rats were studied. Cardiac output and regional blood flow were measured by radioactive microspheres in anesthetized and conscious sham-operated and portal-hypertensive rats. Anesthesia markedly decreased cardiac output in both sham-operated (109.7 +/- 4.6 vs. 77.8 +/- 1.4 ml/min, P less than 0.001) and portal-hypertensive rats (130.1 +/- 7.6 vs. 93.8 +/- 5.3 ml/min, P less than 0.01). In spite of this diminution in cardiac output, pentobarbital did not significantly change absolute blood flow values of splanchnic organs in either group. However, the fractions of cardiac output perfusing the splanchnic organs were significantly increased by pentobarbital in both groups because of the decrease in cardiac output: sham operated, anesthetized, 22.86 +/- 1.19% vs. conscious, 14.83 +/- 1.02%, P less than 0.001; and portal hypertensive, anesthetized, 26.67 +/- 0.71% vs. conscious, 19.07 +/- 1.44%, P less than 0.001. The hyperdynamic circulation of the portal vein-stenosed rat compared with the sham-operated rat continued to manifest itself with significantly increased portal pressure, cardiac output, and splanchnic blood flow, whether the animal was anesthetized or awake. We conclude that, despite marked hemodynamic changes induced by pentobarbital, the rat with portal vein stenosis remains a useful experimental model of portal hypertension.

Anesthesia, General↗

[Effects of glypressin on the splanchnic and systemic circulation in patients with cirrhosis].

Although not demonstrated in patients with cirrhosis, it is generally claimed that administration of vasopressin in the form of triglycyl-lysine-vasopressin (glypressin) may prevent untoward systemic effects of this former hormone. The aim of this study was to assess the effects of intravenous administration of 2 mg of glypressin on splanchnic and systemic hemodynamics in 9 patients with cirrhosis under stable circulatory conditions. One hour after the injection, the following statistically significant changes were observed as compared to the baseline values (m +/- SEM): wedged hepatic venous pressure, -9 +/- 2 p. 100; hepatic venous pressure gradient, -16 +/- 3 p. 100; azygos blood flow, -24 +/- 6 p. 100; heart rate, -16 +/- 3 p. 100; cardiac index, -23 +/- 2 p. 100; systemic vascular resistances, +47 +/- 11 p. 100; wedged pulmonary arterial pressure, +44 +/- 15 p. 100. In conclusion, in patients with cirrhosis in a stable hemodynamic condition, intravenous administration of glypressin decreased portal venous pressure and blood flow into the superior portal systemic collateral circulation but did not prevent the untoward systemic hemodynamic effects of vasopressin.

Adult↗

Hemodynamic and pharmacokinetic study of propranolol and atenolol in cirrhosis patients.

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.

Adult↗

Comparison of the short-term effects of mepindolol and propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis.

The splanchnic and systemic haemodynamic effects of mepindolol (0.6 mg, IV), a beta-blocker with a marked beta 2-blockade activity and propranolol (15 mg, IV) were studied in two groups of eight patients with portal hypertension due to cirrhosis. Similar decreases in the hepatic venous pressure gradient were observed after mepindolol and propranolol, whereas hepatic blood flow significantly decreased after mepindolol but did not significantly do so after propranolol. The decreases in cardiac output and heart rate were statistically significant and similar after mepindolol and propranolol. Mepindolol slightly decreased mean arterial pressure and propranolol slightly increased this pressure. Both beta-blockers significantly increased systemic vascular resistance. From these observations, it was not possible to demonstrate that mepindolol offered a beneficial effect on splanchnic haemodynamics in patients with portal hypertension due to cirrhosis.

Adult↗

Effects of propranolol on renal blood flow and renal function in patients with cirrhosis.

Systemic and splanchnic hemodynamics, renal blood flow, and renal function were studied in 13 patients with cirrhosis both before and 1 h after oral administration of 40 mg of propranolol (acute administration) and 1 mo after continuous administration of this substance at doses reducing the heart rate by 25% (chronic administration). Cardiac output and the gradient between wedged and free hepatic venous pressures significantly decreased after acute and chronic administration of propranolol; mean arterial pressure did not change significantly and systemic vascular resistance significantly increased. Renal blood flow and renal vascular resistance did not change significantly after acute administration of propranolol and renal function did not change significantly after acute or chronic administration of propranolol. We conclude that propranolol does not alter renal function in patients with cirrhosis who are in good physical condition.

Aldosterone↗

[Evaluation of the blood flow of superior portacaval anastomoses by the measurement of azygos blood flow in patients with alcoholic cirrhosis].

In patients with portal hypertension the azygos system collects the main part of superior portosystemic shunts; accordingly, azygos blood flow might be a reflection of this collateral circulation. Azygos blood flow, estimated by the continuous thermodilution method with a catheter inserted into the azygos arch, was measured in 20 patients with cirrhosis. The variability of baseline measurements was 6.9 +/- 3.0 p. 100 and the reproducibility was 5.7 +/- 5.8 p. 100. In patients with cirrhosis, azygos blood flow ranged from 0.22 to 1.25 l/min (0.64 /+- 0.30 l/min; mean +/- SD) and was significantly higher than in patients without portal hypertension (0.13 +/- 0.04 l/min). In this series of patients, azygos blood flow was significantly correlated with the hepatic venous pressure gradient but neither with hepatic blood flow nor with cardiac output. This study shows that azygos blood flow may be estimated with the continuous thermodilution method and that azygos blood flow is approximately six times higher in cirrhotic patients than in controls. This result suggests that blood flow through the superior portosystemic shunts is very high.

Azygos Vein↗

Discrepancy between wedged hepatic venous pressure and portal venous pressure after acute propranolol administration in patients with alcoholic cirrhosis.

In patients with alcoholic cirrhosis, wedged hepatic venous pressure closely reflects portal venous pressure. This study was carried out to determine if propranolol-induced reductions in portal venous pressure are accurately evaluated by the measurement of wedged hepatic venous pressure. Hepatic venous cannulation and percutaneous transhepatic catheterization of the portal vein were simultaneously performed in 7 patients with alcoholic cirrhosis. One hour after oral administration of 40 mg of propranolol, wedged hepatic and portal venous pressures significantly decreased from 24.3 +/- 3.5 (mean +/- SD) to 19.0 +/- 3.0 mmHg, and from 24.7 +/- 3.9 to 22.4 +/- 3.6 mmHg, respectively. Although no significant difference was found between baseline wedged hepatic and portal venous pressures, a significant difference was found between these pressures after propranolol administration. We concluded that during acute administration of a drug acting on the splanchnic circulation, the measurement of wedged hepatic venous pressure may not provide a reliable estimation of the magnitude of the changes in portal venous pressure. There is, however, no evidence that the direction of the changes might not be adequately assessed by wedged hepatic venous pressure measurement.

Aged↗

[Systemic circulatory hyperkinetic syndrome in patients with cirrhosis. Relation with hepatocellular failure and portal hypertension].

Hyperkinetic circulatory state is common in patients with cirrhosis but the cause of this syndrome has not been clearly elucidated. Systemic hemodynamic changes and their relationship to liver failure and splanchnic hemodynamics were studied in 100 patients with cirrhosis and were compared to a group of 15 patients without portal hypertension. Cardiac output was significantly higher and systemic vascular resistance was significantly lower in cirrhotic patients than in control patients. Multivariate analysis revealed that among different clinical, biochemical and splanchnic hemodynamic data, serum albumin, serum bilirubin, plasma prothrombin, and gastrointestinal bleeding significantly and independently explained the variation of cardiac output and systemic vascular resistance. No relationship was found between hepatic venous pressures or the presence of ascites and the hyperkinetic syndrome. From these results, it is concluded that in patients with cirrhosis liver failure is partly responsible for the hyperkinetic state.

Adult↗

[Hepatic biopsy by transvenous approach in hemopathies with coagulation disorders].

Percutaneous liver biopsy is often contra-indicated in patients with blood diseases associated with disorders of coagulation. Transvenous liver biopsy was performed in 36 such patients who also presented with unexplained hepatic abnormalities. In 31 patients liver tissue sampling was sufficient for adequate evaluation of liver damage: malignant infiltration was confirmed in 21, and associated hepatic disorder was diagnosed in 10. Five patients had a histologically normal liver. This study shows that in patients with blood disease enough liver tissue can be obtained by transvenous biopsy for a diagnosis to be made.

Biopsy↗

Hemodynamic effects of dobutamine in patients with alcoholic cirrhosis.

The effects of dobutamine infusion on cardiac output, hepatic blood flow, and the gradient between wedged and free hepatic venous pressures were studied in 14 patients with alcoholic cirrhosis. Cardiac output rose from 5.8 +/- 1.2 l/min (mean +/- SD) to 7.1 +/- 1.5 l/min. Hepatic blood flow and the gradient between wedged and free hepatic venous pressures did not change significantly during the dobutamine infusion (1.360 +/- 0.510 l/min to 1.446 +/- 0.502 l/min and 17.7 +/- 4.9 mm Hg to 17.9 +/- 3.7 mm Hg). We conclude that in alcoholic cirrhotic patients, dobutamine increased cardiac output as a result of increased heart rate and that there were no significant changes in percentage of cardiac output distributed to the liver.

Catecholamines↗

Propranolol does not further decrease the clearance of antipyrine in patients with alcoholic cirrhosis.

We determined the clearance of antipyrine before, and during, the administration of propranolol in eight male patients with alcoholic cirrhosis and a recent episode of gastrointestinal bleeding. The clearance of antipyrine in these patients was markedly reduced as compared with that in eight male, age-matched control subjects but was not further decreased after 1 month of propranolol administration. Antipyrine is the prototype of a drug with a low hepatic clearance. We suggest that the hepatic metabolism of some low clearance drugs may not be further decreased when patients with alcoholic cirrhosis are placed on propranolol therapy for the prevention of recurrent gastrointestinal bleeding.

Adult↗