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Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

At least 217 records · Page 12Linked to original sources
PubMed1989

Effects of oxygen inhalation on tissue oxygenation in patients with cirrhosis. Evidence for an impaired arterial baroreflex control.

In patients with cirrhosis, O2 uptake, i.e., O2 consumption, is abnormally decreased. We administered 50% O2 for 30 min in eight patients with alcoholic cirrhosis to determine whether the subsequent increase in arterial O2 content may correct the low O2 consumption. In addition, we studied in these patients the reflex control of cardiac output and blood pressure by arterial baroreceptors, as O2 inhalation induces a systemic vasoconstriction. Arterial O2 tension, oxyhaemoglobin saturation and arterial O2 content significantly increased as well as systemic vascular resistance and arterial pressure. In contrast, O2 consumption (which was below normal values) under basal conditions, O2 transport, O2 extraction ratio, heart rate, right atrial and pulmonary wedged pressures, cardiac output, hepatic venous pressures, hepatic and azygos blood flows were unaffected by O2 administration. In three patients receiving air, no significant change was observed. Our results show that, in patients with cirrhosis, inhalation of 50% O2 does not correct O2 consumption. We may conclude that reflex control of cardiac output and arterial pressure by arterial baroreceptors is impaired in these patients.

Blood Pressure↗
PubMed1989

Reduction of portal pressure by acute administration of furosemide in patients with alcoholic cirrhosis.

In patients with cirrhosis, it has been demonstrated that blood volume and degree of portal hypertension are correlated. Hence, a reduction of blood volume by furosemide could decrease portal pressure and could thereby be useful in the treatment of portal hypertension. Splanchnic and systemic haemodynamics were evaluated before and 1 h after intravenous administration of furosemide (0.75 mg/kg) in 10 patients with cirrhosis. Furosemide significantly increased haemoglobin from 12.4 to 13.0 g/dl and patients passed more than 1 l of urine within the 3 h following furosemide administration. These findings confirm that blood volume decreased after diuretic administration. Cardiac output significantly decreased from 6.6 +/- 2.3 to 5.5 +/- 2.2 l/min, while arterial pressure and heart rate did not change significantly. Furosemide significantly decreased wedged hepatic venous pressure from 31.1 +/- 6.2 to 27.7 +/- 5.2 mmHg, but not free hepatic venous pressure. Accordingly, the hepatic venous pressure gradient significantly decreased from 22.1 +/- 5.4 to 19.5 +/- 4.0 mmHg. Azygos blood flow and hepatic blood flow also significantly decreased from 0.40 +/- 0.17 to 0.31 +/- 0.13 l/min and from 1.49 +/- 0.50 to 0.82 +/- 0.30 l/min, respectively. These results show that diuretic therapy markedly influences splanchnic haemodynamics.

Adult↗
PubMed1989

Effects of glucagon on systemic and splanchnic circulation in conscious rats with biliary cirrhosis.

To elucidate the relationship between the haemodynamic changes and glucagon in cirrhosis, we infused physiologic and supraphysiologic doses of this hormone in conscious rats with portal hypertension due to biliary cirrhosis. Cardiac output and splanchnic organ blood flows were measured by the radioactive microsphere method before and 30 min after glucagon infusion at doses of 2, 5 and 10 ng/min. Serum glucagon increased from a basal level of 92 +/- 17 pg/ml (mean +/- S.E.) to 399 +/- 89, 1151 +/- 136 and 2064 +/- 328 pg/ml, respectively, in sham-operated rats, and from 743 +/- 75 pg/ml to 1497 +/- 197, 1583 +/- 356 and 2957 +/- 649 pg/ml, respectively, in cirrhotic animals at 2, 5 and 10 ng/min doses. In both groups, cardiac output did not change after glucagon infusion at 2 and 5 ng/min doses, suggesting that factors other than glucagon are primarily responsible for the systemic hyperdynamic circulation in cirrhosis. Portal tributary blood flow increased significantly after glucagon infusion in sham-operated rats by 34 and 65% at doses of 5 ng/ml and 10 ng/ml, respectively, and in cirrhotic rats by 29% at a dose of 10 ng/ml. However, portal tributary blood flow did not change after glucagon infusion at the physiologic dose of 2 ng/min. This study shows that glucagon infused at a physiologic dose does not increase splanchnic blood flow, although it increases portal tributary blood flow at supraphysiologic doses. The discrepancy between blood glucagon levels and splanchnic haemodynamic responses suggests that glucagon plays only a minor role and that other factors are primarily responsible for the hyperdynamic state of the splanchnic circulation in rats with biliary cirrhosis.

Animals↗
PubMed1989

Hyperkinetic circulatory syndrome in patients with presinusoidal portal hypertension. Effect of propranolol.

This study evaluates systemic and splanchnic haemodynamics and the effect of propranolol in 15 patients with presinusoidal portal hypertension (portal vein obstruction, n = 11; schistosomiasis, n = 4). These patients exhibited a hyperkinetic circulatory syndrome characterized by high cardiac index (4.4 +/- 1.61.min-1.m-2, mean +/- S.D.) and by low systemic vascular resistance despite normal liver function and sinusoidal pressure. Hepatic blood flow was decreased in half of the patients with portal vein obstruction. Azygos blood flow, an estimate of superior portal-systemic collateral circulation, was markedly increased in all patients (0.46 +/- 0.19 l/min, upper limit of normal: 0.19 l/min). Therefore, in these patients with normal hepatic venous pressure gradient, azygos blood flow measurement provides an index of splanchnic haemodynamic changes. Propranolol administration (15 mg, i.v.) reduced the hyperkinetic circulatory syndrome, with a significant decrease in heart rate (-17 +/- 6%), cardiac index (-25 +/- 12%) and azygos blood flow (-40 +/- 26%) and a significant increase in systemic vascular resistance (+40 +/- 40%). These results suggest that the hyperkinetic circulatory syndrome observed in these patients, could be related to an increase in beta-adrenergic activity. The decrease in azygos blood flow, after propranolol administration, was significantly correlated (r = 0.94) with the increase in right atrial pressure. This finding suggests that propranolol may act through an increase in portal-systemic collateral venous tone. These haemodynamic results justify, in patients with presinusoidal portal hypertension, clinical trials investigating the beneficial effect of beta-blockers on gastrointestinal bleeding caused by portal hypertension.

Adult↗
PubMed1989

Somatostatin analogue improves survival in conscious cirrhotic rats subjected to gastrointestinal bleeding.

1. The continuing doubt concerning the value of vasoconstrictive therapy for gastrointestinal bleeding may be related to the complexity of clinical trials in such a situation. 2. The effect of SM 201-995, a somatostatin analogue, was investigated in conscious cirrhotic rats before, during and after experimental bleeding from the portal territory. 3. Before haemorrhage, somatostatin analogue (8 micrograms h-1 kg-1 body weight, intravenously) produced a significant decrease in portal pressure (17%), whereas a placebo (saline) lacked significant effect. 4. The rats were then subjected to spontaneous bleeding, by disconnection of the portal catheter from the pressure gauge, for a 5 min period. At the end of the haemorrhage, haemodynamic parameters did not significantly differ between the group receiving somatostatin analogue and that receiving placebo. 5. Fifteen minutes after the end of the bleeding period, portal pressure was significantly lower in rats receiving somatostatin analogue [8.5 +/- 0.5 mmHg (1.13 +/- 0.07 kPa), mean +/- SEM] than in rats receiving placebo [11.0 +/- 1.1 mmHg (1.50 +/- 0.15 kPa)]. 6. The volume of blood lost and mortality were significantly lower in the group treated with somatostatin analogue (2.3 +/- 0.1 ml/100 g body weight and 8%, respectively) than in the group receiving placebo (3.0 +/- 0.1 ml/100 g body weight and 50%, respectively). 7. These results demonstrate, in an experimental model, the beneficial effect of somatostatin analogue for the treatment of gastrointestinal bleeding due to portal hypertension. They suggest that administration of this substance should be started as soon as possible after the beginning of haemorrhage and continued after the cessation of bleeding.

Animals↗
PubMed1989

Hemodynamic effects of a combination of clonidine and propranolol in conscious cirrhotic rats.

The hemodynamic effects of the combination of clonidine and propranolol were studied in conscious rats with portal hypertension owing to secondary biliary cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed in three groups of eight rats before and after drug administration. The combined effects of clonidine (2 micrograms/100 g body wt., i.v.) and propranolol (0.2 mg/min for 10 min) were compared with those observed after administration of either clonidine alone or propranolol alone. The association of clonidine and propranolol induced significant decreases in portal pressure (30%) and portal tributary blood flow (43%), the magnitude of these changes being significantly more marked than that after administration of either clonidine alone (12 and 20%, respectively) or propranolol alone (16 and 17%, respectively). After the combination, no significant change in arterial pressure was observed, but cardiac output significantly decreased and systemic vascular resistance significantly increased. Renal blood flow decreased to a similar extent (40%) in the three groups. These findings indicate that the combination of clonidine and propranolol is more effective for reversing splanchnic hemodynamic changes than clonidine alone or propranolol alone. The additive effects of this association are in agreement with the action of clonidine and propranolol at different levels (central and peripheral) and on different receptors (alpha and beta). It suggests that an increase in sympathetic activity may play a major role in hemodynamic changes observed in experimental cirrhosis.

Animals↗
PubMed1989

A randomised controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis.

74 cirrhotic patients with a history of variceal or gastric bleeding were randomly assigned to treatment with propranolol (40 to 360 mg/day) or placebo. The patients were all in good condition and doses of propranolol were titrated until a 25% reduction in heart rate was achieved. After 2 years, the cumulative percentage of patients free from rebleeding was significantly greater among the patients receiving propranolol (79%) than in the placebo group (32%; p less than 0.0001). Similarly, the percentage of surviving patients was significantly greater with propranolol (90%) than with placebo (57%; p less than 0.02) after 2 years. It was concluded that in cirrhotic patients in good condition, propranolol reduced both the risk of recurrent gastrointestinal haemorrhage and the mortality rate during a 2-year period of continuous administration of the drug.

Adult↗
PubMed1989

[Tissue hypoxia and hepatocellular insufficiency in patients with cirrhosis].

To determine whether tissue hypoxia occurred in cirrhosis, oxygen contents, mixed venous and hepatic venous lactate concentrations as well as systemic hemodynamics were studied in 53 patients with cirrhosis. The influence of liver failure on tissue oxygenation was also studied. Cardiac index and mixed venous and hepatic venous lactate concentrations were significantly higher in patients with cirrhosis than in 20 control subjects. Oxygen consumption, oxygen extraction ratio and mixed venous and hepatic venous carbon dioxide tensions were significantly lower in the former than in the latter. Oxygen transport was not significantly different between the two groups. Cardiac index and oxygen transport were not significantly different between grade A (Pugh's classification) and grade C patients. Mixed venous as well as hepatic venous lactate concentrations were significantly higher while oxygen consumption, oxygen extraction ratio and carbon dioxide tensions were significantly lower in grade C than in grade A patients. We conclude that tissue hypoxia occurs in patients with cirrhosis and hepatic insufficiency. This tissue hypoxia might be due to arteriovenous shunting-related limitation of tissue oxygen extraction.

Adult↗
PubMed1989

[Influence of ascites on splanchnic and systemic hemodynamics in patients with alcoholic cirrhosis].

The effect of ascites on splanchnic and systemic hemodynamics was retrospectively studied in 256 patients with alcoholic cirrhosis. The patients were divided into 3 classes: no ascites, moderate ascites, and large ascites. They were also classed into 3 groups according to a modified Pugh classification (ascites was not taken into account). In patients without ascites, cardiac output was positively related to the severity of liver disease. This result was not found in patients with large ascites. Similarly, in patients with no or moderate ascites, the degree of portal hypertension estimated by the hepatic venous pressure gradient was associated with liver failure. In patients with large ascites, hepatic venous pressure gradient was higher than in patients without ascites but this relation was observed only in patients without liver failure. These results show that ascites reduces the relation between cardiac output and liver failure and increases the degree of portal hypertension but not cardiac output.

Ascites↗
PubMed1988

Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension.

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.

Animals↗
PubMed1988

Liver phospholipidosis induced by parenteral nutrition: histologic, histochemical, and ultrastructural investigations.

Histochemical and electron microscopic examinations of the liver were performed in 5 adults receiving parenteral nutrition for greater than 18 mo and in 4 adults receiving parenteral nutrition for less than 5 mo. Phospholipidosis, reflected by the presence of cytoplasmic phospholipid deposits at histochemical examination and the presence of multilamellar lysosomes at electron microscopy, was marked and present in hepatocytes, Kupffer cells, and portal macrophages in all 5 patients receiving parenteral nutrition for greater than 18 mo. Mild phospholipidosis, affecting only hepatocytes, was demonstrated in 3 of the 4 patients receiving parenteral nutrition for less than 5 mo. These findings indicate that liver phospholipidosis is relatively common in patients receiving parenteral nutrition and that the degree of liver phospholipidosis depends on the duration of parenteral nutrition. Liver phospholipidosis might be due to intrahepatic accumulation of intravenous phospholipids provided by fat-emulsion sources.

Adult↗
PubMed1988

Chronic Q fever hepatitis complicated by extensive fibrosis.

Liver involvement is common in acute and chronic Q fever and consists of nonspecific hepatitis and granulomas without fibrosis. We report the case of a patient suffering from chronic Q fever with nonspecific hepatitis and granulomas, in whom progressive development of extensive liver fibrosis was documented by repeated biopsies.

Aged↗
PubMed1988

Liver hypermetabolism during alcohol withdrawal in humans. Role of sympathetic overactivity.

Catecholamines, which are elevated during alcohol withdrawal, can alter hepatic blood flow and increase hepatic oxygen consumption. We hypothesized that, in the withdrawal state, hepatic oxygen consumption and delivery could be altered in relation to an increased sympathetic activity. Thirteen chronic alcoholics were studied 34-72 h after withdrawal and 10 days later (control period) using conventional hemodynamic methods. As compared with the control period, splanchnic oxygen uptake was elevated at withdrawal (74.5 +/- 27.1 vs. 59.2 +/- 16.8 ml/min, p less than 0.025) and its variation was correlated with that of plasma epinephrine (r = 0.70, p less than 0.01). The hepatic venous oxygen content was reduced at withdrawal (113 +/- 22 vs. 126 +/- 21 ml/L, p less than 0.025) and correlated inversely with plasma norepinephrine levels (r = 0.56, p less than 0.01). We conclude that, during alcohol withdrawal in humans, hepatic energy expenditure may be elevated in relation to epinephrine secretion and that sympathetic overactivity may hinder the adaptive response in hepatic blood flow. The wide range in sympathetic nervous response to alcohol withdrawal could explain some differences in individual susceptibility to liver damage caused by alcohol.

Energy Metabolism↗