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Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

342 records · Page 19Linked to original sources
PubMedDate not supplied

Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis.

A decrease in plasma noradrenaline--a reflection of sympathetic nervous system activity--by clonidine, a centrally acting alpha 2-agonist, could reduce the hyperdynamic circulation observed in cirrhosis and may thereby decrease portal hypertension. Plasma noradrenaline concentration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after administration of either 150 micrograms of clonidine or placebo. Plasma noradrenaline concentration significantly decreased in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (-17.4%), mean arterial pressure (-12.2%), hepatic venous pressure gradient (-19.7%) and azygos blood flow (-26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and changes in systemic or splanchnic hemodynamics. Hepatic blood flow was not changed by clonidine. Placebo administration had no effect on any laboratory or hemodynamic measurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation suggests that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.

Aged↗
PubMedDate not supplied

Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding.

In a previous randomized trial, we demonstrated that propranolol prevented recurrent gastrointestinal bleeding in patients with cirrhosis. We have undertaken the present study in a new group of patients to ascertain the factors associated with rebleeding. Among 232 patients with cirrhosis admitted for gastrointestinal bleeding, 127 were included. They received propranolol orally at a dose reducing the heart rate by 25%. The median follow-up period was 682 days. The following factors were studied: cause of cirrhosis; severity of cirrhosis; hepatocellular carcinoma recognized after inclusion; compliance; persistent decrease in heart rate; dose of propranolol; alcohol abstinence; previous history of hemorrhage; time interval from hemorrhage to onset of propranolol administration, and source of bleeding. The percentage of patients free of rebleeding was 71% at 1 year and 57% at 2 years. Only five factors were significantly and independently associated with rebleeding: occurrence of hepatocellular carcinoma; lack of compliance; lack of persistent decrease in heart rate; lack of abstinence, and previous history of bleeding. In conclusion, this study confirms the results of our previous trial and suggests that certain factors play a role in the mechanism of rebleeding in patients receiving propranolol.

Adult↗
PubMedDate not supplied

Beneficial hemodynamic effects of ketanserin in patients with cirrhosis: possible role of serotonergic mechanisms in portal hypertension.

We studied the acute effects of ketanserin, a serotonin S2 antagonist, on systemic and splanchnic hemodynamics in 11 patients with cirrhosis. Mean arterial pressure decreased moderately but significantly after ketanserin. This effect was maximal at 5 min and correlated to the severity of cirrhosis. Cardiac index and systemic vascular resistance were not significantly changed. The hepatic venous pressure gradient, used as an index of portal pressure, significantly decreased after ketanserin (-23%). Azygos blood flow, a reflection of superior portosystemic collateral blood flow, also significantly decreased (-26%), but this effect was delayed, progressive and not correlated to the arterial pressure decrease. Hepatic blood flow was unchanged. These findings suggest that the systemic and splanchnic circulations may be hypersensitive to ketanserin in cirrhotic patients, and that serotonergic mechanisms may contribute to maintain portal hypertension. New specific antiserotonergic drugs deserve further evaluation for potential therapeutic implications in portal hypertension.

Azygos Vein↗
PubMedDate not supplied

Lack of vasopressin action on splanchnic hemodynamics during bleeding: a study in conscious, portal hypertensive rats.

Due to the marked effects of hemorrhage on cardiac output and splanchnic hemodynamics, the circulatory actions of vasopressin may differ during bleeding as opposed to stable conditions. We evaluated this hypothesis in conscious rats with portal hypertension due to chronic portal vein stenosis, by comparing the effects of a vasopressin infusion (0.02 IU per kg per min) to those of a control saline infusion, during and after a hypotensive hemorrhage (25 ml per kg). We also studied unbled portal hypertensive rats receiving an identical infusion of vasopressin or saline. During and after hemorrhage, vasopressin induced significant changes in systemic hemodynamics but had no effect on portal pressure, portal tributary blood flow and nonhepatic splanchnic arteriolar resistance. In unbled animals, by contrast, vasopressin decreased portal pressure and portal tributary blood flow and increased nonhepatic splanchnic arteriolar resistance. Our data further indicate that hemorrhage alone caused an early vasoconstriction in the portal tributaries and a delayed vasoconstriction in the nonsplanchnic vascular bed while vasopressin during hemorrhage induced an early and sustained vasoconstriction in the nonsplanchnic vascular bed as well as in the portal tributaries. The results show that, during and after severe bleeding, vasopressin exerts little influence on portal hemodynamics. Although these data do not allow firm conclusions concerning the therapeutic efficacy of vasopressin in bleeding esophageal varices, they demonstrate that the splanchnic actions of vasoactive substances cannot be readily extrapolated from stable conditions to hemorrhage.

Animals↗
PubMedDate not supplied

Systemic and splanchnic hemodynamic effects of intravenous hypertonic glucose in patients with cirrhosis.

In animals, there may exist a hyperemic response in the portal circulation during intravenous administration of hypertonic glucose, but a hemodynamic response of this kind has never been described in man. This study was designed to evaluate if hyperglycemia itself could induce systemic or splanchnic hemodynamic changes in patients with cirrhosis. Sixteen patients with cirrhosis were studied before and during i.v. infusions of hypertonic (900 mOsmoles per liter) glucose (n = 8), mannitol (n = 4) or saline (n = 4) at 2 ml per min. In the group receiving glucose, there were significant increases in hepatic venous pressure gradient (+12%), azygos blood flow (+27%) and pulmonary capillary pressure (+32%), while calf blood flow decreased (-26%). No changes occurred in the mannitol or saline groups. Changes in plasma osmolality, plasma volume, splanchnic oxygen extraction and vasoactive hormones, including vasoactive intestinal polypeptide and glucagon, did not appear to be involved in the mechanism of these vasoactive phenomena. It is suggested that the possible deleterious effects of increase in portal pressure and azygos blood flow should be taken into consideration when administering hypertonic glucose to patients with portal hypertension.

Blood Glucose↗
PubMedDate not supplied

Postprandial hemodynamic responses in patients with cirrhosis.

The hemodynamic response to a 800 kcal liquid meal was investigated in 24 patients (study group) with cirrhosis and two control groups. One control group of six cirrhotic patients (volume control) had a calorie-free equivolumic electrolyte solution. The second control group (normal control) of six patients with normal hepatic function had the same test meal. Cardiac index, mean arterial pressure, heart rate, hepatic venous pressures, hepatic blood flow and azygos blood flow (only measured in the study group) were measured before and 30 and 60 min after the meal. Systemic circulatory responses were generally absent. Hepatic blood flow and wedged hepatic venous pressure increased significantly in both cirrhotic patients and normal controls; however, cirrhotic patients tended to have a quicker response (peaks at 30 min) than normals (peaks at 60 min). Azygos blood flow showed large postprandial variability, but overall did not change significantly. These results demonstrate that the splanchnic circulation of the patient with cirrhosis reacts differently from normals to the physiologic stimulus of a meal, and in particular appears to have precocious vasoactive reactivity.

Alcoholism↗
PubMedDate not supplied

Glucagon selectively increases splanchnic blood flow in patients with well-compensated cirrhosis.

To delineate the circulatory effects of glucagon in cirrhosis, we infused two moderately supraphysiological doses of this hormone into 19 patients with cirrhosis and determined hemodynamic responses. Patients were divided into a group with good liver function (Pugh Class A, n = 8) and poorer function (Pugh Class B and C, n = 11). All patients received glucagon at 10 ng per kg per min for 20 min, then 20 ng per kg per min for a further 20 min. These doses raised serum glucagon levels to a similar degree in both groups of patients. Serum glucose levels also rose in both groups but to a lesser degree in Class BC patients. Serum noradrenaline and adrenaline remained unchanged in both groups. Heart rate, mean arterial pressure, cardiac index, systemic vascular resistance, hepatic venous pressure gradient and hepatic blood flow were measured basally and during the second glucagon infusion. None of these measurements significantly changed in either group of patients. Azygos and renal venous blood flow were measured basally and during the first and second infusions. Azygos flow increased significantly only in Group A patients: basal, 0.32 +/- 0.03 liter per min; first infusion, 0.40 +/- 0.06 liter per min; second infusion, 0.49 +/- 0.07 liter per min. Corresponding values in Group BC patients were: 0.54 +/- 0.08, 0.54 +/- 0.08 and 0.52 +/- 0.08 liter per min. Renal blood flow did not change significantly. One patient with a portacaval shunt increased superior mesenteric venous flow from 0.78 liter per min to 0.95 liter per min with glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Long-term management of variceal bleeding: the place of pharmacotherapy.

Portal hypertension is treated by reducing portal pressure in order to prevent esophageal variceal bleeding or recurrent bleeding. Because portal hypertension depends on both elevated portal tributary blood flow and intrahepatic vascular resistance, the pharmacologic therapy of this syndrome consists in reducing portal blood flow or vascular resistance, or both. The pharmacologic prevention of first bleeding or recurrent bleeding has been performed with nonselective beta-adrenergic antagonists (propranolol or nadolol). Certain controlled studies have shown that this type of drug significantly reduces the risk of first bleeding by approximately 40% in patients with esophageal varices. A meta-analysis showed that death due to bleeding was also significantly lower in the beta-blocker group than in the placebo group. Moreover, beta-blockers are effective in patients in both good and poor condition and with all types of cirrhosis. The efficacy of beta-blockers on the risk of recurrent bleeding is less clear, but these substances significantly decrease the risk of rebleeding, by approximately 30%. Recurrent bleeding in patients treated with beta-blockers is associated with the occurrence of hepatocellular carcinoma or lack of compliance. In conclusion, it is clear that different substances have portal hypotensive effects and can be used to treat or prevent complications of portal hypertension. However, other drugs should be tested, and other clinical studies are needed to identify good responders.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Effects of alpha 1 and beta-adrenergic antagonists and 5-hydroxytryptamine receptor antagonist on portal-systemic collateral vascular resistance in conscious rats with portal hypertension.

In order to study the acute effects of pharmacological agents on the vascular resistance of portal-systemic collaterals, a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the conscious rat. The haemodynamic effects of several vaso-active substances were evaluated in this model and compared with those obtained after saline administration. Prazosin (0.5 mg), an alpha 1-adrenergic antagonist, significantly reduced mean arterial pressure by 29%, portal pressure from 13.8 +/- 1.0(mean +/- s.e.m.) to 10.1 +/- 0.4 mmHg and portal tributary blood flow (radioactive microspheres) from 13.6 +/- 2.1 to 11.7 +/- 1.2 mL/min. It also decreased portal-systemic vascular resistance from 95 +/- 16 to 73 +/- 9 dyn s/cm5 x 10(3). Propranolol (4 mg), a beta-adrenergic antagonist, significantly reduced mean arterial pressure by 12% and portal pressure from 15.5 +/- 1.2 to 13.3 +/- 0.9 mmHg while reducing portal tributary blood flow from 14.6 +/- 1.5 to 11.0 +/- 1.7 mL/min and increasing portal systemic collateral vascular resistance from 88 +/- 7 to 103 +/- 8 dyn s/cm5 x 10(3). Ketanserin (0.25 mg/kg), a 5-hydroxytryptamine receptor antagonist, reduced portal pressure from 15.8 +/- 1.0 to 13.3 +/- 0.7 mmHg at a dose that did not alter mean arterial pressure or portal tributary blood flow. It achieved this by reducing portal-systemic collateral vascular resistance from 90 +/- 14 to 74 +/- 13 dyn s/cm5 x 10(3). Saline had no significant effect on systemic and splanchnic haemodynamics. This study shows that ketanserin decreases vascular resistance of portal-systemic collaterals while propranolol increases it. Thus, it is suggested that collateral vascular resistance is accessible to pharmacological manipulation.

Animals↗
PubMedDate not supplied

[Relation between plasma catecholamines, the severity of the liver disease and hemodynamics in patients with cirrhosis].

Plasma noradrenaline and adrenaline concentrations were measured in 75 patients with cirrhosis in order to attempt to correlate these concentrations and liver failure and hemodynamic changes. The increased noradrenaline concentration was not correlated with the degree of liver failure estimated by Pugh's classification, with the cause of cirrhosis, with the presence of acute alcoholic hepatitis or with the presence of ascites. Adrenaline concentration was higher in cirrhotic patients with acute alcoholic hepatitis than in those without these lesions. Noradrenaline concentration was significantly correlated with heart rate, wedged hepatic venous pressure and renal blood flow. Noradrenaline concentration was also negatively correlated with stroke volume and adrenaline concentration was negatively correlated with cardiac output and stroke volume. These findings confirm the relationships between portal hypertension, sympathetic hyperactivity and renal function in patients with cirrhosis.

Adult↗
PubMedDate not supplied

[Effect of the development of portosystemic shunts in the maintenance of portal hypertension in rats].

We studied the role of portosystemic shunt development in the maintenance of portal hypertension in a prehepatic portal hypertension rat model. A first group was studied two days after partial portal vein ligation. When portosystemic shunts were negligible; the second group was studied 3 weeks after the partial portal vein ligation, when large portosystemic shunts were present. Portal pressure was significantly higher in the first group than in the second group (19.9 +/- 0.8 mmHg (mean +/- 1 SD) and 12.8 +/- 2.3 mmHg, respectively; p less than 0.001). When compared with sham operated rats: a) portal tributary blood flow (measured with the radioactive microspheres method) was decreased in the first group (- 34 p. 100; p less than 0.01) and increased in the second group (+ 32 p. 100; p less than 0.02); b) portal system vascular resistance was markedly increased in the first group (+ 269 p. 100; p less than 0.001) and did not significantly change in the second group (+ 30 p. 100). These results suggest that portosystemic shunt development decreases portal pressure but not to normal value because portal tributary blood flow is increased. Moreover the increase in portal system vascular resistance and in portal tributary blood flow play different roles in the maintenance of portal hypertension depending on the stage of evolution of portal hypertension.

Acute Disease↗