[Beta-adrenergic antagonists and endoscopic sclerotherapy for the prevention of digestive hemorrhage].
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Adrenergic beta-Antagonists↗
Biomedical subjects
D Lebrec
Publications and source records attributed to D Lebrec.
Relationships between plasma atrial natriuretic peptide concentrations and hemodynamics and hematocrit in patients with cirrhosis.
We studied the relationships in 29 patients with cirrhosis between pulmonary arterial atrial natriuretic peptide concentrations and the following: systemic and splanchnic hemodynamics, the hematocrit, arterial oxyhemoglobin saturation, oxygen tension and the severity of cirrhosis. Plasma atrial natriuretic peptide concentrations ranged from 21 to 208 pg/ml and averaged 78 +/- 8 pg/ml (mean +/- S.E.M.). Simple regression analysis showed significant correlations between plasma atrial natriuretic peptide concentration and the following: hematocrit, mean pulmonary arterial pressure, wedged hepatic venous pressure, free hepatic venous pressure, pulmonary wedged pressure and serum bilirubin concentrations. No significant correlations were found between plasma atrial natriuretic peptide concentrations and all other hemodynamic values, arterial oxyhemoglobin saturation and oxygen tension. Multiple stepwise regression analysis showed that the hematocrit, mean pulmonary arterial pressure and wedged hepatic venous pressure were significant and independent predictors of pulmonary artery plasma atrial natriuretic peptide concentrations (R2 = 0.69). Partial regression coefficients were -0.74 (p less than 0.001), 0.61 (p less than 0.001) and 0.44 (p less than 0.05) for the hematocrit, the mean pulmonary arterial pressure and the wedged hepatic venous pressure, respectively. In conclusion, in patients with cirrhosis, increased plasma atrial natriuretic peptide concentrations were related to the degree of hemodilution, increased pulmonary arterial pressure and the degree of portal hypertension. Plasma atrial natriuretic peptide concentrations were not influenced by the arterial oxygenation levels.
Arteries↗
Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats.
The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine in patients with cirrhosis.
The effects of dopamine on kidney function have not been elucidated in patients with cirrhosis. Moreover, although increased portal pressure has been observed with supradopaminergic doses of dopamine in these patients, the splanchnic hemodynamic effects of low doses of dopamine have not been previously studied. Thus we studied the acute systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine (1.5 micrograms/kg body wt min) in nine cirrhotic patients. Plasma dopamine levels increased markedly from 35 +/- 20 pg/ml to 31,400 +/- 4,900 pg/ml during dopamine administration. A significant diastolic pressure decrease of 10% was associated with a 15% increase in heart rate. Cardiac output was not altered. Although dopamine significantly increased azygos blood flow by 16%, wedged and free hepatic venous pressures were not altered. Dopamine significantly increased renal blood flow by 31%, but did not change the glomerular filtration rate. We conclude that a dopaminergic dose of dopamine increases azygos blood flow but not the hepatic venous pressure gradient. Finally, although it increases renal blood flow, dopamine does not seem to have any beneficial effects on glomerular filtration rate in cirrhotic patients.
Dopamine↗
Plasma catecholamines in patients with presinusoidal portal hypertension: comparison with cirrhotic patients and nonportal hypertensive subjects.
During a hemodynamic study, plasma catecholamine concentrations were measured in the pulmonary artery and in the hepatic vein in 18 presinusoidal portal hypertensive patients. Results were compared with those in 15 nonportal hypertensive subjects and in 24 cirrhotic patients in good condition (grade A, according to Pugh's classification). Plasma norepinephrine concentrations in the pulmonary artery or in the hepatic vein were not significantly different between nonportal hypertensive subjects (mean +/- S.E.M.: 271 +/- 36 and 83 +/- 11 pg/ml, respectively) and presinusoidal portal hypertensive patients (273 +/- 33 and 84 +/- 11 pg/ml, respectively). These concentrations were, however, elevated in cirrhotic patients (408 +/- 47 and 256 +/- 45 pg/ml, p less than 0.05 in comparison with the two other groups). These differences suggest that increased sympathetic nervous activity in cirrhosis is associated with the presence of liver disease or increase in sinusoidal pressure. Differences in plasma epinephrine concentrations were not significant among the three groups of patients. However, the existence of a significant correlation between pulmonary artery plasma epinephrine concentration and cardiac index (r2 = 0.46, p less than 0.01) in patients with presinusoidal portal hypertension suggests that the adrenal medulla could play a role in the pathophysiology of the hyperkinetic syndrome of these patients.
Adult↗
Beta-blockers for preventing variceal bleeding.
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Adrenergic beta-Antagonists↗
beta-blockers and variceal haemorrhage.
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Adrenergic beta-Antagonists↗
[Physiology of the portal system and physiopathology of portal hypertension].
Circulation in the territory of the portal vein is made up of blood flows in the organs of this territory. Each of these organs has an intrinsic and extrinsic regulatory system. Portal hypertension results from a simultaneous increase of intrahepatic portal vascular resistances and blood flow rates. The rise in vascular resistance is due to a decrease of the intrahepatic vascular space consecutive to fibrosis and lesions of the liver cells. The cause of the increase in blood flow is imperfectly known. Physical, metabolic, hormonal and nervous factors may be responsible for these splanchnic circulatory changes, and they also produce changes in systemic haemodynamics.
Animals↗
Desensitization of myocardial beta-adrenergic receptors in cirrhotic rats.
Cardiac responses to catecholamines are known to be attenuated in chronic liver disease. To elucidate the role of beta-adrenergic receptor alteration in this phenomenon, we measured heart rate responsiveness to isoprenaline and myocardial beta-adrenergic receptor-binding characteristics in three groups of rats: those that were sham operated, those that had portal vein stenosis and those that were cirrhotic because of bile duct ligation. Responsiveness to isoprenaline was evaluated in conscious rats by the dose of isoprenaline needed to increase basal heart rate by 50 beats/min and by the maximal heart rate response. beta-Receptor characteristics in heart membranes were derived from 125I-iodocyanopindolol binding data. Compared with sham-operated controls, cirrhotic rats needed a significantly higher dose of isoprenaline to raise basal heart rate by 50 beats/min (102.3 +/- 19.1 vs. 28.3 +/- 11.3 ng/kg) and lower maximal heart rate response (104 +/- 29 vs. 158 +/- 61 beats/min). In addition, myocardial beta-receptor density was significantly lower in cirrhotic rats (26.5 +/- 4.6 vs. 37.5 +/- 10.3 fmol/mg protein) and the dissociation constant was higher (31.6 +/- 17.0 vs. 14.0 +/- 2.5 pmol/L). Analysis of beta 1/beta 2 subpopulations revealed that the decreased total beta-receptor density was entirely due to selective beta 1-receptor down-regulation. beta-Receptor affinity for agonist was not altered in cirrhotic rats. Rats with portal vein stenosis showed no significant differences in either isoprenaline responsiveness or beta-receptor characteristics when compared with controls. These results indicate that beta-adrenergic receptor down-regulation may be responsible for the myocardial hyporesponsiveness to catecholamines observed in cirrhosis.
Animals↗
Portal hypertension: serotonin and pathogenesis.
It has been demonstrated that serotonin (5-hydroxytryptamine; 5HT) can decrease portal vascular resistance in animals and could be a possible mediator for intestinal vasodilatation. Moreover, isolated mesenteric vein from portal hypertensive rats has been shown to be hyper-responsive to 5HT. Hence 5HT may play a role in the pathophysiology of the hyperkinetic syndrome observed in patients with portal hypertension. This hypothesis that serotonin might increase splanchnic blood flow, and hence portal pressure, led us to propose that 5HT receptor antagonists might decrease portal hypertension. We observed that acute administration of ketanserin, an antagonist of serotonin at 5HT2 receptors, significantly decreased portal pressure and portal-systemic collateral blood flow in patients with cirrhosis, whereas hepatic blood flow was not modified. Arterial pressure slightly decreased, while cardiac output was not affected by ketanserin. These findings were also observed during continuous administration of ketanserin. More recently, it has been shown that ritanserin, a more specific 5HT2 receptor antagonist, significantly decreased portal pressure in cirrhotic patients. Finally, in rats with portal hypertension, ketanserin as well as ritanserin produced significant reductions in portal pressure but did not modify portal tributory blood flow. In these portal hypertensive animals, 5HT2 antagonists may act on hepatocollateral vascular resistance. These studies confirm current evidence in favor of a role for the actions of serotonin via 5HT2 receptors in portal hypertension and add a new group of substances for its treatment.
Animals↗
Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis.
The sensitivity of ultrasonography (US) for the diagnosis of portal hypertension was assessed in 48 patients with known cirrhosis. These results were compared to the hemodynamic values obtained on the same day by hepatic vein catheterization. The sensitivity of US in detecting portal hypertension was about 40% considering either a greater than 13 mm diameter of the portal vein, or the lack of mild caliber variation of the superior mesenteric vein. The sensitivity was more than 80% considering the presence of portosystemic venous collaterals. Presence of numerous portosystemic shunts was significantly associated with high hepatic venous pressure gradients which reflected the severity of portal hypertension.
Female↗
Hemodynamic effects of dopamine in conscious rats with secondary biliary cirrhosis.
Dopamine may be used in cirrhotic patients with renal or circulatory failure, but this drug can also increase the degree of portal hypertension. Hence, the systemic and splanchnic hemodynamic effects of dopamine have been studied in portal hypertensive rats with secondary biliary cirrhosis. The dose-response curves showed that dopamine significantly increased portal pressure at the same dose (80 micrograms min-1 kg-1 body wt.) in normal and biliary cirrhotic rats. Arterial pressure only increased with higher doses of dopamine in rats with biliary cirrhosis (160 micrograms min-1 kg-1 body wt.) while in normal animals it increased (80 micrograms min-1 kg-1 body wt.). Dopamine (160 micrograms min-1 kg-1 body wt.) significantly increased mean arterial pressure in normal and biliary cirrhotic rats. It significantly increased cardiac output in biliary cirrhotic rats from 134 +/- 6 to 153 +/- 7 ml/min but not in normals. Accordingly, systemic vascular resistance increased significantly in normal rats but not in cirrhotics. Portal pressure increased significantly in normal rats from 8.0 +/- 0.3 to 12.1 +/- 0.6 mmHg and in rats with biliary cirrhosis from 15.9 +/- 1.0 to 19.0 +/- 1.3 mmHg. Portal tributary blood flow increased significantly in normal and biliary cirrhotic rats (14.1 +/- 1 to 20.9 +/- 2.3 ml/min and 18.0 +/- 0.9 to 25.5 +/- 1.8 ml/min, respectively). This study shows that an elevated dose of dopamine increases the hyperkinetic syndrome in rats with secondary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nitrovasodilators and portal hypertension.
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Humans↗
Current status and future goals of the pharmacologic reduction of portal hypertension.
The continuous oral administration of different drugs can produce a sustained reduction in portal pressure in patients with portal hypertension. beta-Adrenergic antagonists, alpha 2-adrenergic agonists, and 5-hydroxytryptamine-receptor antagonists have been evaluated for their long-term effects on portal pressure reduction. Clinical studies show that gastrointestinal bleeding can be prevented by pharmacologic therapy. This type of treatment is efficient and safe, and, if a drug has no clinical effect, a different drug or a combination can be used. Several problems, however, need to be addressed, including patient compliance, selection of responders, and hemodynamic evaluation of the treatment and its duration. Although pharmacologic treatment of portal hypertension is known to be efficient, there are advances still to be made.
Adrenergic alpha-Agonists↗
Effects of haemorrhage and volume expansion on portal-systemic collateral vascular resistance in conscious portal hypertensive rats.
1. In order to study the acute effects of blood volume changes on the vascular resistance of portal-systemic collaterals (collateral vascular resistance), a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the rat. In this model, we determined the haemodynamic effects of haemorrhage (1.8 ml/100 g body weight) or intravenous infusion of a volume expander (1.8 ml/100 g body weight). Cardiac output and regional blood flows were measured by the radioactive microsphere method. 2. Haemorrhage significantly reduced arterial pressure from 108 +/- 4 to 92 +/- 4 mmHg (mean +/- SEM), cardiac output from 56 +/- 4 to 24 +/- 2 ml min-1 100 g-1 body weight, portal pressure from 15.1 +/- 1.5 to 10.0 +/- 1.4 mmHg and portal tributary blood flow from 19.9 +/- 2.3 to 8.3 +/- 1.4 ml/min. Consequently, collateral vascular resistance significantly increased from 6.6 +/- 0.9 x 10(3) to 11.1 +/- 2.0 x 10(3) kPa 1(-1) s. 3. Volume expansion reduced arterial pressure from 98 +/- 3 to 90 +/- 3 mmHg, and significantly increased cardiac output from 43 +/- 3 to 55 +/- 3 ml min-1 100 g-1 body weight, portal pressure from 13.9 +/- 0.7 to 16.5 +/- 0.8 mmHg and portal tributary blood flow from 16.4 +/- 1.3 to 28.2 +/- 3.2 ml/min. Consequently, collateral vascular resistance significantly decreased from 7.0 +/- 0.5 x 10(3) to 4.9 +/- 0.4 x 10(3) kPa l-1 s. 4. This study shows that in rats with portal hypertension, portal-systemic collateral vascular resistance is modified by alterations in blood volume.
Animals↗
Effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in normovolemic and hypovolemic cirrhotic rats.
The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg.kg-1.min-1 iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P less than 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P less than 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P less than 0.05) and was similar to those receiving isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Heterogeneous hepatic venous pressures in patients with liver cancer.
We carried out hepatic vein catheterization in 73 patients with liver cancer, 52 with primary and 21 with metastatic cancer. A heterogeneous hepatic venous pressure gradient, defined as a difference of greater than 4 mmHg between the highest and lowest values of the pressure gradient in any patient, was found in 46% of the hepatocellular carcinoma cases and 43% of the metastatic cancers. Comparing the diagnostic efficacy of this phenomenon with an elevated alpha-fetoprotein, based on 500 randomly selected catheterizations, showed that the heterogeneous gradient was 46% sensitive and 99% specific for the diagnosis of hepatocellular carcinoma, while the alpha-fetoprotein was 67% sensitive and 99% specific. Positive and negative predictive values were 86 and 95%, respectively, for the heterogeneous gradient, and 83 and 97% for the alpha-fetoprotein. Its expense and relative invasiveness make hepatic vein catheterization an unacceptable routine in patients suspected of having hepatic malignancy. However, we suggest that the unexpected finding of a heterogeneous pressure gradient should trigger a search for hepatic cancer.
Adult↗
Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in a Caribbean patient.
Membranous obstruction of the inferior vena cava has been reported mainly in South Africa, Japan, and India; in 20-40% of patients the disease is complicated by hepatocellular carcinoma. We report a case of membranous obstruction of the inferior vena cava with hepatocellular carcinoma in a 43-year-old Caribbean man of Indian origin. The Caribbean islands may constitute another geographical area where the population is at risk for the development of membranous obstruction of the inferior vena cava and subsequent hepatocellular carcinoma.
Adult↗