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Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

At least 235 records · Page 13Linked to original sources
PubMed1988

Model for the study of portal-systemic collateral vascular resistance in the conscious rat.

In order to obtain a model for the study of portal-systemic collateral vascular resistance, total portal vein occlusion was performed in rats 48 hr or 3 wk after partial obstruction. Four groups of conscious restrained rats were studied: a) sham-operated, b) partial portal vein ligated, c) 48 hr-total portal vein occluded, and d) 3 wk-total portal vein occluded. In comparison with the sham group, the three portal vein ligated groups had significantly higher cardiac output, portal tributary blood flow, portal pressure (7.7 +/- 0.4 versus 13.5 +/- 0.5, 13.6 +/- 0.8, and 17.7 +/- 1.1 mmHg, mean +/- SE, respectively) and hepatic arterial blood flow (5.8 +/- 0.6 versus 9.5 +/- 0.7, 8.3 +/- 0.5, and 13.9 +/- 1.9 ml/min, respectively). Cardiac output and portal tributary blood flow did not differ between the portal vein ligated groups, but portal pressure and hepatic arterial blood flow were significantly higher in the 3 wk-total portal vein occlusion group. The 3 wk-total portal vein occlusion group showed 99.1 +/- 0.3% shunting, different from the partial (29.7 +/- 16.9%, p less than 0.01) and 48 hr-total portal vein occlusion (46.5 +/- 14.7%, p less than 0.05) groups. Portography confirmed absence of portal-portal collaterals in the 3 wk-total portal vein occlusion group. It is suggested that rats with 3 wk-total portal vein occlusion are useful for the study of acute modifications of portal-systemic collateral circulation, as shunting is total and consistent in this model.

Animals↗
PubMed1988

Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial.

This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointestinal bleeding in cirrhotic patients with large oesophageal varices who had never bled. Nadolol or placebo was given randomly to two groups of 53 patients. The percentage of patients free of gastrointestinal bleeding 1 year after inclusion in the study was 83 +/- 6% (mean +/- S.D.) in the nadolol group and 80 +/- 6% in the placebo group. In the nadolol and placebo groups, 40 and 47 patients, respectively, were compliant, i.e., took nadolol or placebo continuously. The percentage of patients who were free of bleeding 1 year after inclusion was 97 +/- 3% in the subgroup of compliant nadolol patients. This percentage was significantly higher than that of patients who were free of bleeding in the placebo group (P less than 0.03) as well as in the subgroup of compliant placebo patients (77 +/- 6%; P less than 0.02). We concluded that, although there was no overall significant effect of nadolol on the risk of bleeding in cirrhotic patients in good condition with large oesophageal varices, this study suggests that nadolol reduced the risk of bleeding in compliant patients.

Clinical Trials as Topic↗
PubMed1988

Effects of nitroglycerin on forearm haemodynamics in patients with cirrhosis.

1. Basal forearm haemodynamics were studied by venous occlusion plethysmography in three groups of subjects: group I, healthy controls, group II, patients with cirrhosis age- and sex-matched with group I, and group III, an older group of patients with cirrhosis. Subsequently, responses to sublingual nitroglycerin were measured in group I and II subjects. 2. Controls responded to nitroglycerin with an increase in venous distensibility; group II patients had higher initial venous distensibility but did not respond to nitroglycerin. No other variables in either group were affected by nitroglycerin. 3. Group II and III patients differed in forearm blood flow and vascular resistance and venous distensibility. A significant inverse correlation was found between age and forearm blood flow (r = 0.57, P less than 0.001) in all patients with cirrhosis. 4. We conclude that (a) venous tone is reduced in cirrhosis, possibly as a result of chronic venodilatation; (b) this venodilatation impedes further dilatory response to a small dose of nitroglycerin; (c) cirrhosis is also associated with age-related decreases in peripheral haemodynamics.

Adolescent↗
PubMed1988

Comparative haemodynamic effects of betaxolol and propranolol in patients with cirrhosis.

The acute effects of betaxolol (10 mg, intravenously), a new cardioselective beta-blocker, and propranolol (15 mg, intravenously) on splanchnic and systemic circulations were studied in two matched groups of six patients with portal hypertension due to cirrhosis. Similar decreases in hepatic venous pressure gradient and azygous blood flow--an estimation of superior portosystemic shunts--were observed after both drugs, whereas hepatic blood flow was not modified. The decreases in heart rate and cardiac index were also similar after betaxolol and propranolol. Both drugs induced a significant decrease in the fraction of cardiac output flowing through superior portosystemic shunts. These findings confirm that the marked effect of beta-adrenoceptor blocking agents on splanchnic circulation results both from the reduction in cardiac output and from a vasoconstriction of the portal vein territory, and demonstrate that this vasoconstriction of the portal vein area does not necessitate a beta 2-blocking activity of the drug. The similar efficiency of the two agents in decreasing the hyperkinetic circulation suggests that betaxolol merits further long-term study in the pharmacologic treatment of portal hypertension.

Adrenergic beta-Antagonists↗
PubMed1988

Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter.

To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Cardiac output and regional blood flows were measured twice, 10 min apart, in pentobarbital anesthetized or awake, sham-operated or portal vein-ligated rats, with or without portal cannulation. Variability between the two successive measurements was not affected by portal hypertension or portal cannulation, and was not different in the splanchnic territory and in other organs. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output (53.9 +/- 3.0 vs 45.8 +/- 2.9 ml.min-1.100 g body wt-1, P less than 0.01) and splanchnic blood flow (12.31 +/- 0.72 vs 9.34 +/- 0.85 ml.min-1.100 g body wt-1, P less than 0.01) were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure (100.2 +/- 4.3 vs 119.9 +/- 3.4 mm Hg, P less than 0.01) and heart rate (366.5 +/- 10.0 vs 405.5 +/- 7.4 beats.min-1, P less than 0.01) were elevated. Anesthesia also decreased portal pressure (14.8 +/- 0.5 vs 12.0 +/- 0.4 mm Hg, P less than 0.05) in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state.

Animals↗
PubMed1987

Plasma from cirrhotic patients induces inotropic changes on cultured rat heart cells.

Cultured monolayers of newborn rat heart cells were perfused with plasma from patients with alcoholic liver cirrhosis. The results showed that cirrhotic plasma, when compared to control plasma, depressed contractility of beating cardiac cells. The in-vitro deleterious effects of plasma from cirrhotic subjects on cell cultures were neither related to hemodynamic parameters nor to the levels of plasmatic catecholamines. This study suggests the presence in the plasma of patients with alcoholic liver cirrhosis, of humoral factor(s) which cause depressive effects on rat heart cells in culture.

Animals↗
PubMed1987

Relationship between degree of portal hypertension and liver histologic lesions in patients with alcoholic cirrhosis. Effect of acute alcoholic hepatitis on portal hypertension.

The relationship between the degree of portal hypertension and histologic liver lesions was studied in a group of 84 patients with histologically proven alcoholic cirrhosis. The degree of portal hypertension was evaluated by the gradient between wedged and free hepatic venous pressures. Five histologic lesions were quantified: liver cell necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis, and fatty infiltration. The gradient between wedged and free hepatic venous pressures was significantly correlated with the degree of liver cell necrosis and the degree of neutrophilic infiltrate. The stepwise regression analysis showed that only liver cell necrosis has a significant and independent correlation for the degree of portal hypertension. The value for the gradient between wedged and free hepatic venous pressures was significantly higher in patients with (N = 48) than in those without (N = 36) acute alcoholic hepatitis (19.4 +/- 0.8 and 16.5 +/- 0.7 mmHg, respectively). Thus, histologic liver lesions observed in acute alcoholic hepatitis may play a role in the risk of complications of portal hypertension in patients with alcoholic cirrhosis.

Acute Disease↗
PubMed1987

Reduction of intrahepatic vascular space in the pathogenesis of portal hypertension. In vitro and in vivo studies in the rat.

To elucidate a possible role for reduction of intrahepatic vascular space in the pathogenesis of portal hypertension, we studied a partially hepatectomized rat model in vitro and in vivo. The in vitro study used livers from normal, 1/3-hepatectomized, and 2/3-hepatectomized rats, and rats with cirrhosis caused by chronic bile duct ligation, for isolated, perfused flow-pressure plotting. Resistance to perfusion increased such that significant differences were found between all groups except the last two, which showed similar resistances. The in vivo study measured splanchnic blood flow by radioactive microspheres and portal pressure in anesthetized sham-operated and 1/3- and 2/3-hepatectomized rats. Although absolute portal tributary blood flows did not change, portal flow per gram of remnant liver showed significant increases: 1.57 +/- 0.32 ml/min X g liver, 2.52 +/- 0.60 ml/min X g liver, p less than 0.01; 3.48 +/- 1.04 ml/min X g liver, p less than 0.01, respectively. Although intrahepatic resistance increased significantly only in the 2/3-hepatectomized group, portal pressures increased significantly in both groups of hepatectomized rats: normal, 7.5 +/- 1.1 mmHg; 1/3-hepatectomized, 9.4 +/- 1.1 mmHg; and 2/3-hepatectomized, 11.1 +/- 1.2 mmHg. Thus, decreased intrahepatic vascular space caused by resection and hepatocellular hypertrophy leads to portal hypertension, thereby suggesting that this reduction in space may be the pathogenic factor common to a number of different theories of portal hypertension.

Animals↗
PubMed1987

Reversal of adrenaline-induced increase in azygos blood flow in patients with cirrhosis receiving propranolol.

In patients with cirrhosis, endogenous catecholamines may influence the circulatory effects of propranolol. We intended to evaluate the interaction of adrenaline and propranolol on azygos blood flow, an estimate of blood flow in the superior portosystemic collateral circulation. We investigated 6 patients with cirrhosis, 5 with good liver function, receiving an intravenous infusion of adrenaline (50 ng/kg/min) before and after administration of propranolol. The median value for baseline azygos blood flow was increased from 700 ml/min (range 340-1 470 ml/min) to 1 050 (range 570-1 840 ml/min) with adrenaline alone (P less than 0.05), and decreased to 610 ml/min (range 260-1 190 ml/min) with propranolol alone (P less than 0.05). The infusion of adrenaline given after propranolol further reduced azygos blood flow to a median value of 530 ml/min (range 200-730 ml/min) (P less than 0.05). Thus, following beta-adrenergic blockade, there is a reversal of the effects of adrenaline on azygos blood flow, which corresponds to a potentiation of the effects of propranolol. Similar endogenous adrenaline-propranolol interactions may play a role in preventing recurrent variceal bleeding in cirrhotic patients.

Adult↗
PubMed1987

Oxygen and bile acid content in the azygos blood. Clues to the azygos derivation in patients with portal hypertension.

In patients with cirrhosis, elevation of azygos blood flow has been attributed on indirect grounds to cephalad portosystemic collaterals. To gather more information on the origin of the azygos blood, we studied the oxygen and bile acid content of the azygos and mixed venous blood in patients with portal hypertension. Azygos oxygen saturation was 59.6 +/- 6.0% in 8 controls, and significantly higher in 35 patients with cirrhosis (76.7 +/- 7.6%; P less than 0.01) as well as in 6 patients with noncirrhotic portal hypertension (84.0 +/- 8.2%; P less than 0.01). High oxygen saturation, however, was not correlated to azygos blood flow in patients with cirrhosis. In cirrhotic patients, total bile acid concentrations were 28.1 +/- 20.4 mumol/l in the pulmonary artery and 25.9 +/- 17.6 mumol/l in the azygos vein, giving an azygos to mixed venous ratio of 0.95 +/- 0.18. These results provide new evidence that elevated azygos blood flow in patients with portal hypertension is derived from the portal system, and perhaps predominantly from the splenic territory.

Azygos Vein↗
PubMed1987

Failure of haemodynamic measurements to predict recurrent gastrointestinal bleeding in cirrhotic patients receiving propranolol.

In an attempt to identify the haemodynamic factors predicting the recurrence of gastrointestinal bleeding in cirrhotic patients receiving propranolol, haemodynamic measurements were prospectively collected. Systemic and splanchnic haemodynamics were assessed before propranolol administration. Among 77 patients receiving propranolol, 24 re-bled and 53 did not re-bleed in a follow-up period of 30-730 days (median 540). There was no difference between patients with and without recurrent bleeding with regard to the initial value of heart rate, mean arterial pressure, cardiac index, and hepatic venous pressure gradient. A subgroup of 43 patients was further investigated for the haemodynamic response to one single dose of 40 mg of propranolol. No difference was observed in the propranolol-induced changes of heart rate, mean arterial pressure, cardiac index or hepatic venous pressure gradient, between patients with (n = 14) and those without (n = 29) recurrent bleeding while taking propranolol. In conclusion, systemic haemodynamics and hepatic venous pressure gradient have no predictive value in evaluating the risk of recurrent bleeding in cirrhotic patients receiving propranolol. Furthermore, therapeutic efficacy of propranolol cannot be predicted from the haemodynamic response to a single first dose of this substance.

Adult↗
PubMed1987

Naloxone does not alter haemodynamics in cirrhosis. Studies in humans and rats.

In order to test the hypothesis that endogenous opioids may mediate some of the circulatory derangements in cirrhosis, we studied the haemodynamic effects of naloxone, an opioid antagonist, in patients and in a rat model of biliary cirrhosis. In 9 patients with alcoholic cirrhosis and 5 control patients without significant liver disease, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate, hepatic venous pressures and O2 content, hepatic and azygos blood flows and serum catecholamines were measured before and 30 min after naloxone 3.2 mg i.v. bolus. No significant changes were observed in either group of patients. Similarly in 16 conscious rats, 8 sham-operated and 8 with cirrhosis due to bile duct ligation, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate, and splanchnic organ blood flows were measured by radioactive microspheres, before and 20 min after naloxone 1 mg/kg i.v. bolus. No significant changes were observed in either group. We failed to detect any evidence that endorphins are involved in tonic haemodynamic control in cirrhosis.

Adult↗
PubMed1987

Possible deleterious hemodynamic effect of nifedipine on portal hypertension in patients with cirrhosis.

The acute effects of nifedipine, 10 mg administered sublingually, were studied in 10 patients with alcoholic cirrhosis. Nifedipine significantly increased cardiac output and reduced systemic vascular resistance. Nifedipine also increased the hepatic venous pressure gradient by 15% (P less than 0.01). Hepatic blood flow and azygos blood flow did not change significantly. It is suggested that nifedipine increases portal pressure and thus may be deleterious to patients with portal hypertension.

Blood Pressure↗
PubMed1987

Hepatic sarcoidosis with portal hypertension. A report of seven cases with a review of the literature.

We have reviewed the clinical, histological and hemodynamic features of sarcoidosis complicated by portal hypertension in seven patients and in 40 previously reported cases. Young black patients of either sex and white females over 40 years were selectively affected. In 12 of these 47 patients, portal hypertension appeared to be a consequence of cirrhosis due to longstanding intrahepatic cholestasis; in white patients, this condition was clinically, histologically, and serologically indistinguishable from primary biliary cirrhosis. In most of the other patients, portal hypertension was the predominant and often the presenting symptom of hepatic sarcoidosis; in these patients portal hypertension was due to a presinusoidal block probably determined by portal granulomas, with or without superimposed sinusoidal block determined by fibrosis. Corticosteroids did not prevent the development of portal hypertension.

Adult↗