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Biomedical subjects

R Moreau

Publications and source records attributed to R Moreau.

At least 109 records · Page 6Linked to original sources
PubMed1995

Effects of superior mesenteric artery stenosis on splanchnic and systemic hemodynamics in conscious rats with biliary cirrhosis.

BACKGROUND/AIMS: Since portal tributary blood flow is increased in portal hypertension due to cirrhosis, a reduction in mesenteric arterial blood flow should decrease portal pressure. METHODS: Calibrated stenosis of the superior mesenteric artery was performed in bile duct ligated rats, using a 22-gauge needle. Arterial stenosis was performed 4 weeks after bile duct ligation. Hemodynamic studies were performed in the 5th week following bile duct ligation in conscious rats. RESULTS: At that time, no digestive tract alterations were observed. In rats with mesenteric arterial stenosis, portal pressure was 12.2 +/- 2.0 mmHg; this value was lower than in rats with cirrhosis without arterial stenosis (14.5 +/- 1.1 mmHg) but higher than normal rats (5.8 +/- 0.7 mmHg). In rats with cirrhosis with mesenteric arterial stenosis, portal tributary and mesenteric blood flows were lower than in rats with cirrhosis without arterial stenosis and not significantly different from normal rats. In rats with mesenteric stenosis, cardiac index was significantly lower than in rats with cirrhosis and not significantly different from normal rats. CONCLUSION: This study shows that calibrated superior mesenteric arterial stenosis normalized portal tributary blood flow and reduced but did not normalize the degree of portal hypertension.

Animals↗
PubMed1995

Plasma endotoxin and tumor necrosis factor-alpha in the hyperkinetic state of cirrhosis.

BACKGROUND/AIMS: The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-alpha may be elevated in patients with cirrhosis, and therefore the potential role of these substance was assessed in the hyperkinetic circulation in cirrhosis. METHODS: Forty-nine patients in stable condition underwent systemic and hepatic hemodynamic measurements, and right atrial blood sampling for endotoxin and tumor necrosis factor-alpha assays. Patients were divided into three groups according to the severity of the disease: group 1 consisted of eight patients with normal liver or mild hepatic fibrosis, and groups 2 and 3 contained 17 and 24 patients with Child A and Child B or C cirrhosis, respectively. RESULTS: Systemic vascular resistance decreased and cardiac index increased from group 1 to 3: 1530 +/- 196 dyn.s.cm-5 to 990 +/- 72 dyn.s.cm-5 (mean +/- S.E.; p<0.05) and 3.1 +/- 0.3 l.min-1.m-2 to 4.2 +/- 0.2 l.min-2.m-2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-alpha was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-alpha levels were not different among the groups (10 +/- 5, 18 +/- 5 and 17 +/- 7 pg/ml in groups 1, 2 and 3, respectively). Systemic vascular resistance and cardiac index were not correlated to plasma tumor necrosis factor-alpha levels; patients with increased levels of this cytokine did not have worse hyperdynamic circulation in any of the groups. CONCLUSIONS: These results suggest that tumor necrosis factor-alpha and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis.

Hemodynamics↗
PubMed1995

Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with severe cirrhosis.

BACKGROUND/AIMS: Endogenous pulmonary nitric oxide production may be increased in severe cirrhosis and contribute to pulmonary vasodilation. This study assessed pulmonary nitric oxide production by measuring nitric oxide in the exhaled air in patients with severe cirrhosis and examined the relationship between exhaled nitric oxide and pulmonary hemodynamics in these patients. METHODS: Nitric oxide concentrations and production were measured in the exhaled air in six Child-Pugh class C patients with cirrhosis and 21 non-smoking healthy controls. Systemic and pulmonary hemodynamics were measured in patients only. RESULTS: Nitric oxide concentration (32.0 +/- 1.7 (mean +/- SEM) vs. 8.9 +/- 1.0 ppb) and production (9.2 +/- 1.3 vs. 3.1 +/- 0.3 nmol/min) in exhaled air were significantly higher in patients than in controls. Patients had high cardiac output (8.5 +/- 0.9 l/min), low pulmonary and systemic vascular resistance (57 +/- 10 and 767 +/- 93 dyn.s.cm-5, respectively) under baseline conditions. A significant negative correlation was found between pulmonary vascular resistance and exhaled nitric oxide production (r=0.943, p=0.05) but not between cardiac output or systemic vascular resistance and nitric oxide measured in exhaled air. CONCLUSIONS: Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with cirrhosis and liver failure. Increased in patients with cirrhosis and liver failure. Increased nitric oxide production may also contribute to cirrhosis-induced pulmonary vasodilatation.

Female↗
PubMed1995

Blunted natriuresis and abnormal systemic hemodynamic responses to C-type and brain natriuretic peptides in rats with cirrhosis.

BACKGROUND/AIMS: The effects of C-type and brain natriuretic peptides (CNP and BNP, respectively) on renal excretion of sodium and hemodynamics have not yet been studied in cirrhosis. METHODS: This study aimed to examine the effects of saline, CNP (300 ng.kg-1.min-1 i.v. for 30 min) and BNP (600 ng.kg-1.min-1 i.v. for 30 min) on natriuresis and diuresis in normal and rats with cirrhosis. Moreover, regional and systemic hemodynamics were measured prior to and following CNP and BNP administration in normal rats and rats with cirrhosis with ascites. RESULTS: In rats with cirrhosis, the effects of CNP or BNP or natriuresis and diuresis did not significantly differ from the effects of saline. CNP significantly decreased portal pressure and systemic vascular resistance and significantly increased the cardiac index. BNP significantly decreased portal tributary blood flow, portal pressure and cardiac index. In normal rats, natriuresis and diuresis were significantly higher with CNP and BNP than with saline. Systemic hemodynamics were not changed by CNP. A decrease in arterial pressure was the sole BNP-induced hemodynamic change. CONCLUSIONS: In conclusion, this study shows that the natriuretic response to pharmacological doses of CNP and BNP is blunted in rats with cirrhosis. This blunting may be related to an activation of the endogenous antinatriuretic systems secondary to systemic vasodilation (by CNP) or to a decreased cardiac index (by BNP). Finally, this study shows that CNP and BNP have a portal hypotensive action.

Animals↗
PubMed1995

Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis.

BACKGROUND/AIMS: In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, alpha 1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown. METHODS: Thus, pressor dose-response curves to vasoconstrictors [phenylephrine (an alpha 1-agonist, 0.1-500 micrograms/kg) angiotensin II (10-500 ng/kg), vasopressin (0.01-5 IU/kg), and Bay K 8644 (an L-type calcium channel activator, 0.5-50 micrograms/kg)] were obtained in normal rats and in rats with secondary biliary cirrhosis. All experiments were performed in ganglionic-blocked animals to limit the influence of cardiovascular reflexes. Doses of vasoconstrictor necessary to obtain a 40 mmHg increase in arterial pressure (D40) were calculated. RESULTS: Compared to normal animals, rats with cirrhosis had significantly higher D40 values for angiotensin II (171 +/- 57 vs. 344 +/- 41 ng/kg), phenylephrine (2.6 +/- 0.2 vs. 26.4 +/- 10.7 micrograms/kg) and vasopressin (73 +/- 19 vs. 401 +/- 150 mU/kg). Pressor responses to Bay K 8644 did not differ between normal rats and rats with cirrhosis (8.8 +/- 0.9 vs. 10.5 +/- 2.1 micrograms/kg). CONCLUSIONS: In conclusion, this study shows that cirrhosis produces vascular hyporeactivity to phenylephrine, vasopressin and angiotensin II but not to Bay K 8644. Therefore, cirrhosis impairs certain constrictor mechanisms which are shared by phenylephrine, angiotensin II and vasopressin but which do not contribute to the vascular response to Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Short-term cardiovascular effects of somatostatin in patients with cirrhosis.

Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 micrograms) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 micrograms of somatostatin, followed by a 250 micrograms/h infusion for 65 min. A second bolus of 250 micrograms of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to 73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hemodynamics after orthotopic liver transplantation: study of associated factors and long-term effects.

Among 68 liver transplant recipients, 190 hemodynamic studies were performed to evaluate the role of sepsis, anemia, acute graft rejection, and persistent portosystemic shunts. The hemodynamic outcome after orthotopic liver transplantation (OLT) in stable patients was also determined. Patients with sepsis showed a significant increase in cardiac index (5.1 +/- 0.9 vs. 3.4 +/- 0.7 L/min m2) and hepatic venous pressure gradient (6.3 +/- 2.9 vs. 3.3 +/- 2.1 mm Hg), compared with patients without sepsis. Cardiac index was higher in patients with, than in patients without, anemia (4.1 +/- 0.6 vs. 3.0 +/- 0.6 L/min m2). The hepatic venous pressure gradient was higher in patients with than in patients without acute graft rejection (5.1 +/- 2.9 vs. 2.6 +/- 1.2 mm Hg). Among patients with acute rejection, the hepatic venous pressure gradient was higher in patients with severe rejection than in those with moderate or mild rejection (7.2 +/- 3.3 vs. 4.6 +/- 2.4 and 2.8 +/- 0.9 mm Hg). In the postoperative period, in patients undergoing transplantation for acute liver failure, the hepatic blood flow was normal and significantly lower than in patients receiving transplant for cirrhosis (1.15 +/- 0.37 vs. 1.96 +/- 0.71 L/min). In patients undergoing transplantation for cirrhosis, cardiac index, azygos, and hepatic blood flows significantly decreased after 1 year compared with the first 6 postoperative months. Multivariate analysis showed that sepsis, anemia, and time after OLT were independent variables influencing cardiac index. Sepsis, time after OLT, and the existence of portosystemic shunts were independent variables influencing hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis.

Serotoninergic mechanisms are thought to play a role in portal hypertension. Because this biomine is metabolized by the liver, peripheral blood and plasma levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid (the main metabolite of 5-hydroxytryptamine) were measured in 30 patients with cirrhosis. Whole-blood 5-hydroxytryptamine levels were significantly lower in patients with cirrhosis (158 +/- 28 nM) than in age-matched controls (332 +/- 19 nM), and no correlation was found between these levels and the severity of cirrhosis. Unconjugated plasma 5-hydroxytryptamine levels, an indication of the active form of 5-hydroxytryptamine, were significantly higher in patients with cirrhosis than in controls (6.8 +/- 1.7 nM and 3.4 +/- 0.5 nM, respectively), and in patients with cirrhosis these levels were higher in Pugh grade A than in Pugh grade C patients. Conjugated-plasma 5-hydroxytryptamine levels were not significantly different between patients with cirrhosis (32.2 +/- 8.1 nmol/L) and controls (16.4 +/- 1.4 nmol/L). Plasma 5-hydroxyindole acetic acid was significantly lower in patients with cirrhosis than in controls (1.5 +/- 0.1 nmol/L and 2.3 +/- 0.1 nmol/L, respectively). In conclusion, this study shows that serotoninergic mechanisms are altered in patients with cirrhosis.

Hepatic Veins↗
PubMed1994

Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis.

BACKGROUND/AIMS: Because the vasodilator nitric oxide is overproduced in cirrhosis, this substance may decrease pressor responses to the vasoconstrictor endothelin 1. This study aimed to examine the effects of a NO synthesis inhibitor (NG-nitro-L-arginine methyl ester; L-NAME) on vascular responsiveness to endothelin 1 in normal and cirrhotic rats. METHODS: Pressor dose-response curves to endothelin 1 (0.5, 1, 3, 6, and 10 micrograms/kg intravenously) were obtained in animals with or without pretreatment with L-NAME. RESULTS: Pressor responses to endothelin 1 alone were significantly lower in cirrhotic than in normal rats. In cirrhotic animals, pressor responses to 3, 6, and 10 micrograms/kg of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. The responses to the other doses of endothelin 1 were not affected by L-NAME. In normal rats, pressor responses to all doses of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. In animals pretreated with L-NAME, pressor responses to 6 and 10 micrograms/kg of endothelin 1 did not differ between cirrhotic and normal rats, whereas responses to other doses remained lower in cirrhotic than in normal rats. CONCLUSIONS: In rats with cirrhosis, NO seems to contribute to vascular hyporeactivity to high doses but not to low doses of endothelin 1.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Altered control of vascular tone by adenosine triphosphate-sensitive potassium channels in rats with cirrhosis.

BACKGROUND/AIMS: Because the activation of arterial adenosine triphosphate (ATP)-sensitive potassium (KATP) channels is known to induce vasodilation, these channels may contribute to baseline vasodilator tone in cirrhosis. This study aimed to examine hemodynamic responses to glibenclamide, a KATP channel blocker, and to aprikalim, a vasodilator activating KATP channels, in normal and cirrhotic rats. METHODS: Splanchnic and systemic hemodynamic responses to glibenclamide (2.5, 5, 20, 30 mg/kg, intravenously) were studied. The arterial pressure response to aprikalim (200 mu/kg, intravenously) was studied with and without glibenclamide pretreatment (20 mg/kg). RESULTS: In cirrhotic rats, glibenclamide (5, 20, 30 mg/kg but not 2.5 mg/kg) significantly increased vascular resistance in portal and systemic territories. In normal rats, the latter effects occurred with 20 and 30 mg/kg of glibenclamide only. Aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal rats. Following glibenclamide, aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal animals. CONCLUSIONS: In rats with cirrhosis, the glibenclamide-induced vasoconstriction indicates that a vasodilator tone due to KATP channel opening existed under baseline conditions. Moreover, this study suggests that the control of vascular tone by KATP channels is altered in cirrhosis.

Adenosine Triphosphate↗
PubMed1994

Effect of clonidine on liver oxygen extraction during alcohol withdrawal in man.

Since catecholamines can alter splanchnic oxygen transport and extraction, the suppression of sympathetic overactivity during alcohol withdrawal might improve hepatic oxygen extraction. Therefore, this study investigated the effects of clonidine, a centrally-acting alpha 2-agonist which reduces sympathetic nervous outflow, on splanchnic oxygen transport and extraction in 13 patients with chronic alcoholism during alcohol withdrawal. All patients had elevated transaminases and steatosis at liver biopsy and were withdrawn from alcohol 51 +/- 15 h (mean +/- SD) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of clonidine, 150 micrograms. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r = -0.63, p < 0.025). After clonidine administration, the decrease in plasma norepinephrine correlated with the norepinephrine basal value (r = 0.889, p < 0.001), and splanchnic oxygen extraction increased (from 40 +/- 15 to 49 +/- 17%, p < 0.025). After clonidine administration, splanchnic oxygen extraction was correlated with the decrease in plasma norepinephrine (r = 0.72, p < 0.01). Arterial lactate concentration decreased (from 0.74 +/- 0.20 to 0.64 +/- 0.23 mmol/l, p < 0.01). These results suggest that defective liver oxygen extraction might occur during alcohol withdrawal as a result of sympathetic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be controlled by pharmacological manipulation.

Adult↗
PubMed1994

Blunted systemic, splanchnic, and renal hemodynamic responses to atrial natriuretic peptide in rats with cirrhosis.

Systemic, splanchnic and renal hemodynamic responses to saline, physiological (25 ng.kg-1.min-1) and pharmacological (100, 300 and 600 ng.kg-1.min-1) doses of alpha human atrial natriuretic peptide were measured in normal (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide) and cirrhotic (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide), conscious, unrestrained rats. In addition, plasma norepinephrine concentrations were measured in normal and cirrhotic rats, before and following a 300-ng.kg-1.min-1 dose of atrial natriuretic peptide. In cirrhotic rats, splanchnic, renal and systemic hemodynamics were not significantly affected by either physiological or pharmacological doses of atrial natriuretic peptide. In normal rats, a 300 ng.kg-1.min-1 dose of atrial natriuretic peptide significantly decreased cardiac index, portal tributary blood flow and renal blood flow, and significantly increased vascular resistance in the systemic, portal, and renal territories. The other doses of atrial natriuretic peptide did not significantly change regional and systemic hemodynamics. Atrial natriuretic peptide-induced changes in plasma norepinephrine concentrations were significantly higher in normal than in cirrhotic rats (1827 +/- 834 vs. 59 +/- 46 pg/ml, mean +/- S.E., respectively). In conclusion, this study shows that the normal cardiovascular response to a 300 ng.kg-1.min-1 atrial natriuretic peptide infusion is blunted in cirrhotic rats. Moreover, in cirrhotic rats, blunting of vasoconstriction following atrial natriuretic peptide administration seems to be due to a lack of increased sympathetic vascular tone.

Animals↗
PubMed1994

Hemodynamic effects of acute administration of furosemide in patients with cirrhosis receiving beta-adrenergic antagonists.

In patients with cirrhosis, both beta-blockers and diuretics decrease the degree of portal hypertension. Since their mechanisms of action differ, the combination of these two substances should induce a more pronounced effect on portal pressure than one of these substances alone. Thus, the hemodynamic effects of furosemide were evaluated in ten patients with cirrhosis receiving beta-blockers. One hour after furosemide (0.75 mg/kg intravenously) administration, cardiac output decreased significantly from 6.2 +/- 0.6 to 5.2 +/- 0.3 l/min and blood volume from 8.0 +/- 1.6 to 5.3 +/- 0.5 l. Mean arterial pressure was not affected. Wedged and free hepatic venous pressures did not change significantly; nor did the hepatic venous pressure gradient (19.6 +/- 1.7 to 18.6 +/- 1.5 mmHg). Azygos blood flow was not affected (0.46 +/- 0.05 to 0.50 +/- 0.07 l/min). In conclusion, this study did not demonstrate that the addition of furosemide to propranolol further decreased portal pressure in patients with cirrhosis. The long-term effects of this combination are unknown and should be tested.

Adrenergic beta-Antagonists↗
PubMed1994

Hemodynamic responses to selective blockade of beta 2- and beta 1-adrenoceptors in conscious rats with cirrhosis.

This study examined the hemodynamic effects of selective beta 2-adrenergic blockade (ICI 118,551, 100 micrograms/kg intravenous (i.v.)), selective beta 1-blockade (atenolol, 2 mg i.v.) and nonselective beta-blockade (propranolol, 2 mg i.v.) in conscious rats with cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed before and following drug administration. ICI 118,551 significantly decreased portal tributary blood flow (21%), portal pressure (4%) and cardiac index (12%). Portal tributary blood flow decreases were significantly more marked than changes in cardiac index. Atenolol significantly decreased portal tributary blood flow (27%), portal pressure (15%), cardiac index (17%) and arterial pressure (7%). Propranolol significantly decreased portal tributary blood flow (37%), portal pressure (17%), cardiac index (30%), and arterial pressure (9%). Portal tributary blood flow decreases due to ICI 118,551, but not those due to atenolol, were significantly less marked than the decreases caused by propranolol. ICI 118,551- and atenolol-induced cardiac index decreases were significantly less marked than propranolol-induced decreases. In conclusion, in rats with cirrhosis, selective beta 2-blockade reduces portal pressure and portal tributary blood flow mainly by a direct effect on splanchnic vessels. This portal hypotensive action, however, was slight. Propranolol decreases portal tributary blood flow by the combination, but not the summation, of its beta 1- and beta 2-blocking effects.

Adrenergic beta-Antagonists↗
PubMed1994

Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats.

1. The effects of the sulphonylurea, glibenclamide (20 mg kg-1, i.v.), at a dose that blocks vascular potassium channels, on systemic and splanchnic haemodynamics (radioactive microspheres) were studied in conscious rats. 2. Glibenclamide significantly decreased cardiac index and hepatic artery blood flow while it significantly increased vascular resistance in systemic, portal and hepatic arterial territories. 3. In rats with suppressed cardiovascular reflexes, glibenclamide induced vasoconstriction in systemic, portal and hepatic arterial territories. 4. Intracerebroventricular administration of glibenclamide did not alter systemic or regional vascular tone. 5. Glibenclamide blunted the vasodilator effect of the potassium channel opener, diazoxide but not that of the L-type calcium channel blocker, nicardipine. 6. Another sulphonylurea, glipizide (20 mg kg-1, i.v.), induced significant systemic and splanchnic vasoconstriction. 7. Thus, the glibenclamide-induced blockade of vascular potassium channels caused a vasoconstriction in the systemic and splanchnic vascular beds. In these territories, therefore, the opening of glibenclamide-sensitive potassium channels might be responsible for a basal vasodilator tone.

Animals↗