Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

At least 145 records · Page 8Linked to original sources

PubMed1993

Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension.

Although prostaglandins are thought to be involved in the hyperdynamic circulation of portal hypertension, the role of this substance has not been elucidated. Dose-response curves, the hemodynamic effects of prostacyclin (20 micrograms/kg) and its inhibitor indomethacin and measurements of plasma and urinary levels of 6-keto-prostaglandin F1 alpha were compared in three groups of six rats each: normal, with portal vein stenosis and with secondary biliary cirrhosis. Plasma and urinary levels of 6-keto-prostaglandin F1 alpha were higher in rats with portal vein stenosis and cirrhotic rats than in normal rats. Dose-response curves showed similar maximal decreases in arterial pressure in the three groups, whereas the maximal increase in portal pressure was less marked in cirrhotic rats than in normal rats and rats with portal vein stenosis. In normal rats, prostacyclin increased cardiac output by 21% and portal pressure by 41%. Similar increases were observed in rats with portal vein stenosis. In contrast, prostacyclin did not affect cardiac output and portal pressure in cirrhotic rats. Indomethacin induced a more marked vasoconstrictive effect in normal rats than in cirrhotic rats. This study shows that prostacyclin plays a role in the hemodynamic alterations in portal hypertension. Moreover, the hyporeactivity observed in cirrhotic rats suggests that prostacyclin plays a major role in the circulatory changes of portal hypertension due to chronic liver disease.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Persistence of systemic and splanchnic hyperkinetic circulation in liver transplant patients.

Portal pressure and portal-systemic collateral circulation after orthotopic liver transplantation have not been investigated. We studied systemic and splanchnic hemodynamics in 17 patients with cirrhosis before and 205 +/- 146 days after orthotopic liver transplantation. Among the 17 orthotopic liver transplantation patients, 12 had undergone hemodynamic study in the 6 mo before orthotopic liver transplantation. Controls were 50 patients with normal liver architecture. Cardiac index remained elevated in orthotopic liver transplantation patients compared with controls (3.6 +/- 0.9 vs 3.1 +/- 0.4 L/min.m2; p < 0.05). Azygos blood flow, which was elevated before orthotopic liver transplantation (585 +/- 402 ml/min), remained elevated after orthotopic liver transplantation (553 +/- 343 ml/min). In transplant patients, hepatic blood flow was higher than it was in controls (2.26 +/- 0.86 vs. 1.38 +/- 0.57 L/min; p < 0.05). Elevated hepatic blood flow correlated with cardiac index (r = 0.647, p < 0.025). In patients with normal graft function, hepatic venous pressure gradient was normal (2 +/- 1 mm Hg). In a patient with acute rejection, a sharp elevation in the hepatic venous pressure gradient was observed; it returned to normal 45 days after treatment. We conclude that despite normal portal pressure, portal-systemic collateral blood flow remains elevated after orthotopic liver transplantation. Possibly because of persistent collateral circulation, which may keep portal tributary blood flow elevated, hepatic blood flow is increased after orthotopic liver transplantation. Elevated splanchnic blood flow, in turn, contributes to the high cardiac index in liver recipients. Finally, a sharp elevation in portal pressure, which may be observed during acute rejection and subsides after treatment, merits further study.

Adult↗

PubMed1992

Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment.

OBJECTIVE: To assess the effectiveness of beta-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. DATA SOURCES: Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. STUDY SELECTION: Randomized trials comparing beta-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of beta-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of sclerotherapy were published as full papers. DATA EXTRACTION: Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. DATA SYNTHESIS: The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of beta-blockers was significantly reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. CONCLUSIONS: Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.

Adrenergic beta-Antagonists↗

PubMed1992

Pharmacokinetics of lomefloxacin in patients with cirrhosis.

The effect of liver failure on the pharmacokinetics of lomefloxacin was studied in 12 patients with cirrhosis. Patients received a single oral dose of 400 mg lomefloxacin, and blood and urine samples were collected at intervals over the next 48 hours. The concentrations of lomefloxacin in all samples were measured using high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) maximum plasma concentration (Cmax) in these patients was 3.9 +/- 1.20 micrograms/mL. The mean time to maximum serum concentration (Tmax) was 2.1 +/- 2.6 hours, and the mean elimination half-life (t1/2) was 9.16 +/- 1.93 hours. Mean renal clearance was 88.9 +/- 38.0 mL/min/1.73 m2, and the mean nonrenal clearance was 61.6 +/- 19.0 mL/min/1.73 m2, which corresponded to 41% of the total body clearance. No correlations were observed between nonrenal clearance and hepatic insufficiency (Pugh score) or nonrenal clearance and plasma bilirubin. These results show that liver failure does not per se affect lomefloxacin kinetics. Thus, no adjustments in lomefloxacin dosages appear to be necessary for patients with impaired liver function tests.

Adult↗

PubMed1992

Plasma catecholamine concentrations are a reliable index of sympathetic vascular tone in patients with cirrhosis.

In patients with cirrhosis, the significance of elevated plasma catecholamine concentrations is unclear. Thus we investigated the relationship between plasma catecholamine concentrations and the hemodynamic effect of pindolol (an index of sympathetic vascular tone) in 10 patients with cirrhosis. Systemic and splanchnic hemodynamics and plasma catecholamine concentrations in the pulmonary artery and the splanchnic veins (hepatic and azygos veins) were studied before and after the oral administration of pindolol (20 mg). In basal conditions patients exhibited a hyperkinetic circulatory syndrome and elevated plasma catecholamine concentrations. Alterations in basal hemodynamics were correlated with plasma epinephrine concentrations but not with norepinephrine. Pindolol administration significantly decreased heart rate and increased right atrial pressure. After pindolol administration, individual hemodynamic changes (cardiac index, systemic vascular resistance, wedged hepatic venous pressure) were significantly correlated with plasma catecholamine concentrations. In conclusion, this study shows that in cirrhotic patients epinephrine may play a role in hemodynamic alterations, and plasma catecholamine concentrations are an index of sympathetic vascular tone.

Epinephrine↗

PubMed1992

Circulatory changes induced by portal venous diversion and mesenteric hypertension in rats.

We studied the hemodynamics in four groups of rats with combinations of mesenteric hypertension and portal diversion. Operations created three groups with mesenteric hypertension and different degrees of portal venous diversion: mesenteric vein stenosis, portal vein stenosis and end-to-side portacaval anastomosis with mesenteric vein stenosis, the fourth group had only portacaval anastomosis. A control group had sham operations. Cardiac output, splanchnic blood flows and portosystemic shunt indices were measured with radioactive microspheres. Mesenteric venous pressures in the mesenteric-stenosed, portal-stenosed, portacaval-shunted and end-to-side portacaval anastomosis with mesenteric vein stenosis rats were, respectively, 13.5 +/- 0.6, 15.3 +/- 0.7, 4.3 +/- 0.5 and 13.0 +/- 0.9 mm Hg, which were all significantly different from controls: 8.3 +/- 0.3 mm Hg. Portosystemic shunt indices were also significantly different from each other: controls, 0.4% +/- 0.02%; mesenteric-stenosed, 5.9% +/- 2.3%; and portal-stenosed, 52.1% +/- 4.9%. Cardiac output and splanchnic visceral blood flows were significantly increased in the portal-stenosed rats and the two groups with portacaval anastomoses, with the latter two groups having the highest values. The addition of mesenteric stenosis did not change the blood flows because mesenteric-stenosed rats did not differ from controls and end-to-side portacaval anastomosis with mesenteric vein stenosis rats did not differ from rats with portacaval anastomosis alone. These results suggest that mesenteric venous hypertension per se does not affect hemodynamics but that diversion of portal venous blood from the liver is a critical factor in the development of hyperkinetic circulation in portal hypertension.

Abdomen↗

PubMed1992

Hemodynamic effects of terbutaline, a beta 2-adrenoceptor agonist, in conscious rats with secondary biliary cirrhosis.

The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor agonist - were studied in conscious normal rats and in conscious rats with secondary biliary cirrhosis. Compared with those of normal rats, dose-response curves in cirrhotic rats indicated significantly decreased reactivity in arterial pressure and heart rate. Half-maximal effective dose was not significantly different between the two groups. Terbutaline induced significant, dose-dependent decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1 body wt) increased both cardiac output and portal tributary blood flow, thus mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to 22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The association of a decreased portal pressure and increased splanchnic blood flow suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal collateral vascular resistance.

Adrenergic beta-Agonists↗

PubMed1992

Total effective vascular compliance in patients with cirrhosis: a study of the response to acute blood volume expansion.

Although arterial vasodilation is a well-known feature in patients with cirrhosis, the venous system remains unexplored. To measure total effective vascular compliance, a reflection of the properties of the venous system, rapid volume expansion (300 ml of a gelatin solution in 3 min) was performed in 23 patients. Eleven patients had compensated cirrhosis (Child-Pugh grade A or B), and eight had decompensated cirrhosis (Child-Pugh grade C). Four control patients had mild chronic hepatitis, normal hepatic venous pressure and normal liver architecture. Cardiac index, hepatic venous pressures, hepatic and azygos blood flow and renal plasma flow were measured before and immediately after volume expansion. Right atrial pressure was recorded during volume expansion. This allowed the calculation of total effective vascular compliance, which was higher in patients with decompensated cirrhosis than in those with compensated cirrhosis (4.65 +/- 4.21 vs. 1.34 +/- 0.63 ml.mm Hg-1.kg-1; p less than 0.05). In response to volume expansion, renal vascular resistance decreased significantly in patients with compensated cirrhosis, but not in those with decompensated cirrhosis (-30% +/- 33% vs. +2% +/- 23%; p less than 0.05). No change was seen in glomerular filtration rate. Systemic oxygen consumption increased in patients with compensated cirrhosis, but not in those patients with decompensated cirrhosis (25% +/- 33% vs. -4% +/- 9%; p less than 0.05). Although in all patients with cirrhosis volume expansion increased central venous pressures, azygos blood flow and the hepatic venous pressure gradient did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Evidence for normal nitric oxide-mediated vasodilator tone in conscious rats with cirrhosis.

Because it has been hypothesized that the hyperkinetic circulation in portal hypertension is the result of increased synthesis of nitric oxide, we compared the hemodynamic effects of nitric oxide synthesis--specific agonist (L-arginine) and antagonist between normal and cirrhotic conscious rats. The dose-response curves showed that L-arginine significantly decreased arterial pressure and increased heart rate. These changes started at the 200 mg/kg dose and were similar in both groups of rats. In both groups of rats NG-monomethyl-L-arginine (25 mg/kg) significantly decreased cardiac output by 35%. In cirrhotic rats, NG-monomethyl-L-arginine decreased portal pressure from 15.3 +/- 0.9 mm Hg to 13.6 +/- 0.7 mm Hg and portal tributary blood flow from 7.8 +/- 0.7 ml.min-1.100 gm-1 to 5.9 +/- 0.7 ml.min-1.100 gm-1; it significantly increased portal territory vascular resistance from 950 +/- 108 dyn.sec.cm-5.100 gm-1 x 10(3) to 1,579 +/- 258 dyn.sec.cm-5.100 gm-1 x 10(3). In normal rats, portal tributary blood flow decreased similarly, by 27%, and portal territory vascular resistance increased by 55%. In neither group was hepatic arterial blood flow altered. Before and after NG-monomethyl-L-arginine administration, arterial cyclic GMP concentrations were not significantly different between normal and cirrhotic rats. In conclusion, this study shows evidence of a normal role for nitric oxide-mediated vasodilatation in rats with cirrhosis and that inhibition of nitric oxide synthesis reduces portal hypertension. These results did not support the hypothesis that nitric oxide synthesis is increased in cirrhosis.

Animals↗

PubMed1992

Hemodynamic effects of calibrated stenosis of the superior mesenteric artery in conscious rats with portal vein stenosis.

Because superior mesenteric arterial blood flow is increased in portal hypertension and plays a role in elevated portal pressure, mechanical reduction of artery diameter should induce decreases in portal pressure and superior mesenteric arterial blood flow. In this study, calibrated superior mesenteric artery stenosis (induced with a 22-gauge needle) was performed in rats simultaneously with portal vein stenosis or 2 wk after creation of portal vein stenosis. Hemodynamic studies were performed 3 wk after induction of portal vein stenosis in conscious, unrestrained rats. At that time, neither weight loss nor digestive tract alterations were observed in rats with arterial stenosis. In neither group of rats with arterial stenosis was portal tributary blood flow significantly different from that of normal rats; nor was it significantly lower than in rats with portal vein stenosis without arterial stenosis. In both groups of rats with arterial stenosis, portal pressure was significantly lower (12.1 +/- 1.6 mm Hg and 12.5 +/- 1.8 mm Hg, respectively) than in rats subjected to portal vein stenosis (15.4 +/- 1.5 mm Hg) but significantly higher than in controls (7.2 +/- 1.0 mm Hg). In rats with arterial stenosis, cardiac index was also significantly lower than that in rats with portal vein stenosis but higher than that in controls. In conclusion, this study shows that both early and late superior mesenteric artery stenosis significantly reduce the degree of portal hypertension and the hyperkinetic state of rats with extrahepatic portal hypertension. Thus we can speculate that superior mesenteric artery stenosis might provide a new therapeutic approach for portal hypertension.

Analysis of Variance↗

PubMed1992

Persistence of a hyperdynamic circulation in cirrhotic rats following removal of the sympathetic nervous system.

The sympathetic nervous system is thought to play a role in the pathogenesis of the hyperdynamic circulation associated with portal hypertension. However, the extent of this role is unknown. After elimination of all neurological control by pithing, systemic and regional hemodynamics were studied in rats with portal hypertension caused by either portal vein stenosis or biliary cirrhosis. In normal rats, pithing induced a two-thirds decrease in mean arterial pressure and cardiac index. Compared with pithed normal rats, pithed portal vein-stenosed rats showed similar values for mean arterial pressure, cardiac index, and portal tributary blood flow. In contrast, pithed cirrhotic rats still showed hyperdynamic circulation with increased cardiac index and portal tributary blood flow. Although pithing dramatically reduced portal pressure in all groups, portal pressure remained significantly higher in portal hypertensive rats than in normal rats. These results indicate that in rats with portal vein stenosis, the sympathetic nervous system plays a major role in hemodynamic alterations, whereas in rats with cirrhosis, nonneurogenic factors participate in the pathogenesis of the hyperdynamic circulation.

Animals↗

PubMed1992

Hemodynamic, neurohumoral, and metabolic responses to amino acid infusion in patients with cirrhosis.

In patients with cirrhosis the renal response to amino acid infusion is controversial. In addition, the renal and systemic metabolic effects of amino acids are unknown. Therefore, the present study examined the effects of amino acids on renal hemodynamics, renal and systemic oxygen (O2) consumption, and hormones in patients with cirrhosis. Twelve patients received an 8% amino acid solution for 30 minutes at a rate providing 250 mg of amino acids/kg body wt. Renal blood flow increased by 45% (P less than 0.05) and the glomerular filtration rate by only 9% (P greater than 0.05). Renal vascular resistance decreased by 23% (P less than 0.05), and renal perfusion pressure did not change significantly. Renal and systemic O2 consumption and pulmonary artery plasma glucagon level significantly increased. There were no significant changes in plasma osmolality, plasma volume, and plasma atrial natriuretic peptide concentrations. In conclusion, the results show that amino acid-induced renal vasodilation caused hyperperfusion but not renal hyperfiltration in patients with cirrhosis. In addition, renal hyperemia was associated with renal and systemic hypermetabolism.

Amino Acids↗

PubMed1992

Hemodynamic effects of endotoxin and platelet activating factor in cirrhotic rats.

Acute infections may influence the hemodynamic alterations of liver disease. Therefore, the hemodynamic effects of endotoxin (LPS E. coli 0111:B4) in conscious, normal, and cirrhotic rats were compared. Endotoxin decreased cardiac index in cirrhotic but not in normal rats. Although the effect of endotoxin on portal tributary blood flow was minor in all animals, a reduction in portal pressure was found in cirrhotic rats. Because the most marked hemodynamic effects were observed in cirrhotic rats, the second part of our study investigated whether platelet activating factor played a role in endotoxin-induced hemodynamic alterations in the cirrhotic model. Platelet activating factor reduced cardiac index and kidney blood flow but did not influence portal tributary blood flow. Two antagonists to platelet activating factor reduced the adverse renal blood flow lowering effects of endotoxin in cirrhotic rats. Thus, it is suggested that the hemodynamic changes observed in cirrhosis may be aggravated during acute infections. Under this condition, antagonists to platelet activating factor may be of benefit in the prevention of hemodynamic complications induced by endotoxin.

Animals↗

PubMed1992

Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat.

Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation.

Animals↗

PubMed1992

Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis.

Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis.

Adult↗

PubMed1992

Hemodynamic and sympathetic responses to human atrial natriuretic peptide infusion in patients with cirrhosis.

To determine the potential usefulness of atrial natriuretic peptide (ANP) in patients with cirrhosis, we examined the effects of the infusion of a low dose of alpha-human ANP (alpha hANP, 25 ng.kg-1.min-1 for 30 min) on renal, splanchnic, systemic hemodynamics and sympathetic outflow in eight patients. Pulmonary arterial plasma ANP concentrations increased from 59 +/- 9 to 328 +/- 41 pg/ml (mean +/- S.E., p less than 0.05). Mean values of glomerular filtration rate and renal plasma flow were not significantly changed. Individual renal plasma flow responses differed from one patient to another. Renal plasma flow increased in two patients, decreased in three and did not change in the other patients. Renal plasma flow changes were correlated with basal renal plasma flow values (r = -0.938, p less than 0.05) but not with arterial pressure changes or renal vein plasma norepinephrine concentration changes. Azygos blood flow increased from 0.43 +/- 0.10 to 0.63 +/- 0.13 l/min (p less than 0.05) and the hepatic-venous pressure gradient decreased from 19.9 +/- 1.5 to 17.5 +/- 2.9 mmHg in post-infusion (p less than 0.05). Mean arterial pressure decreased significantly by 18% and cardiac output by 12%. Systemic vascular resistance and pulmonary arterial plasma norepinephrine concentrations were not significantly modified. Thus, in patients with cirrhosis, alpha hANP appears to have a direct vasodilating action on renal arterioles when basal renal vascular tone is high. In addition, although alpha hANP might exert a portal hypotensive action, alpha hANP induced arterial hypotension as a result of both low cardiac output and a lack of increased sympathetic vascular tone. The arterial hypotensive action may, thus, limit the therapeutic use of low doses of alpha hANP in cirrhotic patients.

Aldosterone↗

PubMed1992

Blockade of ATP-sensitive K+ channels by glibenclamide reduces portal pressure and hyperkinetic circulation in portal hypertensive rats.

Certain results of in vitro studies raise the possibility that blockade of ATP-sensitive K+ channels by glibenclamide may induce vasoconstriction. Therefore, this substance might decrease portal pressure and hyperkinetic circulation in animals with portal hypertension. Thus, systemic and regional hemodynamics (radioactive microspheres) were measured before and 20 min after a bolus intravenous injection of glibenclamide (20 mg/kg) in conscious rats with portal vein stenosis. Blood pressure decreased significantly from 14.5 +/- 1.5 to 12.2 +/- 1.2 (mean +/- SE). Cardiac index significantly decreased by 24%, portal tributary blood flow by 31%, and hepatic artery blood flow by 35%. Systemic vascular resistance significantly increased by 38%, portal territory vascular resistance and hepatic artery vascular resistance by 61%, each, and renal vascular resistance by 17%. Arterial pressure, heart rate, and renal blood flow were unchanged. Moreover, glibenclamide blunted the vasodilating action of diazoxide (an ATP-sensitive K+ channel opener). These results show that in rats with extrahepatic portal hypertension the blockade of ATP-sensitive K+ channels by glibenclamide reduces portal pressure and hyperkinetic circulation.

Adenosine Triphosphate↗

PubMed1992

[Effects of halogenated anesthetics on splanchnic hemodynamic in normo- and hypovolemic cirrhotic rats].

The effects of 1 MAC of either halothane, enflurane or isoflurane on splanchnic haemodynamics were studied in cirrhotic rats that were either normovolaemic or hypovolaemic from haemorrhage. A group of conscious rats acted as the control group. Bile duct ligation had been carried out in all the rats four weeks previously to induce cirrhosis. At the time of the study, all the rats were anaesthetized with ether for catheterization of the left femoral artery and vein, and the left ventricle via the right carotid. The control group was allowed to awake. When the other rats started to recover, they were artificially ventilated with room air and 1 MAC of the halogenated agent. Heart rate and mean arterial blood pressure were monitored continuously. Once the animals had remained steady for one hour, 1.25 ml of blood for 100 g body weight was removed over a 10 min period. PaO2, PaCO2, arterial pH, heart rate, mean arterial blood pressure, cardiac index and regional blood flows (RBF) were measured before, and thirty minutes after the haemorrhage. Cardiac output and RBF were measured using the radioactive-labelled microsphere method. Only 32 animals were finally included, eight in each group. Splanchnic, portal and hepatic arterial blood flows were similar in conscious rats and in those receiving isoflurane or halothane, and were higher than in those receiving enflurane. The lowest splanchnic and portal venous blood flows were found in those rats receiving enflurane. After haemorrhage, these RBF decreased significantly in all groups except in the enflurane group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗