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Biomedical subjects

G Pomier-Layrargues

Publications and source records attributed to G Pomier-Layrargues.

At least 37 records · Page 2Linked to original sources
PubMed1996

Changes in plasma endothelin-1 and Big endothelin-1 induced by transjugular intrahepatic portosystemic shunts in patients with cirrhosis and refractory ascites.

BACKGROUND/AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor that may be involved in the pathogenesis of splanchnic and renal hemodynamic changes associated with portal hypertension. The aim of this study was to measure the concentration of ET-1 and of its precursor Big endothelin-1 (Big ET-1) in the systemic circulation as well as in the splanchnic and renal venous beds and to evaluate changes after the relief of portal hypertension following transjugular intrahepatic portosystemic shunt placement. METHODS: Plasma concentrations of ET-1 and of Big ET-1 were measured in the vena cava, renal vein, hepatic vein and portal vein in ten patients with cirrhosis and refractory ascites before and 1-2 months after transjugular intrahepatic portosystemic shunt. The porto-caval gradient, creatinine clearance, plasma aldosterone and renin activity, as well as daily urinary sodium excretion were measured at the same time. RESULTS: The plasma concentration of ET-1 and Big ET-1, respectively, in peripheral blood of normal volunteers were 0.28 +/- 03 and 3.95 +/- 0.34 pg/ml; the concentrations of both peptides were higher in patients with cirrhosis, both in vena cava (0.61 +/- 0.14 and 10.01 +/- 1.47 pg/ml), hepatic vein (0.62 +/- 0.13 and 13.93 +/- 1.77 pg/ml), portal vein (1.21 +/- 0.12 and 17.84 +/- 1.98 pg/ml) and renal vein (0.76 +/- 0.12 and 14.21 +/- 1.55 pg/ml). Moreover ET-1 and Big ET-1 concentrations were more elevated in the portal vein than in the vena cava (+98% and +70%) and slightly higher in the renal vein as compared to the vena cava (+25% and +42%). After transjugular intrahepatic portosystemic shunt, a rise in creatinine clearance and urinary sodium excretion (+49%; and +53%) was observed together with a marked reduction in plasma aldosterone and renin activity (-59% and -49%). ET-1 and Big ET-1 concentrations remained unchanged in the vena cava whereas a significant reduction of ET-1 and Big ET-1 occurred both in the portal vein (-43% and -44%) and in the renal vein (-53% and -29%). Portal vein and renal vein concentrations of both peptides became similar to vena cava levels. CONCLUSIONS: Splanchnic and renal hemodynamic changes occurring in patients with cirrhosis and refractory ascites could be related to the production of ET-1 by splanchnic and renal vascular beds. This was abolished by transjugular intrahepatic portosystemic shunt, which could explain the exacerbation of systemic vasodilation and the improvement in renal perfusion observed after the procedure.

Aged↗
PubMed1996

TIPS and hepatic encephalopathy.

The increasing use of TIPS in the treatment of complications of portal hypertension has to be reassessed, taking into account the substantial collective experience gained in many centers around the world. Specific indications need to be demonstrated using well-designed clinical trials, as it is now known that (contrary to the initial expectations), the true rate of post-TIPS encephalopathy is significant and likely to be similar to that observed shortly after shunt surgery. In many patients, the decreased incidence of post-TIPS HE observed during follow-up is related to progressive stenosis of the shunt. This is associated with the recurrence of portal hypertension and, often, with the onset of clinical complications such as ascites or variceal bleeding. Prospective studies are required to define the ideal compromise between portal decompression and maintenance of a certain amount of portal perfusion to the liver and, thus, some portal hypertension, but at a threshold level below that associated with an increased risk of clinical complications. TIPS must be regarded as only one of several therapeutic modalities available to treat portal hypertension. When TIPS induces disabling encephalopathy or accelerated liver failure, closure of the shunt should be performed early, and alternative treatments can be used, including endoscopic sclerotherapy, variceal ligation, large volume paracentesis, and, most importantly, liver transplantation. Hopefully, lessons from the past gleaned from the evaluation of surgical portacaval shunts in the treatment of portal hypertension will help to better define the appropriate use of TIPS in cirrhotic patients to maximize the beneficial effects of reducing the portal pressure while minimizing the deleterious effects of this procedure.

Clinical Trials as Topic↗
PubMed1996

Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

BACKGROUND: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE. AIMS: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease. PATIENTS: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study. METHODS: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement). RESULTS: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated. CONCLUSIONS: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.

Chronic Disease↗
PubMed1996

Haemodynamic adaptation two months after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients.

BACKGROUND AND AIMS: In portal hypertensive patients, transjugular intrahepatic portosystemic shunt (TIPS) acutely increases cardiac output and exaggerates peripheral vasodilatation. It has been suggested that the worsened hyperdynamic state may progress to high output heart failure. The aim was to evaluate the acute and short-term haemodynamic adaptation to this procedure. METHODS: Systemic, splanchnic, and pulmonary haemodynamics were studied in 15 cirrhotic patients under stable haemodynamic conditions before placement of TIPS, then 15-30 minutes after and two months later. For inclusion in the final analysis, an uneventful post-TIPS at two months follow up and a stable portacaval gradient were required. The following variables were measured or calculated: portacaval gradient; cardiac index (thermodilution); systolic and diastolic mean arterial, atrial, pulmonary arterial, and wedged pulmonary capillary pressures; heart rate; and total peripheral and pulmonary vascular resistances. Blood flow in the shunt was measured using duplex Doppler ultrasound. RESULTS: The portacaval gradient decreased by 56% and remained stable thereafter. Shunt blood flow was unchanged when measured immediately after TIPS and two months later. Immediately after TIPS there was a pronounced increase in cardiac index (+32%; p < 0.05) in association with a decrease in peripheral and pulmonary vascular resistance (-21%; p < 0.05 and -14%; NS). Two months later, whereas the initial rise in cardiac index was attenuated, peripheral vascular resistances remained similar and pulmonary vascular resistances decreased further (-33%; p < 0.05) compared with immediate post-TIPS values. CONCLUSIONS: Hyperdynamic circulation worsened immediately after TIPS, with a progressive adaptation during follow up. The mechanisms of post-TIPS induced haemodynamic changes include an abrupt volume load resulting from splanchnic decompression and an increased delivery of gut derived vasodilators to the systemic circulation. The persistence of decreased peripheral and pulmonary vascular resistances despite the reduction in high cardiac output two months after TIPS suggests that vasodilatation is not solely a compensatory response to a TIPS induced increased preload. Vasodilatory substances shunted away from the liver probably play an important part in this phenomenon.

Adaptation, Physiological↗
PubMed1996

Liver blood flow in chronic hemodialysis patients.

The purpose of this study was to assess liver blood flow and cardiac output in chronic hemodialysis patients (n = 7) before and after a hemodialysis session, and to compare it to normal volunteers (n = 11). We used the hepatic clearance of sorbitol to calculate liver blood flow and echocardiograms to evaluate cardiac output. The latter was higher in hemodialysis patients (predialysis 4.7 +/- 1.8 liters/min, postdialysis 4.5 +/- 0.9 liters/min) compared to normal subjects (3.8 +/- 0.9 liters/min, p = 0.09 and p = 0.05). Hepatic blood clearance of sorbitol was similar in hemodialysis patients before and after dialysis (1,610 +/- 266 and 1,541 +/- 415 ml/min) as well as in normal volunteers (1,565 +/- 313 ml/min). The hepatic extraction ratio of sorbitol is slightly decreased in hemodialysis patients (n = 3) (0.87 +/- 0.03) compared to values reported in the literature for healthy subjects. We conclude that liver blood flow is not significantly altered in hemodialysis patients.

Adult↗
PubMed1995

Short- and long-term hemodynamic effects of transjugular intrahepatic portosystemic shunts: a Doppler/manometric correlative study.

OBJECTIVE: The purposes of this study were to evaluate the effect of a well-functioning transjugular intrahepatic portosystemic shunt (TIPS) on the splanchnic and intrahepatic circulation, to determine if sonographic measurements can predict shunt dysfunction before clinical manifestations of portal hypertension occur, and to compare Doppler sonographic findings with portocaval gradient measurements before and after shunt revision. SUBJECTS AND METHODS: Forty-four patients with cirrhosis (n = 43) and myelofibrosis (n = 1) who underwent successful TIPS insertion were included in this prospective study. Indications for TIPS placement were: refractory ascites (24 patients), bleeding esophageal varices (17 patients), portal hypertensive gastropathy (two patients), and bleeding colonic varices (one patient). The portal vein and the inferior vena cava were catheterized; and the portocaval gradient was recorded before TIPS placement, at 2 and 12 months after TIPS placement, and when clinical or Doppler findings suggested shunt dysfunction. Doppler studies were done within 1 week before TIPS placement, within 2 days after TIPS placement, every 2-3 months thereafter, and before and after a TIPS revision. The Doppler studies included flow volume measurements in the portal vein and in the stent, as well as determination of the direction of flow in the segmental branches of the portal vein, in the splanchnic veins, and in portosystemic collaterals. Changes in Doppler findings and in catheter pressure measurements were compared using Spearman's rank correlation test. Significance was set at the .05 level. RESULTS: A marked decrease (-51%) in portocaval gradient was observed after TIPS placement. At Doppler sonography, portal vein velocity and diameter were both higher after TIPS placement, resulting in a marked increase in portal venous flow (170%). Mean flow velocity in the shunt was 55.8 +/- 3.6 cm/sec, and flow volumes in the shunt and in the main portal vein were 1596 ml/min and 1731 ml/min, respectively (p = nonsignificant). Dysfunction of the stent occurred in 27% of the patients. Changes in stent blood flow volume were closely related to changes in the portocaval gradient (r = -0.67, p < .001). Reduction of blood flow volume in the stent or change of direction of flow in intrahepatic portal veins or in collateral veins signaled shunt dysfunction (84% sensitivity, 89% specificity). CONCLUSION: Marked hemodynamic changes in the portal venous system occur soon after a TIPS procedure. Monitoring of shunt function with periodic Doppler sonography, including calculation of shunt blood flow, is useful in detecting shunt dysfunction before clinical signs occur.

Adult↗
PubMed1995

Improvement of hepatorenal syndrome by transjugular intrahepatic portosystemic shunt.

Hepatorenal syndrome (HRS) is a functional renal failure occurring in advanced liver cirrhosis with ascites. It is due to renal cortical vasoconstriction resulting from complex hemodynamic disturbances related to cirrhosis and portal hypertension. There is no consistently effective therapy except for liver transplantation. We report a case of severe HRS in a patient with advanced liver cirrhosis and portal hypertension. Three sessions of hemodialysis were performed because of severe renal failure (serum urea 83 mg/dl, serum creatinine 6 mg/dl). Creation of an intrahepatic portosystemic shunt reduced the portocaval gradient from 18 to 7 mm Hg. Spectacular improvement of the renal function was observed soon after the procedure, with spontaneous recovery of diuresis and a return of serum urea and creatinine to baseline values. The patient unfortunately died 2 months later from adult respiratory distress syndrome post emergency surgery for a massive bleed related to a duodenal ulcer. Throughout this episode, the renal function remained stable. The postmortem examination showed histologically normal kidneys. We conclude that the intrahepatic portosystemic shunt can improve renal function in cirrhotic patients with HRS; it could be used in patients awaiting liver transplantation to reverse preoperative renal failure.

Hepatorenal Syndrome↗
PubMed1994

Meal induced changes in hepatic and splanchnic circulation: a noninvasive Doppler study in normal humans.

The haemodynamic effects of a meal on the splanchnic and hepatic circulation were evaluated in 30 healthy volunteers, using Doppler ultrasonography. The resistance index (RI) of the superior mesenteric artery and of the left and right intrahepatic arteries, the portal vein blood flow as well as the ratio between maximal velocity in the left and right intrahepatic arteries and the adjacent portal vein were measured initially, then 15, 30, 45, and 60 min after the ingestion of a standard balanced liquid meal. Postprandial haemodynamic changes were maximal 30 min after the meal; at that time, mesenteric artery RI decreased significantly [mean -11% (SEM 14%)] whereas portal vein blood flow increased markedly [mean +79% (SEM 14%)]; a significant increase in hepatic artery RI was observed in both liver lobes. The ratio between maximal velocities of the intrahepatic artery and the intrahepatic portal vein was reduced significantly; this ratio decreased more markedly in the right lobe of the liver. These findings would suggest that there was an adaptation of hepatic artery to portal vein blood flow after a meal. The subsequent increase in intrahepatic portal vein flow velocity was found to be greater in the right lobe of the liver.

Adult↗
PubMed1994

Transhepatic portal vein stenting for treatment of ruptured duodenopancreatic varices in a patient with chronic pancreatitis.

BACKGROUND: Portal vein obstruction with secondary variceal bleeding in the setting of chronic pancreatitis has not been recognized as frequently as splenic vein occlusion. This condition can be difficult to diagnose and treat. METHODS: A 54-year old man was referred for massive recurrent endoscopy-negative upper-gastrointestinal bleeding. The diagnosis of duodenopancreatic varices was finally made. Direct portography showed a high-grade stenosis of the proximal portal vein that was dilated and stented with a balloon expandable prosthesis. RESULTS: The gradient across the stenosis fell from 9 to 2 mm Hg. Bleeding stopped. After 7 months of follow-up, the patient has experienced no rebleeding, and a Doppler examination is normal. CONCLUSIONS: In patients with chronic pancreatitis and upper gastrointestinal tract bleeding of unknown origin, obstruction of one of the major splanchnic veins must be excluded. Portal vein dilatation and stenting appears to be a safe procedure with good short-term results.

Angioplasty, Balloon↗
PubMed1994

Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial.

Previous reports have suggested that "endogenous" benzodiazepines could contribute to neural inhibition in hepatic encephalopathy. RO 15-1788 (flumazenil), a specific antagonist of brain benzodiazepine receptors, could thus reverse the neurological symptoms of hepatic encephalopathy. To test this possibility, we conducted a double-blind, placebo-controlled crossover trial of the efficacy of flumazenil in cirrhotic patients in hepatic coma. Seventy-seven cirrhotic patients in hepatic coma were evaluated. Fifty-six were excluded from the trial because of multiorgan failure or because coma was precipitated by prior use of benzodiazepines, and 21 patients were randomly assigned to the flumazenil group (11 patients) or the placebo group (10 patients). Treatment was administered intravenously as a 20-ml solution (placebo or 2 mg flumazenil); seven patients were crossed over. Clinical status was assessed blindly by two observers, using a modified Glasgow scale, every 15 min for 6 hr. Electroencephalogram tracings obtained before and after drug administration were evaluated blindly by two independent observers. Serum concentrations of benzodiazepines before treatment were measured by means of a fluorescence polarization immunoassay. Improvement in neurological symptoms was observed in six patients treated with flumazenil, whereas none in the placebo group showed improvement (p < 0.05; Fisher's exact test). Improvements in electroencephalogram tracings were demonstrated in four patients treated with flumazenil, compared with two patients in the placebo group (p = NS). Benzodiazepines were found in the serum of four patients treated with flumazenil (two responders and two nonresponders); all of these patients had received pharmaceutical benzodiazepines 4 to 6 days before the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Hepatic artery: effect of a meal in healthy persons and transplant recipients.

Thirty healthy volunteers and 12 liver allograft recipients (two with cirrhotic changes seen at microscopy) were given a standard meal. Doppler sonography of the right and left hepatic arteries, the superior mesenteric artery, and the portal vein was performed. The change in hepatic arterial resistance was evaluated with the resistive index (RI). After the standard meal, portal venous flow increased in both the healthy volunteers and allograft recipients (more so in the latter group). Superior mesenteric arterial RI decreased in all subjects. A postprandial increase in hepatic arterial RI, likely reflecting constriction of the hepatic artery, was seen in both groups. It was absent in the two patients with recurrent transplant cirrhosis. These results show the importance of examining hepatic arterial flow in the fasting subject, since high resistance after a meal may be falsely interpreted as a sign of disease. Absence of a postprandial change in resistance of the hepatic artery could signal abnormal liver function.

Adult↗
PubMed1993

Portal hypertension in lymphoproliferative and myeloproliferative disorders: hemodynamic and histological correlations.

The pathogenesis of portal hypertension in patients with lymphoproliferative and myeloproliferative disorders is not fully understood. We investigated 20 patients with myeloproliferative disease and 47 patients with lymphoproliferative disease. Transvenous liver biopsies and hepatic vein pressure gradient measurements were performed in all patients, and portal vein blood flow was measured by pulsed Doppler sonography in 31 of these patients and in 22 normal volunteers. The hepatic vein pressure gradient was significantly higher in patients with hepatic infiltrates, fibrosis or both than in patients without hepatic lesions (8.3 +/- 5.0 mmHg vs. 4.1 +/- 2.3 mmHg; p < 0.01). Portal vein blood flow was significantly higher in patients with hematological disease than in normal volunteers (31.2 +/- 15.5 ml/min.kg vs. 14.2 +/- 4.6 ml/min.kg;p < 0.01). In 81.8% of patients with hepatic infiltrates, fibrosis or both and increased portal vein blood flow, the hepatic vein pressure gradient was greater than 6 mm Hg. Although we saw a significant correlation between splenic vein blood flow and portal vein blood flow (n = 20; p < 0.01), we found no significant correlation between splenic vein blood flow and hepatic vein pressure gradient or spleen size. Hepatic infiltration and fibrosis appear to be major determinants of increased hepatic vein pressure gradient, probably because they increase intrahepatic vascular resistance. The role of increased splenic blood flow is probably not determinant. However, because portal pressure was not measured directly in this study, the incidence of portal hypertension may have been underestimated.

Adult↗
PubMed1992

Combined treatment of portal hypertension with ritanserin and propranolol in conscious and unrestrained cirrhotic rats.

We recently reported that ritanserin, a 5-hydroxytryptamine receptor antagonist, induced significant reduction of portal pressure in cirrhotic rats. In this study, we investigated the hemodynamic effects of a combination of propranolol and ritanserin in conscious and unrestrained cirrhotic rats. Heparinized catheters exiting from the neck were placed into the portal vein, inferior vena cava, aorta and left ventricle. Cardiac output and regional blood flows were measured with radiolabeled microspheres and the reference-sample method. Serial hemodynamic studies were performed 4 hr after rats awakened (basal), 1 hr after administration of ritanserin (0.63 mg/kg body wt, intravenously) and after intravenous propranolol infusion (0.33 mg/kg/min for 15 min) in nine cirrhotic rats. Similar measurements were obtained in a control group of eight cirrhotic rats treated with the solvents of ritanserin and propranolol. Ritanserin caused significant reduction of portal pressure (-19%). Portal-venous inflow and splanchnic arteriolar resistances remained unchanged, whereas portal-venous resistances were slightly but significantly lowered (-17%); and ritanserin had no effects on systemic hemodynamics. The addition of propranolol resulted in further reduction of portal pressure (-24%); the final reduction after combined therapy was -38%. Propranolol induced a marked decrease in cardiac output (-31%) and portal-venous inflow (-30%). It also caused a significant increase in splanchnic arteriolar resistance (+39%), but did not magnify the ritanserin-induced decrease of portal-venous resistance. The combined therapy did not modify the mean arterial pressure. Our results show that the effects of ritanserin on portal pressure--probably mediated by a reduction of intrahepatic and/or portocollateral resistances--can be potentiated by propranolol, which lowers the portal-venous inflow.

Animals↗
PubMed1992

Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension.

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n = 13) or portal vein ligation (n = 13). 2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group. 3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (-18%) in cirrhotic rats, but not in portal-vein-ligated rats. 4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.

Animals↗