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Biomedical subjects

D Lebrec

Publications and source records attributed to D Lebrec.

At least 199 records · Page 11Linked to original sources
PubMed1990

Orthotopic liver transplantation with hepatic artery anastomoses. Hemodynamics and response to hemorrhage in conscious rats.

Orthotopic liver isotransplantation was performed in one group of Lewis rats using cuffs for the portal vein and the infrahepatic vena cava, stents for the hepatic artery and the bile duct. Three other groups were also investigated: group A, normal rats; group B, sham-transplanted rats (clamping of the vessels, washing of the liver, placing cuffs around the portal vein); and group C, sham-transplanted rats with ligature section of the hepatic artery. Blood-flow measurements were performed, 1 week after the surgical procedure, with the radioactive microsphere method in conscious animals. Transplanted rats exhibited significant (ANOVA, P less than 0.05) increase in cardiac index and decrease in mean arterial pressure and systemic vascular resistance. Blood flows of the portal territory and to the kidneys were not significantly modified. Arterial liver blood flow and arterial liver vascular resistance in rats with liver transplantation were not significantly different between normal and sham-transplanted rats but were significantly different from rats with ligature of the hepatic artery. These results confirm the validity of the method used for vascular anastomoses. Hypotensive hemorrhage (2 ml/100 g bw) induced marked hemodynamic changes, but rats with liver transplantation when compared with normal and sham-transplanted rats exhibited the following: (a) significantly lower percentage of decrease in cardiac index and in mean arterial pressure; and (b) significantly higher renal and portal tributary blood flows. Plasma catecholamine concentrations and plasma volume were higher in rats with liver transplantation than in normal rats but were not significantly different from sham-operated rats. Histologic examination of the liver revealed slight portal edema in sham-operated rats and small necrotic areas in the liver, probably corresponding to the reperfusion injury, in rats with liver transplantation. In conclusion, the method described for the four vascular anastomoses allows functional perfusion of the transplanted liver. Rats with liver transplantation exhibited a hyperkinetic circulatory syndrome and an improved tolerance to hemorrhage. Changes in plasma catecholamine concentrations and in plasma volume did not account for the hemodynamic changes.

Anastomosis, Surgical↗
PubMed1990

Mesenteric venous stenosis reduces hyperammonemia in the portacaval-shunted rat.

Hyperammonemia is a constant finding following portacaval anastomosis (PCA), and has been incriminated in the neurologic deterioration observed following portasystemic shunt in humans. We developed a rat model for mesenteric venous hypertension by modification of a commonly used technique for studying extrahepatic portal hypertension. We then examined serum ammonia levels in rats undergoing sham operation, mesenteric vein stenosis (MVS) alone, PCA alone, and MVS plus PCA. All MVS animals had a significant (p less than 0.05) elevation in mesenteric venous pressures 2-3 weeks after operation. Serum ammonia levels were normal in rats undergoing sham operation and MVS, and were significantly elevated (p less than 0.001) in rats with PCA. However, a significant (p less than 0.01) reduction in serum ammonia levels was realized when PCA and MVS were combined. These data suggest that intestinal ammonia absorption is a function of splanchnic venous pressure. These findings may be relevant to the management of the neuropsychiatric deterioration seen following PCA in man.

Ammonia↗
PubMed1990

A pitfall in azygos vein cannulation in cirrhotic patients: mistaken cannulation of the mammary vein.

Azygos venous flow can be measured by a thermodilution catheter in patients with cirrhosis. This is a useful technique since azygos flow is thought to reflect the superior portosystemic collateral flow in these patients. The authors report 3 cases in which mistaken internal mammary vein cannulation mimicked azygos vein cannulation in the supine fluoroscopic view. A lateral fluoroscopic view confirmed internal mammary cannulation. They suggest that if the azygos arch is unpronounced or flow measurements are unexpectedly low in patients with portal hypertension due to cirrhosis, a lateral view be performed to rule out internal mammary vein cannulation.

Azygos Vein↗
PubMed1990

Hepatic blood flow in humans during isoflurane-N2O and halothane-N2O anesthesia.

Hepatic blood flow (HBF) (assessed by plasma clearance and hepatic extraction of indocyanine green), cardiac index, and hepatic venous oxygen saturation were measured in patients before and after induction of anesthesia with thiopental, fentanyl, and N2O, and again during halothane (1 MAC)-N2O (n = 5) or isoflurane (1 MAC)-N2O (n = 6) anesthesia before the start of surgery. Induction of anesthesia decreased HBF and cardiac index. Before administration of volatile anesthetics, both groups had similar values of HBF, cardiac index, and hepatic venous oxygen saturation. During anesthesia cardiac index remained stable in both groups, whereas HBF increased significantly with isoflurane but did not change significantly with halothane. Hepatic venous oxygen saturation was also significantly greater during isoflurane than during halothane anesthesia. We conclude that isoflurane increases HBF in anesthetized patients and is associated with a higher hepatic venous oxygen saturation than is halothane.

Adult↗
PubMed1990

Pharmacokinetics of ketanserin in patients with cirrhosis.

The pharmacokinetics of ketanserin, a new serotonin S2 (5HT2) antagonist, were studied in 26 patients with cirrhosis. Patients were randomised to receive either a single oral dose of ketanserin 20mg (n = 14) or 40mg (n = 8) or an intravenous dose of ketanserin 5mg (n = 4). The plasma kinetics of ketanserin and its metabolite ketanserinol were determined over 48 hours, by high pressure liquid chromatography with a fluorometric detector. Pharmacokinetic parameters were calculated using noncompartmental analysis based on a statistical moment theory. The first-pass effect of ketanserin was markedly decreased after oral administration compared with results previously obtained in healthy subjects. The peak concentration was not higher in cirrhotic patients than in controls. This result could be due to an increase in the initial volume of distribution. The production of ketanserinol was reduced in cirrhotics. A decreased mean ketanserin elimination half-life (t1/2 = 12 +/- 4 and 10 +/- 3h vs 16 +/- 3 and 18 +/- 4h in healthy controls after oral ketanserin 40mg and intravenous ketanserin 5mg, respectively) contrasted with a substantial increase in t1/2 for ketanserinol (33 +/- 13 vs 19 +/- 4h). The volumes of distribution were also markedly reduced in patients with cirrhosis. These results suggest either a reduction in the oral dosage of ketanserin or an increase in the interval between doses in patients with cirrhosis.

Administration, Oral↗
PubMed1990

Beta-blockers and portal hypertension, hemodynamic effects and prevention of recurrent gastrointestinal bleeding.

It has been demonstrated that propranolol might reduce portal pressure by reducing cardiac output in patients with cirrhosis and it has thus been hypothesized that beta-blockers may be useful as pharmacological treatment for portal hypertension (1). Subsequently, further studies have detailed the systemic and splanchnic circulatory effects of beta-blockers in patients with portal hypertension and in different models of portal hypertension in animals, and several controlled studies have been performed. This article reviews the hemodynamic effects of beta-blockers in portal hypertension, and reports clinical trials on the prevention of recurrent gastrointestinal bleeding.

Adrenergic beta-Antagonists↗
PubMed1990

Free and conjugated catecholamines in patients with cirrhosis.

A defect of conjugation may play a role in the elevated plasma free norepinephrine observed in patients with cirrhosis. Plasma free, sulfoconjugated, and glucuronoconjugated catecholamine concentrations were assessed in 15 patients with cirrhosis and in 15 age-matched control subjects. Plasma free norepinephrine and epinephrine levels were significantly higher in patients with cirrhosis (481 +/- 75 and 96 +/- 16 pg/ml, respectively) than in those of the control group (307 +/- 33 and 42 +/- 10 pg/ml, p less than 0.05 and p less than 0.01, respectively). Plasma free dopamine levels were similar in both groups. Sulfoconjugated catecholamines were the predominant form in plasma from both cirrhotic patients and control subjects. The ratio of conjugated to total catecholamines was similar in the two groups. Therefore, it is unlikely that a defect in conjugation of catecholamines is contributing to the excessive plasma free norepinephrine and epinephrine concentrations found in patients with cirrhosis. Moreover, in patients with cirrhosis, no significant relation was found between plasma conjugated catecholamines and the severity of liver disease. This study shows that cirrhosis does not induce alteration in conjugation of catecholamines and that hepatocellular function is not essential for conjugation of circulating catecholamines.

Adult↗
PubMed1989

[Effect of hepatic failure upon the pharmacokinetics of cefixime].

Modifications of cefixime kinetics due to severe impairment of liver function were determined in 9 cirrhotic patients. Cefixime was administered as a single dose of 200 mg and levels were measured by HPLC. Maximum serum concentrations and area-under-the-curves of serum concentrations were not modified. The time for maximum serum concentration was delayed and the cefixime half-life in serum was prolonged, as a reflect of increased volume of distribution resulting from ascites and hypoalbuminemia. Renal clearance increased in these patients, possibly because of reduced extra-renal clearance. No metabolite was detected in serum or urine. Modifications of cefixime kinetics resulting from impaired hepatic function were modest and did not require specific dosage adjustment.

Adult↗
PubMed1989

Combination of ketanserin and verapamil or propranolol in patients with alcoholic cirrhosis: search for an additive effect.

Drugs reported to reduce portal pressure through different mechanisms were combined in the hope of either additive portal hypotensive effects in "responders," or inducing a portal hypotensive effect in "nonresponders" to the initial drug. Seven patients with alcoholic cirrhosis received verapamil, 10 mg i.v., and, 60 min later, ketanserin, 5 mg i.v. Verapamil decreased heart rate and increased free hepatic venous pressure but had no effect on hepatic venous pressure gradient or azygos blood flow. When combined with verapamil, ketanserin significantly diminished wedged hepatic venous pressure and hepatic venous pressure gradient. Ten other patients with alcoholic cirrhosis received propranolol, 15 mg i.v., and 45 min later, ketanserin, 5 mg i.v. In all patients, heart rate, cardiac index and azygos blood flow significantly decreased after propranolol. After propranolol alone, however, wedged hepatic venous pressure decreased in only five patients, responders. In five other patients, defined as nonresponders, propranolol did not decrease this pressure. The addition of ketanserin to propranolol induced further significant reduction in wedged hepatic venous pressure, hepatic venous pressure gradient and azygos blood flow. Among the five nonresponders, three had a reduced wedged hepatic venous pressure after ketanserin was combined. We conclude that verapamil does not reduce portal pressure or collateral blood flow in patients with alcoholic cirrhosis. The splanchnic hemodynamic effects of propranolol and ketanserin appear to be independent and additive, without significant systemic alteration.

Drug Synergism↗
PubMed1989

Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in awake portal hypertensive rats.

The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the beta-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 +/- 13 to 293 +/- 10 beats per min (mean +/- S.E.). Cardiac output significantly decreased from 54 +/- 3 to 42 +/- 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 +/- 1 to 18 +/- 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 +/- 17 to 368 +/- 31 dyne per sec per cm5 x 10(3). However, portal pressure showed only an insignificant decrease from 14.9 +/- 1.1 to 14.1 +/- 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 +/- 2 to 66 +/- 4 dyne per sec per cm5 x 10(3), p less than 0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: effects of vasoactive drugs.

To elucidate the relationship between oxygen transport and uptake in cirrhosis, we studied the effects of three vasoactive drugs that change O2 transport. Systemic hemodynamics, blood gases and lactate concentration were measured in patients with alcoholic cirrhosis before and after intravenous dobutamine, propranolol and nitroglycerin. Nine patients received successively dobutamine and then propranolol. Ten patients received nitroglycerin. Three other patients without cirrhosis (controls) received dobutamine. In patients with cirrhosis, dobutamine infusion was accompanied by a significant increase in cardiac output (+21%), systemic O2 transport (+21%) and O2 uptake (+12%), whereas O2 extraction ratio and arterial lactate concentration did not change significantly. Propranolol administration was followed by a significant decrease in cardiac output (-24%) and systemic O2 transport (-25%) and a significant increase in O2 extraction ratio (+19%), whereas O2 uptake and arterial lactate concentration did not change. Nitroglycerin infusion was accompanied by a significant decrease in cardiac output (-21%), systemic O2 transport (-26%) and O2 uptake (-10%), whereas O2 extraction ratio (+18%) and arterial lactate concentration (+31%) significantly increased. In control patients, dobutamine infusion was accompanied by an increase in cardiac output and in systemic O2 transport and by a decrease in O2 extraction ratio, whereas O2 uptake was not modified. These results suggest that O2 uptake may be abnormally dependent on O2 transport in patients with cirrhosis.

Biological Transport↗
PubMed1989

Low dose of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis: evidence for an impaired cardiopulmonary baroreflex function.

High doses of nitroglycerin may decrease portal pressure in patients with cirrhosis with untoward effects such as arterial hypotension and a decrease in systemic O2 uptake. In the present study, low doses of nitroglycerin (7 to 15 micrograms per min, i.v.) were administered in 11 patients with cirrhosis in order to unload cardiopulmonary baroreceptor--one of the possible mechanisms by which nitroglycerin may improve splanchnic hemodynamics--and moreover to avoid deleterious systemic effects. Nitroglycerin significantly decreased right atrial pressure (-35%) and pulmonary wedged pressure (-27%) with significant increase in plasma norepinephrine concentration (+23%), which indicated that cardiopulmonary baroreceptor unloading was achieved. Changes in systemic hemodynamics were slight, although significant, with a decrease in arterial pressure (-8%) and an increase in heart rate (+8%); this indicates a minimal effect on high-pressure baroreflexes. In contrast, no significant change was observed in hepatic venous pressure gradient, hepatic blood flow and azygos blood flow. However, the fraction of cardiac output reaching the azygos system significantly increased by 18%. Plasma renin activity did not change significantly. Moreover, O2 transport and uptake were significantly decreased. These findings show that low doses of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis. These results suggest an impaired cardiopulmonary baroreflex function which is probably located on the efferent arch.

Adult↗
PubMed1989

Hepatic denervation alters hemodynamic response to hemorrhage in conscious rats.

We investigated the effect of liver denervation on cardiovascular homeostasis. Three days after surgical denervation of the liver, hemodynamic studies (radioactive microsphere method) were conducted in conscious rats. The efficacity of the liver denervation procedure was confirmed by a significant decrease in norepinephrine content in various lobes of the liver. Liver denervation did not affect either systemic or splanchnic resting hemodynamics. However, hemorrhage (2 ml per 100 gm body weight) induced a decrease in cardiac index which was significantly more marked in rats with liver denervation (-62 +/- 3%) than in sham-operated rats (-47 +/- 5%; p less than 0.05). This more severe response to hemorrhage may be due to a lack of portal territory vasoconstriction since the fraction of cardiac output reaching portal territory did not decrease during hemorrhage in rats with liver denervation (16 +/- 1% to 14 +/- 1%) but significantly decreased in sham-operated rats (from 15 +/- 1% to 11 +/- 1%, p less than 0.05), this value being significantly lower, after hemorrhage, in sham-operated rats than in denervated rats. The results confirm the lack of tonic neural influence on hepatic circulation during physiological experimental conditions and indicate that hepatic nerve function has a significant contribution to the overall cardiovascular homeostasis.

Animals↗
PubMed1989

Mechanisms of a clonidine-induced decrease in portal pressure in normal and cirrhotic conscious rats.

The effects of clonidine on portal pressure and splanchnic blood flow were studied in conscious rats with sinusoidal portal hypertension due to cirrhosis induced by bile duct ligation. In cirrhotic and sham-operated rats, clonidine (20 micrograms per kg body weight, intravenously) significantly reduced portal, pressure from 19.0 +/- 0.6 to 14.5 +/- 1.0 mmHg and from 9.8 +/- 0.9 to 7.3 +/- 0.5 mmHg, respectively. No significant change in systemic hemodynamics was observed. In cirrhotic rats, clonidine reduced portal pressure, probably by producing a significant increase in portal tributary vascular resistance leading to a 25% decrease in portal tributary blood flow (radioactive microsphere method). In sham-operated rats, clonidine reduced portal pressure presumably by decreasing hepatic portal vascular resistance, since no significant change in portal tributary blood flow was observed. In both groups, clonidine administration significantly decreased plasma noradrenaline concentration. Placebo administration produced neither significant hemodynamic nor significant plasma noradrenaline concentration change. These findings indicate that the sympathetic regulation of the splanchnic circulation is impaired in cirrhotic rats.

Animals↗
PubMed1989

Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations.

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.

Acute Disease↗
PubMed1989

Portal and arterial free and conjugated noradrenaline in two models of portal hypertension in rats.

Free and conjugated noradrenaline concentrations were measured in portal-venous and arterial plasma from sham-operated rats or rats with portal hypertension. Two types of portal hypertension in rats were evaluated: in portal vein stenosed rats, the liver was normal, whereas cirrhosis developed in bile duct ligated rats. In cirrhotic rats, arterial free noradrenaline level was higher than in both sham-operated and portal-stenosed rats, this indicating that enhanced sympathetic nervous activity depends on the development of cirrhosis. In all groups of rats, portal venous plasma free noradrenaline was higher than arterial plasma level, indicating a production of noradrenaline by splanchnic organs. Arterial noradrenaline level may be mainly dependent on this splanchnic production in case of portal hypertension. Sulfoconjugated and glucuronoconjugated noradrenaline plasma levels were similar in the three groups of rats. This shows that alteration in conjugation is not likely to be a major factor in the abnormal circulating levels of free noradrenaline observed in cirrhotic rats.

Animals↗