Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis. Pharmacokinetic-hemodynamic interactions

Isosorbide dinitrate, a long-acting organic nitrate, has been shown to decrease portal pressure in the experimental animal and humans. We conducted a double-blind randomized hemodynamic evaluation of the effects of placebo and 10 mg and 20 mg isosorbide dinitrate in stable individuals with alcoholic cirrhosis. Baseline values for all three groups were similar. Isosorbide dinitrate resulted in a peak reduction of the hepatic venous gradient of 24.7% +/- 3.0%, with significantly decreased values 4 h after the administration of the 20-mg dose. A reduction of arterial pressure and cardiac index (peak decrease of 25.7% +/- 1.5%) was well tolerated by 13 of 15 patients. Changes in mean arterial pressure were not predictive of modifications in the hepatic vein wedge pressure. There was no relation between the area under the plasma isosorbide dinitrate concentration curve and hemodynamic changes. Levels of isosorbide-5-mononitrate, a vasoactive metabolite, were detectable for an 8-h period. Isosorbide dinitrate significantly reduced portal pressure in stable cirrhotics, in association with systemic hemodynamic changes. Thus, titration of isosorbide dinitrate is required to maximize hemodynamic benefits in individual patients. As the decrease in portal pressure is more predictable than the effect of previously tested pharmacologic agents, isosorbide dinitrate should be evaluated for its efficacy in the management of portal hypertension.     

Hemodynamic evaluation of octreotide in patients with hepatitis B-related cirrhosis.

The hemodynamic effects of octreotide were studied in 20 patients with hepatitis B-related cirrhosis. In patients receiving a 100-micrograms bolus and a 100-micrograms/h infusion, heart rate, cardiac index, and systemic vascular resistance showed no significant changes, whereas right atrial pressure, pulmonary capillary wedge pressure, and inferior vena cava pressure decreased significantly after octreotide infusion compared with basal values. In contrast, in patients receiving a 50-micrograms bolus and a 50-micrograms/h infusion, all the systemic hemodynamic values were unaffected. In both groups of patients receiving two different doses of octreotide, the estimated hepatic blood flow, hepatic indocyanine green clearance, and wedge hepatic venous pressure were significantly reduced at 60 minutes after octreotide administration compared with basal values, whereas the hepatic venous pressure gradient remained unchanged. It is concluded that the two different doses of octreotide administration result in the reduction of the wedge hepatic venous pressure and the hepatic blood flow of a similar magnitude, whereas the hepatic venous pressure gradient is unaffected. Octreotide induces discrepant systemic hemodynamic response; this effect is dose related.     

Hemodynamic effects of molsidomine in patients with cardiac insufficiency at high altitudes

Central hemodynamic effects of 0.05 mg/kg molsidomine were examined in 60 patients with decompensated mitral disease dwelling at low and medium altitudes. M-echocardiography was used to assess hemodynamic shifts. The assessments were made during the diagnostic probing of a pulmonary artery in 23 cases. Hemodynamic efficacy of molsidomine was more pronounced up in the mountains. Rationale are given for expanding indications for peripheral vasodilators (molsidomine) in highlanders with congestive heart failure.     

Hemodynamic effects of sublingual molsidomine in patients with or without cardiac failure

A haemodynamic study was performed in 12 men aged between 28 and 64 years, including 8 with clinical signs of congestive cardiac failure and an ejection fraction of less than 50 per cent. The pulmonary artery pressure, capillary pressure, left ventricular pressure, cardiac output and the arterial and venous oxygen tensions were measured before (T 0) and after sublingual administration of 4 mg of molsidomine (T 15, T 30, T 45, T 60 min) and 3 minutes after a dose of 0.6 mg sublingual trinitrine (given immediately after the measurements made at T 60). The haemodynamic modifications were very significant at the 30th minute and reached a plateau between the 45th and 60th minute. The left and right ventricular filling pressures fell by more than 25 per cent, the aortic pressure fell by 17 per cent. There was a mild decrease (8 per cent) in the cardiac index and the systolic index, without any significant change in the heart rate. The reduction in the cardiac index and the systolic index was not significant in patients with cardiac failure and an ejection fraction of less than 50 per cent. The peripheral vascular resistance fell by 9 per cent. Finally, there was a significant reduction in the cardiac work and power and especially in the pressure-time index per beat and per minute. The administration of 0.6 mg of sublingual trinitrine induced an additional reduction in the aortic pressure with acceleration of the heart rate and a slight increase in the cardiac output, but no additional venodilator effect was detected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic properties of bucindolol, a beta-adrenoreceptor blocking drug with vasodilator activity

Bucindolol is a new nonselective beta-adrenergic blocking agent with direct vasodilator, partial agonist and alpha-adrenergic blocking properties. Its hemodynamic effects were evaluated in 13 healthy young men. In an open study, the effects of increasing single oral doses (50 to 200 mg) were examined. Two hours after each dose there was little effect at rest, but the responses of heart rate and systolic blood pressure to cycle exercise (50 to 150 W) were significantly reduced. There was no greater effect with larger doses. The second phase was a 3-way double-blind study comparing the effects of placebo with 50 and 200 mg of bucindolol. Left ventricular (LV) ejection phase indexes derived from digitized M-mode echocardiograms (% fractional shortening, mean and peak velocity of circumferential fiber shortening, stroke volume) increased more than 10% 2 and 4 hours after bucindolol was administered, whereas systemic vascular resistance and the ratio preejection period/LV ejection time decreased to the same extent. Although there was little effect on measurements at rest, the response to cycle exercise of heart rate and systolic blood pressure were significantly attenuated. These results show that the effects of bucindolol on LV systolic function are related at least in part to reduction of afterload, but do not indicate whether the drug has an additional direct inotropic effect.     

酒精性肝硬化患者临床特征分析

目的 总结酒精性肝硬化患者的临床特征.方法 2016年6月～2019年6月我院收治的87例酒精性肝硬化患者和96例乙型肝炎肝硬化患者,接受超声检查,收集临床资料,计算中性粒细胞/淋巴细胞计数比值(NLR),比较两种肝硬化患者临床特点的异同.结果 酒精性肝硬化患者男性占比为86.2％,显著高于乙型肝炎肝硬化(70.8％,...     

Zinc absorption in patients with compensated alcoholic cirrhosis

Zinc absorption was measured by whole-body counting in 10 patients with compensated alcoholic cirrhosis without steatorrhoea and in 8 healthy subjects. After oral administration of 65Zn the absorption was measured at regular intervals until a straight time/activity retention curve was obtained in a semilogarithmic system, whereafter it was calculated by extrapolation to time zero. Cirrhotic patients had a median absorption of 69% (27-90%), compared with 42% (25-67%) in healthy subjects (P less than 0.01). Median T1/2 of 65Zn as calculated from the retention curve was 156 days (83-280 days) in cirrhotic patients and 103 days (72-132 days) in healthy subjects (P less than 0.05). Median serum zinc value was 11 mumol/l (9-17 mumol/l) in cirrhotic patients and 16 mumol/l (12-17 mumol/l) in healthy subjects (P less than 0.01). Median erythrocyte zinc value was 224 mumol/l (205-281 mumol/l) in cirrhotics and 223 mumol/l (188-275 mumol/l) in healthy subjects (P less than 0.1). Six cirrhotic patients, of whom four took diuretics, had increased urinary zinc excretion (greater than 15 mumol/24 h). Zinc absorption seems intact in compensated alcoholic cirrhosis. The increased absorption and prolonged T1/2 of 65Zn might be compensatory to a moderate zinc depletion.     

Abstinence in patients with alcoholic liver cirrhosis: A follow-up study

Aim:  To investigate the proportion of patients with alcoholic cirrhosis who abstained from alcohol after contact with a hepatology unit, the predictors for abstinence, and the role of clinical and psychosocial factors in short-term mortality in these patients.
Methods:  Eighty-seven consecutive patients with alcoholic cirrhosis from a transplant center were included. Data on cirrhosis severity and complications, as well as on abstinence and psychosocial factors were collected. Patients were followed up for 19 (12–25) months. Data on abstinence during follow up, alcohol abuse treatment, psychiatric contact, severity of cirrhosis, mortality, and liver transplantation were analyzed.
Results:  Prior to inclusion, 53/87 (61%) patients had abstained from alcohol for 24 months (interquartile range: 18–33). Twenty percent had a history of other substance abuse, 47% had undergone alcohol abuse treatment, and 21% had a previous psychiatric diagnosis. Forty-eight percent lived with a partner, 23% worked/studied, and 53% were pensioners. During follow up, 26% died, 20% received a liver transplant, 55% abstained from alcohol, 47% received alcohol abuse treatment, and 33% had psychiatric contact. In a multivariate analysis, abstinence during follow up was found to be related to abstinence upon inclusion in the study, to the model for end-stage liver disease (MELD) score at follow up, and to no abuse treatment in a detoxification unit, whereas mortality was related to index MELD and alcohol abuse treatment during follow up. Neither abstinence nor mortality was related to psychosocial factors.
Conclusion:  More than half of patients with alcoholic cirrhosis were found to abstain from alcohol during follow up, which was related to prior documentation of abstinence and cirrhosis severity. Cirrhosis severity (expressed as the MELD) and alcohol abuse treatment during follow up were related to short-term mortality.     

酒精性肝硬化患者的临床特征

目的 探讨单独酒精或酒精合并病毒感染所致肝硬化临床表现的异同.方法 收集2004-2008年在中国医科大学附属第一医院住院的明确诊断为肝硬化的329例病例资料,其中单独酒精所致肝硬化(alcoholic liver cirrhosis,ALC)104例(28.18%)、单独乙型肝炎所致肝硬化(chronic HBV-r...     

Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis

A decrease in plasma noradrenaline--a reflection of sympathetic nervous system activity--by clonidine, a centrally acting alpha 2-agonist, could reduce the hyperdynamic circulation observed in cirrhosis and may thereby decrease portal hypertension. Plasma noradrenaline concentration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after administration of either 150 micrograms of clonidine or placebo. Plasma noradrenaline concentration significantly decreased in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (-17.4%), mean arterial pressure (-12.2%), hepatic venous pressure gradient (-19.7%) and azygos blood flow (-26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and changes in systemic or splanchnic hemodynamics. Hepatic blood flow was not changed by clonidine. Placebo administration had no effect on any laboratory or hemodynamic measurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation suggests that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.     

Small bowel bacterial overgrowth in patients with alcoholic cirrhosis

A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid.     

Small bowel bacterial overgrowth in patients with alcoholic cirrhosis

A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid.This study was supported in part by a grant (No. 91/0675) from Fondo de Investigaciones Sanitarias (FIS), Madrid, Spain.This article originally appeared inDigestive Diseases and Sciences, Volume 40, Number 6, June 1995, pp. 1252–1256.     

Thyroid status in fifty patients with alcoholic cirrhosis.

Because the liver is of considerable importance in metabolism of thyroid hormones, plasma levels of thyroxine (T4), triiodotyronine (T3) with their unbound fractions (FT4 and FT3), reverse T3 (rT3)--an inactive isomer of T3-tyrotropin (TSH) and TSH response to thyrotropin releasing hormone (TRH; 250 micrograms i.V.) were determined by radioimmunoassays in 50 clinically euthyroid patients with alcoholic cirrhosis. T4 mean concentration (7.3 micrograms/dl) did not differ from normal values but T3 was decreased (101 vs 154 ng/dl; p less than 0.001) and was correlated with the degree of liver damage appreciated by a clinico-biological index. FT4 was elevated in patients (17.1 vs 13.1 pg/ml; p less than 0.02) although FT3 was slightly decreased (3.4 vs 4.5 pg/ml; p less than 0.10) with an increased FT4: FT3 ratio (7.0 vs 3.0; p less than 0.02). rT3 was elevated (592 vs 206 ng/100 ml; p less than 0.001) and correlated with FT4/FT3: rT3/T3 ratio (p less than 0.01) and with the severity of the cirrhosis. Basal TSH levels (3.3 microU/ml) and TSH responsiveness to TRH was normal though very scattered, and independant from T3 and T4 values. It may be concluded that: 1. euthyroidy in cirrhosis assessed by a normal responsiveness to TRH, results from a compensatory increase in FT4. 2. The low T3 and FT3 levels may proceed from an impairment of peripheral T4 in to T3 conversion with a deviation pathway towards rT3. 3. T3 and rT3 levels provide valuable index of the severity of the cirrhosis.