The effect of propranolol on thyroid function in patients with liver cirrhosis

The effect of propranolol on thyroid hormones of 7 healthy subjects and 10 patients with histologically proven alcoholic liver cirrhosis was investigated. The fractions of plasma T3 and free T4 were determined by specific radioimmunoassay before and after two weeks of propranolol administration. Under basal conditions, both T3 and FT4 levels were found significantly lower in patients with cirrhosis than in healthy subjects (1.86 +/- 0.10 vs. 1.18 +/- 0.41 nmol/l, p less than 0.001; 9.31 +/- 0.41 vs. 8.17 +/- 0.91 pg/ml, p less than 0.05, respectively). In healthy subjects propranolol administration led to a significant reduction of T3 serum levels (from 1.88 +/- 0.10 to 1.51 +/- 0.12 nmol/L, p less than 0.001), while in patients with liver cirrhosis no significant changes in T3 and FT4 were found. In patients with liver cirrhosis propranolol administration did not affect thyroid hormone levels.     

Relationship among gastric motility, autonomic activity, and portal hemodynamics in patients with liver cirrhosis

BACKGROUND AND AIMS: We examined the effects of the autonomic nervous function and the volume of portal blood flow to clarify the mechanism of the abnormal gastric motility in patients with liver cirrhosis. METHODS: Heart rate variability, electrogastrogram (EGG), and volume of portal blood flow were measured before and after a meal in 27 patients with liver cirrhosis (LC group) and in 20 normal subjects (N group). Autonomic nervous function was evaluated by using spectral analysis of heart rate variability. We used the cine phase-contrast (PC) method, using magnetic resonance imaging (MRI) to measure the portal flow, while the peak frequency and spectral power of the EGG were measured at pre- and postprandial change. RESULTS: The ratio of low frequency power to high frequency power (LF/HF) was significantly higher, and the HF power was significantly lower in the LC group than in the N group both before and after a meal. In both groups, the electrogastrographic peak power ratio before and after a meal showed a positive correlation with the HF ratio, and an inverse correlation with the LF/HF ratio. In addition, portal blood flow volume was significantly decreased in the LC group than in the N group. However, the increased rate of portal blood flow after a meal correlated positively with the increased rate of electrogastrographic peak power. Moreover, gastric motility was positively correlated with esophageal varices and coma scale with the use of multivariate analysis. CONCLUSIONS: Parasympathetic hypofunction, sympathetic hyperfunction and portal hemodynamics were closely related with gastric motility in cirrhotic patients. In addition, gastric motility was decreased, at least in part, by the ingestion of food in cirrhotic patients because of abnormalities in autonomic functions and portal blood flow following a meal.     

幽门螺杆菌感染对肝硬化患者血氨浓度的影响

探讨肝硬化患者幽门螺杆菌(Hp)感染与血氨的关系,及根除性治疗Hp对血氨的影响。84例肝硬化高血氨患者,分为Hp阳性组51例,阴性组33例。两组都给予支链氨基酸、乳果糖、基础护肝治疗两周,治疗前后分别测空腹静脉血氨。随后将Hp阳性组随机分两组,A组26例,应用三联疗法治疗一周;B组25例,奥美拉唑治疗一周,治疗结束一个月后复查血氨。发现阳性组的血氨与阴性组相比有显著差异(P＜0．01)。阳性组不同肝功能分级组血氨浓度之间有显著差异(P＜0．01);阴性组则否。Hp阴性组治疗前后血氨浓度变化差异有显著性(P＜0．01),阳性组则无显著差异。根除Hp治疗后血氨明显下降(P＜0．01),而用洛赛克治疗后血氨轻度升高,但无统计学意义。说明Hp感染与肝硬化患者血氨升高有密切相关性,根除Hp的治疗能有效降低血氨。     

肝硬化患者体表胃电图参数与肝功能损害程度的相关性研究

探讨肝硬化患者体表胃电图参数变化与肝功能及检验指标间的关系。对63例肝硬化患者和20例健康志愿者进行体表胃电图记录和化验检查。将健康对照组、Child-pugh分级A级、B级、C级四级受试者进行两两比较,主频和胃电节律紊乱百分比均有显著差异;胃电节律紊乱百分比与肝功能检验指标进行相关性分析,发现白蛋白和血小板计数与胃电节律紊乱百分比存在直线负相关关系(r分别为-0.723和-0.704)。1.肝硬化患者存在明显胃电节律紊乱,并随肝功能损害程度加重而加重;2.白蛋白和血小板计数与肝硬化患者胃电节律紊乱关系密切,可用于判断肝硬化患者胃动力障碍情况。     

血清胆碱酯酶与肝硬化Child-Pugh分级及血清肝纤维化指标的相关性

目的 探讨肝硬化患者血清胆碱酯酶与肝硬化病变程度及血清肝纤维化指标的关系。方法 测定肝硬化患者血清胆碱酯酶及血清肝纤维化指标。结果 随着临床肝硬化程度的加重，血清肝纤维化指标逐渐增高，胆碱酯酶则逐渐降低。肝硬化患者CHE与PCⅢ、IC-C、LN及HA呈负相关（P〈0．001），CHE与LN之间的相关性随着肝硬化病情加重而更加明显（P〈0．001）。结论 肝硬化时血清胆碱酯酶与肝纤维化有一定相关性。联合检测PCⅢ、Ⅳ-C、LN、HA及胆碱酯酶对估测肝硬化的严重程度及预后估计有一定的临床价值。     

肝硬化患者心功能改变及其与肝功能的关系

目的研究肝硬化患者的心脏结构和功能变化,探讨其与肝功能的关系。方法 35例肝硬化患者按照肝功能Child-Pugh分级,A级12例（A组）,B级13例（B组）,C级10例（C组）。20例健康体检者为对照组。利用超声心动图测量静息状态下左室射血分数（EF）、左室直径（Vd）、左房直径（LAs）、右室直径（RVd）、E/A比值、室间隔厚度（IVS）、左室后壁厚度（LVPW）、主动脉瓣环直径（AAO）等指标。结果肝硬化组LAs大于对照组（P=0.000）,A组与B组间比较差异无统计学意义（P=0.248）,A组与C组比较,A组LAs小于C组（P=0.039）,B组与C组比较,B组LAs小于C组（P=0.008）。肝硬化组AAO大于对照组（P=0.000）;IVS肝硬化组大于对照组（P=0.026）;E/A值肝硬化组小于对照组（P=0.002）。结论肝硬化患者存在左心功能不全,以舒张功能不全为主,并与肝功能具有一定关系,提示肝硬化心肌病的存在。当肝硬化患者行心脏二维多普勒超声出现LAs增大、E/A〈1时需注意肝硬化心肌病的可能。     

Regional hemodynamic effects of beta-adrenergic blockade with propranolol in the unanesthetized primate

The effects of equal doses of d- and dl-propranolol on systemic and regional hemodynamics were studied in the unanesthetized rhesus monkey using the radioactive microsphere technique. No changes in systemic hemodynamics were seen with d-propranolol, but dl-propranolol significantly decreased the cardiac output (?25 per cent), heart rate (?18 per cent), and stroke volume (?9 per cent), and increased the total peripheral resistance (+40 per cent). During the dl-propranolol infusion the cardiac output was preferentially distributed to the brain with a small decrease in the fraction received by the liver. Flow to all organs except the brain was diminished during dl-propranolol, and the decrease was proportionate to the change in cardiac output. No change in distribution of flow was seen with d-propranolol and total flow to all organs was unchanged from control, with the exception of an increase in flow to the skin. This comparison of d- and dl-propranolol indicates that the effects of dl-propranolol are due to beta-adrenergic blockade rather than a non-specific effect of the drug.     

Splenectomy improves liver function in patients with liver cirrhosis

BACKGROUND/AIMS: Partial splenic embolization or splenectomy has been reported to improve liver function as well as hypersplenism. The aim of this study was to evaluate the effects of splenectomy in patients with liver cirrhosis (LC) on liver function. METHODOLOGY: Twelve consecutive patients with LC were followed for more than 6 months using laboratory examinations, ultrasonography (US) and computed tomography. Portal blood flow was measured using color Doppler US before and after splenectomy in 6 cases. RESULTS: Hypersplenism was improved in all patients. Protein synthesis in the liver was improved, which significantly correlated with these patients' increased liver volume. Having a large spleen and a low serum alanine aminotransferase (ALT) levels are predictive factors for favorable improvement of liver function after splenectomy. Splenectomy was safely carried out in all patients without major complications except for portal thrombus occurred in 4 patients, but did not affect liver function if it was well treated. CONCLUSIONS: Splenectomy improved liver function in patients with LC, and could be a supportive and bridging therapy for patients waiting for liver transplantation, especially with large spleen and lower ALT levels.     

肝硬化患者血清瘦素水平变化及相关因素分析

目的 探讨瘦素在肝硬化发生、发展中的作用.方法 对44例肝硬化患者(肝硬化组)和17例健康查体者(正常对照组)进行血清瘦素、空腹血糖(FPG)、胰岛素(FINS)水平测定并分析相关因素.结果 肝硬化组血清瘦素水平显著高于对照组(P<0.01),肝功能Child-pugh B、C级者显著多于A级(P<0.05);血清瘦素水平与FINS、FPG、胰岛素敏感指数(ISI)呈显著正相关,FINS是瘦素的显著预测因子.结论 肝硬化患者瘦素水平显著升高;其可能通过胰岛素抵抗诱发肝性糖尿病.     

Hemodynamic and beta-adrenergic receptor adaptations during long-term beta-adrenoceptor blockade. Studies with acebutolol, atenolol, pindolol, and propranolol in hypertensive patients

In an attempt to further clarify the mechanism of the maintenance of the antihypertensive effect of beta-adrenoceptor antagonists, the effects of four antagonists with different ancillary properties (acebutolol, atenolol, pindolol, and propranolol) on systemic and renal hemodynamics, body fluid volumes, hormones, and lymphocyte beta-adrenoceptor density were studied in four groups of 10 hypertensive patients. The patients were observed for 3 weeks during active treatment and for 2 weeks after withdrawal of treatment. At the end of the 3-week treatment period, the four drugs had an equal antihypertensive effect (fall in mean arterial pressure, 10-13%). Although renin activity was suppressed (60-70%) by all four drugs, changes in renin or pretreatment values of renin levels were not correlated with the fall in blood pressure. The drugs had no effect on plasma catecholamine concentrations or body fluid volumes. Despite similar antihypertensive effects among the four drugs, the changes in flow and resistance underlying the fall in blood pressure differed considerably. With pindolol, the fall in blood pressure was associated with a fall in vascular resistance (26 +/- 6%), whereas with propranolol, it was predominantly associated with a fall in cardiac output (11 +/- 7%). No significant changes in vascular resistance or cardiac output occurred with atenolol or acebutolol. The changes in renal blood flow and renal vascular resistance occurred in parallel with the changes in cardiac output and systemic vascular resistance. Plasma epinephrine concentration and pretreatment cardiac chronotropic responsiveness to isoproterenol appeared to be inversely correlated with lymphocyte beta-adrenoceptor density (Bmax) (r = -0.41 and -0.43, respectively). With pindolol, Bmax decreased maximally by 39 +/- 6%, and with propranolol, it increased by 51 +/- 17%. With both drugs, significant changes in Bmax were already present 24 hours after treatment. Furthermore, 1 week after withdrawal of treatment with pindolol, Bmax was still down-regulated, and cardiac chronotropic responsiveness was still decreased, whereas 1 week after withdrawal of propranolol, Bmax was still up-regulated, and cardiac chronotropic responsiveness was still increased. No changes in Bmax occurred with the beta 1-selective antagonists acebutolol and atenolol. Thus, despite an equal antihypertensive effect, the four beta-adrenoceptor antagonists appear to have dissimilar effects on cardiac output, renal blood flow, and lymphocyte beta-adrenoceptors. Changes in cardiac output, the circulating blood volume, or angiotensin-mediated vasoconstriction are factors unlikely to be crucial for the antihypertensive effect of beta-adrenoceptor antagonists. Therefore, interference with vasoconstrictor nerve activity through blockade of either central or peripheral prejunctional beta-adrenoceptors could be an alternative explanation of their blood pressure-lowering potential.     

Effects of 5-isosorbide mononitrate and propranolol on subclinical hepatic encephalopathy and renal function in patients with liver cirrhosis

BACKGROUND/AIMS: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study. METHODOLOGY: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured. RESULTS: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables. CONCLUSIONS: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.     

Hemodynamic effects of beta-adrenergic blockade with pindolol, oxprenolol, propranolol and bufetolol hydrochloride in essential hypertension.

Hemodynamic studies (using (131)I-labeled albumin [RISA]) Were performed before and 5 and 42 weeks after the oral administration of pindolol (av. 30 mg/day), oxprenolol (av. 216 mg/day), propranolol (av. 75 mg/day) or bufetolol hydrochloride (av. 30 mg/day) in 40 patients with essential hypertension. Responders to the antihypertensive actions of short-term (5 weeks) pindolol or bufetolol showed a reduction in total peripheral resistance (pindolol, from av. 2622 to 2022 dyne-sec-cm-5-m2; befetolol, from av. 3301 to 2620, p less than 0.05), without significant changes in cardiac index, while hypotensive actions of propranolol or oxprenolol appeared to be due mainly to a decrease in cardiac output (propranolol, from av. 4.03 to 2.99 L/min/m2; oxprenolol, from av. 3.97 to 3.29 L/min/m2), although the decrease in cardiac output was not significant. In long-term (42 weeks) oxprenolol therapy, antihypertensive effects seemed to be related to reduced cardiac output and a readaptation of peripheral resistance to chronic reduction of cardiac output was not always observed. Circulation time was determined in 9 patients with oxprenolol therapy and 8 with pindolol therapy by the measurement of the arrival time in the cerebral hemisphere of the intravenously injected radioisotope. The patients with oxprenolol therapy showed significant prolongation in circulation time (short-term administration, av. 6.6 to 8.4 sec; long-term administration av. 6.6 to 9.2 sec, p less than 0.05), while no prolongation was observed in pindolol therapy. These results suggest that hemodynamic responses to beta-blocking agents are not uniform and that the antihypertensive actions of beta-blockers depend on the effects on both cardiac output and peripheral vascular resistance.     

Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis

Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta-adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.     

Acute non-selective beta-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis

BACKGROUND/AIMS: Earlier studies have shown a prolonged frequency-adjusted Q-T interval (QTc>0.440 s(1/2)) in a substantial fraction of patients with cirrhosis. The effect of beta-blockade on QTc is unknown, and its determination was the aim of the study. METHODS: Seventeen patients with cirrhosis received 80 mg propranolol orally during a haemodynamic investigation with measurements at baseline and 90 min after propranolol ingestion. RESULTS: Beta-blockade reduced cardiac output (-21%, P<0.001), heart rate (-20%, P<0.001), and the hepatic venous pressure gradient (HVPG, -17%, P<0.02). The mean QTc=0.460 s(1/2) was prolonged compared to 0.410 s(1/2) in age-matched controls (P<0.01). Whereas QTc decreased during beta-blockade in the cirrhotic patients (from 0.460 to 0.440 s(1/2), P<0.01), no effect was found in the subgroup with normal QTc (0.429 vs. 0.422 s(1/2), ns), and a reduction was seen in the patients with prolonged QTc (from 0.488 to 0.456 s(1/2), P<0.01). The percentage decrease in QTc was related to the reduction in HVPG (r=0.48, P=0.03) and cardiac output (r=0.56, P=0.02). CONCLUSIONS: Acute non-selective beta-blockade reduces prolonged QTc towards normal values in patients with cirrhosis. The clinical significance of QTc reduction in arrhythmia is a topic for future research.     

肝硬化与肺功能异常的关系

目的:了解肝硬化患者肺功能异常与肝病之间的关系.方法:选取2007-05/2008-03我院及中山大学附属第一医院住院肝硬化患者50例.肺功能检测患者第一秒用力呼气量(FEV1)、一秒率(FEV1/FVC),单次呼吸法检测肺一氧化碳弥散量(DLCO)、比弥散量(KCO,即单位肺泡的DLCO).将肝硬化患者分别按患者肝掌、蜘蛛痣、显性黄疸、白蛋白减低、脾亢、门静脉增宽等的异常与否分成阳性组(+)和阴性组(-),比较组间FEV1、FEV1/FVC、DLCO、KCO均值的差异.结果:约34%患者出现通气功能障碍,以限制性通气为主:有72%的患者出现弥散功能减退,为最主要的肺功能改变.Child-Pugh积分与KCO呈负相关(r=-0.351,P<0.05);白蛋白水平与FEV1、KCO呈正相关(r=0.334,0.336,均P<0.05);门静脉宽度与FEV1、DLCO呈负相关(r=-0.389,-0.417,均P<0.05);脾厚度与DLCO、KCO呈负相关(r=-0.644,-0.536,均P<0.01).血红蛋白浓度和脾脏厚度是DLCO的独立预测因子(P<0.05).结论:弥散障碍在肝硬化患者中发生率较高,门静脉高压的长期作用与之有密切关系.     

Effects of propranolol on renal blood flow and renal function in patients with cirrhosis

Systemic and splanchnic hemodynamics, renal blood flow, and renal function were studied in 13 patients with cirrhosis both before and 1 h after oral administration of 40 mg of propranolol (acute administration) and 1 mo after continuous administration of this substance at doses reducing the heart rate by 25% (chronic administration). Cardiac output and the gradient between wedged and free hepatic venous pressures significantly decreased after acute and chronic administration of propranolol; mean arterial pressure did not change significantly and systemic vascular resistance significantly increased. Renal blood flow and renal vascular resistance did not change significantly after acute administration of propranolol and renal function did not change significantly after acute or chronic administration of propranolol. We conclude that propranolol does not alter renal function in patients with cirrhosis who are in good physical condition.     

Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis

The effects of beta-blockade with propranolol and of alpha-adrenergic stimulation with methoxamine, a powerful alpha-agonist, on azygos blood flow and on systemic and hepatic haemodynamics were investigated in 26 cirrhotic patients with portal hypertension. Beta-adrenergic blockade with propranolol (n = 12), evidenced by a significant reduction of heart rate (-17 +/- 1%, P less than 0.001) and cardiac index (-17 +/- 2%, P less than 0.001), caused a mild but significant decrease of hepatic venous pressure gradient (-10 +/- 2%, P less than 0.05) and a marked fall of azygos venous blood flow (-31 +/- 5%, P less than 0.05). Alpha-adrenergic stimulation with methoxamine (n = 14), manifested by a significant increase of mean arterial pressure (19 +/- 2%, P less than 0.001), mimicked the effects of propranolol on hepatic venous pressure gradient (-10 +/- 4%, P less than 0.05) and cardiac index (-11 +/- 2%, P less than 0.001). However, azygos blood flow was not significantly reduced by methoxamine (0.7 +/- 0.1 vs 0.6 +/- 0.1 l/min). On the contrary, hepatic blood flow was significantly reduced by methoxamine (-19 +/- 4%, P less than 0.01) but not by propranolol (-7 +/- 7%, ns). Similarly, in 8 patients who received methoxamine after being beta-blocked by propranolol, azygos blood flow, that was markedly reduced by beta-blockade, did not experience a further reduction but increased slightly by alpha-adrenergic stimulation, while hepatic blood flow, that was not reduced by propranolol, decreased significantly during the subsequent methoxamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)