Influence of propranolol and pindolol on the haemodynamic effects of papaverine,isoprenaline and noradrenaline in hypertensive patients

Summary The influence of two -adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p<0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p<0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the -blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both -blockers. While the -blockers inhibited the -adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the -adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the -and -adrenoceptor effects of noradrenaline.Abbreviations BP blood pressure - ECG electrocardiogram - HR heart rate - ISA intrinsic sympathomimetic activity     

Acute and long-term haemodynamic effects of propranolol and indenolol in hypertension

Summary The haemodynamic effect of indenolol, a -adrenoceptor blocker with intrinsic sympathomimetic activity (ISA) in animals, has been evaluated in a double-blind cross-over randomized trial after acute (3 days) and long-term treatment (28 days), in 12 hypertensive patients in comparison with that of propranolol. Patients were evaluated at rest and during isometric exercise (hand grip). The overall acute effect of both -adrenoceptor blocking drugs was to decrease mean blood pressure, heart rate and cardiac output, while total peripheral resistance increased. In the long-term studies the haemodynamic effect of propranolol was still characterized by cardiodepression and unchanged peripheral resistance. Patients on the long-term treatment with indenolol showed normal cardiac output and reduced total peripheral resistance.The data are compatible with a relatively strong ISA of indenolol, which would be responsible for the haemodynamic pattern observed during chronic treatment.     

Comparison of the acute haemodynamic effects of bopindolol and propranolol at rest and during supine exercise

Summary The acute cardiovascular effects of two beta-adrenoceptor blocking agents, bopindolol and propranolol, were compared in a randomized study in 16 male patients with coronary heart disease. All patients had had an uncomplicated acute myocardial infarction at least 8 weeks earlier.The two drugs reduced the arterial blood pressure to the same extent, both at rest and during exercise. As heart rate and stroke volume were also decreased, cardiac output was reduced, whereas systemic vascular resistance was increased at rest and during exercise. Left ventricular filling pressure was increased.No statistically significant differences in these variables were seen between the two groups.     

Beta-adrenergic blocking activity and haemodynamic effects in man of Kö 1313, a new beta-adrenergic antagonist

Summary The beta-adrenergic blocking activity and haemodynamic effects of o-[2-hydroxy-3-(isopropylamino)-propoxy]-benzonitril (Kö 1313) have been studied in 22 patients. Antagonism of isoproterenol-induced tachycardia was used as a measure of the beta-adrenergic blocking activity. Kö 1313 1.0 mg had its maximum beta-adrenoceptor blocking effect 5–30 min after intravenous injection. Kö 1313 10.0 mg produced maximum betablockade 1–4 h after oral administration. 1.0 mg Kö 1313 injected intravenously had approximately the same beta-adrenergic blocking effect as 1.0 mg propranolol also given intravenously. After intravenous administration Kö 1313 was 3–4 times as potent as the same dose given orally. An intravenous dose of 2.0 mg Kö 1313 reduced the heart rate and produced insignificant fall in cardiac output. Total peripheral resistance was increased by Kö 1313.A preliminary account of this work has already been published (H. J. Gilfrich und K. H. Rahn, Verhandlungen der Deutschen Gesellschaft für Innere Medizin76, 925 (1970)).     

Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease

Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16).The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 g·h·l^–1, 923 g·h·l^–1 and 1300 g·h·l^–1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively.Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h^–1 in patients vs. 2.00 h^–1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls.Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.     

普萘洛尔预防肝硬化上消化道再出血的荟萃分析

目的 :对普萘洛尔能否预防肝硬化并发上消化道出血进行系统评价。方法 :检索 1 980年 1月至 2 0 0 0年 1 2月期间发表的有关普萘洛尔预防肝硬化并发上消化道出血的随机对照临床试验。按照入选标准 ,有 9项临床试验纳入本研究。结果 :上消化道再出血和因出血死亡的合并优势比 (OR)分别为0 .3 0 [95 %CI 0 .2 2 ,0 .42 ],0 .43 [95 %CI 0 .2 3 ,0 .84],P <0 .0 5 ;而死亡的OR为 0 .67[95 %CI0 .44,1 .0 4],P >0 .0 5。肝功能越差 ,预防效果越好。结论 :普萘洛尔可以预防肝硬化并发上消化道再出血 ,并可降低再出血所致的死亡率。肝功能的状况是影响普萘洛尔的预防效果的重要因素     

The central haemodynamic effects of a single intravenous dose of flosequinan in patients with severe heart failure

Summary The acute central haemodynamic and neuroendocrine effects of intravenous flosequinan were studied in a group of 10 patients with severe heart failure.Flosequinan improved cardiac output by a maximum of 1.59 l·min^–1, it reduced pulmonary capillary wedge pressure by 11.9 mm Hg and it also caused a reduction in right atrial pressure by a maximum of 7.2 mm Hg. It tended to cause a fall in plasma adrenaline levels but not in plasma noradrenaline. There was little fall in blood pressure in response to flosequinan and no patient developed an adverse event.Intravenous flosequinan may be a useful candidate drug for controlled clinical studies in patients with severe heart failure.     

肝硬化患者幽门螺杆菌感染与血清肌钙蛋白T的关系

目的：探讨肝硬化患者幽门螺杆菌（HP）感染与血清肌钙蛋白T（cTNT）的关系。方法：乙肝后硬化患者140例,经检测HP后分HP阴性和阳性组,并设正常对照组,分别测定各组的cTNT;对于HP阳性病例根治HP后再次测定cTNT,并与根治前进行比较;同时,将HP阳性病例分为大量感染组、中量感染组及少量感染组,分别比较各组的cTNT;另外,对于HP阴性和阳性组病例,根据肝功能Child分级进行分组,分别比较各组的cTNT。结果：HP阳性组cTNT明显高于HP阴性组和对照组（P＜0．01）,HP阴性组明显高于对照组（P＜0．05）,HP根治后cTNT显著下降（P＜0．01）;大量感染组明显高于中量及少量感染组（P＜0．01－0．05）;中量感染组亦明显高于少量感染组（P＜0．01）;HP阳性组中肝功能Child C、B级组明显高于A级组（P＜0．01）C级组又明显高于B级组（P＜0．05）,而HP阴性组中各组之间差异无显著意义（P＞0．05）。结论：HP感染使肝硬化患者血cTNT升高,易于并发心肌损害,根治HP有利于防治该并发症。     

肝硬化患者肝血流改变与组织羟脯氨酸的关系

目的　观察彩色多普勒 (CDFI)超声检测肝门静脉 (PV)的意义。方法　运用CDFI超声检查了75例肝硬化患者的PV ,并按Puph肝功能分级法进行统计学处理 ,与正常组 30例进行对比分析。 结果　脉冲多普勒 (PW )可显示血流速度正常 ,减低或双向血流 ;血流速度、血流量随着Puph肝功能分级程度严重而下降 ;与正常组比较差异有显著意义 (P <0 0 5 ) ;肝硬化患者组织羟脯氨酸 (Hyp)、丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、白蛋白 (ALB)和透明质酸 (HA)水平均高于正常对照组 (P <0 0 5～ 0 0 1) ,并随着肝硬化严重程度其水平不断上升 (P <0 0 5～ 0 0 1) ;肝组织Hyp的含量与肝纤维化程度呈正相关 (r =0 5 6 12 ,P <0 0 5 )。结论　CDFI检测门静脉不仅能诊断肝硬化 ,而且能判断肝硬化损害的程度     

Elimination and haemodynamic effects of nitrendipine in patients with chronic renal failure

Summary In sixteen patients with arterial hypertension and differing degrees of renal function the pharmacokinetics and haemodynamic effects of nitrendipine have been studied after treatment for 7 days. The AUC (0–24) and the elimination half-life of nitrendipine were significantly increased; the AUC (0–24) in patients with renal failure (median creatinine clearance 27.1 ml × min^–1) was 196 ng × ml^–1 × h compared to 97.8 ng × ml^–1 × h in control subjects (median creatinine clearance 94.4 ml × min^–1). The corresponding elimination half-lives were 13.5 h in renal failure and 4.4 h in the controls. The haemodynamic effects of nitrendipine were not enhanced in the patients.     

Reduced peripheral vascular symptoms in elderly patients treated with α-methyldopa — A comparison with propranolol

Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.     

Effects of acute and long-term beta-adrenoceptor blockade with propranolol on haemodynamics,plasma catecholamines and renin in essential hypertension

Summary The effect of an acute intravenous and repeated oral doses of propranolol on haemodynamics, plasma and urinary catecholamines and plasma renin activity was studied in patients with essential hypertension. Intravenous injection of propranolol 5 mg produced a fall in cardiac output but had no consistent effect on blood pressure. Treatment with oral propranolol for 24 weeks lowered cardiac output and blood pressure; total peripheral resistance did not differ from the pretreatment values. Neither acute intravenous nor chronic oral administration of the beta-blocker affected the resting plasma levels of noradrenaline and adrenaline. Long-term treatment with propranolol reduced urinary excretion of vanilmandelic acid without affecting urinary catecholamine excretion. Acute intravenous injection of propranolol decreased plasma renin activity less than did chronic oral treatment with the drug. The observed time course of plasma renin activity was compatible with the view that suppression of this enzyme contributed to the antihypertensive effect of propranolol.     

Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension

Summary A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg · day⁻¹ of nicardipine and 120 mg · day⁻¹ of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated. Cardene, Rydene and Rycardene are the Syntex trademarks for nicardipine hydrochloride     

瑞芬太尼对气管内插管时血流动力学及血糖、皮质醇的影响

目的以芬太尼作对照,观察使用瑞芬太尼行全身麻醉快速诱导窥喉和气管插管时对血流动力学的影响及血糖、皮质醇的变化。方法24例ASAⅠ-Ⅱ级的全麻患者,随机平均分为2组:瑞芬太尼组(RF).芬太尼组(F)。RF组在静注维库溴铵0.1mg/kg,异丙酚1.5mg/kg后,予瑞芬太尼1μg/kg(以生理盐水稀释为20ml,输入时间大于30s),60s后插管;F组静注芬太尼3μg/kg,维库溴铵0.1mg/kg,异丙酚1.5mg/kg,3min后插管。连续监测插管前后血流动力学及血糖、皮质醇的变化。结果R组患者插管前血压降低,与基础值比较组内差异有显著性(P<0.05),HR略减慢。插管后各项参数变化与基础值比较组内差异无统计学意义。F组患者插管前血压略降低、HR略减慢,但与基础值比较无统计学差异;插管后1,3minSBp、DBp增高;HR增快,与基础值比较组内差异有显著性(P<0.05)。且5min时DBp、HR仍显著高于基础值。两组基础HR、SBp、DBp无显著性差异。诱导后RF组SBp、DBp显著低于F组(P<0.05);RF组插管后1min的HR、SBp、DBp;插管后3min的SBp、DBp;插管后5min的DBp均显著低于F组(P<0.05)。两组血糖在插管后差异不显著。皮质醇浓度在插管后R组降低,F组则升高,两组比较,有显著性差异(P<0.05)。结论插管前静脉注入瑞芬太尼通常可较好地抑制窥喉和气管插管时的应激反应,且优?     

Pharmacokinetics after a single oral dose of bopindolol in patients with cirrhosis

Summary The plasma concentration-time curve of the hydrolysis product of bopindolol has been investigated in 14 patients with cirrhosis and in 15 healthy volunteers given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history and clinical examination or liver biopsy.The time to maximum concentration, maximum concentration and AUC of hydrolyzed bopindolol were similar in the patients and controls. However, the elimination half-life was 6.0 h in controls and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients with cirrhosis, but no correlation was found with the pharmacokinetic parameters of hydrolysed bopindolol.Although the AUC was not significantly altered in patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests impairment of its disposition in liver disease, which could lead to significant accumulation of drug during chronic dosing.     

Acute haemodynamic effects of ajmaline and prajmaline in patients with coronary heart disease

Summary Thirty patients undergoing cardiac catheterisation for coronary artery disease received parenteral ajmaline (15 patients) or prajmaline (15 patients). There were no statistically significant induced changes in left ventricular systolic or end diastolic pressures, indirect left atrial pressure, pulmonary artery mean pressure, cardiac output or left ventricular ejection fraction compared to control values. Intravenous prajmaline bitartrate in 15 patients with angina did not significantly alter work capacity, maximum exercise heart rate or systolic blood pressure compared to control values. Five patients developed transient minor conduction defects (2 LBBB, 1 RBBB, 2 prolonged PR interval): all five were also receiving long-term treatment with beta blockers and nifedipine.     

Acute haemodynamic and neurohumoral effects of intravenous nisoldipine in patients with severe congestive heart failure

Summary Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continous infusion of 0.2 g · kg^–1 · min^–1. Haemodynamic measurements were performed at baseline and after 30 min.The mean arterial pressure fell from 91 to 73 mm Hg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn · s · cm^–5.The cardiac index (2.2 to 2.71 · min^–1 · m^–2, and stroke volume index (25 to 33 ml · m^–2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats · min^–1. Plasma renin activity and norepinephrine concentration did not change significantly.The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology.     

乙型肝炎肝硬化肝性脑病胱抑素C与ABO血型相关性研究

目的：探讨乙型肝炎肝硬化肝性脑病（肝性脑病组）血清胱抑素C（CysC）与ABO血型相关性。方法2008年1月至2014年10月采用ABO/RhD血型定型检测试剂卡对228例乙型肝炎肝硬化合并肝性脑病患者进行ABO血型鉴定,采用PCR扩增仪测定患者HBV DNA载量,免疫比浊法测定两组血清CysC水平,采用Child-Pugh分级评价患者肝功能,并与220例健康对照组进行对比。结果肝性脑病组A型血比例为35.09%,高于对照组的23.63%,差异有统计学意义（P＜0.05）。肝性脑病B型、O型、AB型比例分别为21.05%、22.81%、17.54%,而对照组分别为28.18%、27.27%、20.91%,差异无统计学意义（P＞0.05）。肝性脑病组患者AB血型患者Child-Pugh分级,C级比例为52.50%,高于A型、B型、O型（分别为25.00%、20.83%、23.08%）,差异有统计学意义（P＜0.05）。肝性脑病组患者中A血型患者HBV DNA载量为（1856.43±221.52）IU/ml,高于B型、O型、AB型[分别为（389.22±78.56）IU/ml、（412.58±70.25）IU/ml、（404.26±68.55）IU/ml],而A型、AB型患者血清CysC水平分别为（5.263±0.752）mg/L、（5.201±0.812）mg/L,高于B型及O型[分别为（0.782±0.028）mg/L、（5.201±0.812）mg/L]。结论 A型血乙型肝炎肝硬化患者更容易并发肝性脑病,AB血型患者肝硬化病情较其他血型严重,血清CysC水平升高可能是这两种血型病情较重的原因,因此临床应加强对A型、AB型人群乙型肝炎防治。     

Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60  min after oral administration of 4  mg molsidomine then 15  min after intravenous administration of 15  mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (−7.9%, P <0.01), cardiac output (−7.3%, P <0.01), pulmonary wedged pressure (−45.8%, P <0.05) and hepatic venous pressure gradient (−11.7%, P <0.01). Propranolol decreased heart rate (−21%, P <0.01), further decreased cardiac output (−20.6%, P <0.01) and hepatic venous pressure gradient (−10.5%, P <0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (−8%, P <0.01), heart rate (−19%, P <0.01), cardiac output (−26.5%, P <0.01) and hepatic venous pressure gradient (−21%, P <0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.     

Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers

Summary The effects of nitroglycerin, infused intravenously at 3.4 and 7.5 µg/min over 30 min, on haemodynamic parameters were determined in the morning and the afternoon in a randomized, placebo-controlled study in 5 healthy volunteers. The mean steady-state concentrations of nitroglycerin reached in the plasma during the infusions of 3.4 and 7.5 µg/min were 0.35±0.06 ng/ml and 0.64±0.22 ng/ml, respectively. Wide inter-individual variation was noted. The nitroglycerin-induced increase in the orthostatic rise in heart rate and the change in digital-pulse-wave morphology roughly paralleled the plasma concentration, whereas the reduction in systolic blood pressure in the upright position was still evident 15 mins after the infusion, i.e. when nitroglycerin was no longer measurable in plasma. No significant diurnal variation in vascular sensitivity to the vasodilative action of nitroglycerin was demonstrable. The change in pulse-wave morphology resulting from the reduction in peripheral resistance (shift of the dicrotic wave in the descending limb towards the base-line) proved to be the most sensitive haemodynamic parameter.