小剂量心得安加川芎嗪预防食管静脉曲张破裂出血的实验与临床研究

目的探讨小剂量心得安与川芎嗪联用预防肝硬变食管静脉曲张破裂出血(EVB)复发的疗效、副反应及其作用机制.方法在用药前后采用血管插管法对8只肝硬变犬血流动力学指标进行检测.在临床上对治疗组(n=38,po心得安10 mg+川芎嗪50 mg,3次/d)和安慰剂组(n=36,服维生素B110 mg+维生素PP 50 mg,3次/d)进行前瞻性对照研究,随访2 a,并用彩色多普勒超声仪监测其门脉系统血流动力学变化.结果小剂量心得安与川芎嗪联用可使肝硬变犬WHVP,HVPG,Rpv及Ppv明显降低,对HR,MAP无明显影响.用药4 wk后治疗组患者Qpv,Qsv,Dpv,Dsv及Qaz均显著下降(分别为1439±494 vs1152±387,948±436 vs 529±362,1.43±0.25vs1.36±0.28,1.20±0.24vs0.85±0.16,0.94±1.18vs0.71±1.04,P＜0.05/0.01);随访2 a,安慰剂组再出血率和死亡率均显著高于治疗组(P＜0.05);临床上未见明显副作用.结论小剂量心得安与川芎嗪联用预防EVB复发是安全有效的.     

普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的保护作用及其机制的研究

目的:探讨普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的预防作用及其机制。方法:50只Wistar雄性大鼠经高脂喂养17周,制成动脉粥样硬化模型。随机分为对照组、肾上腺素组、普萘洛尔小剂量组、普萘洛尔中剂量组、普萘洛尔大剂量组,每组10只。所有大鼠在继续高脂喂养基础上,对照组皮下注射生理盐水0.5ml/d;肾上腺素组予肾上腺素0.5mg.kg-1.d-1皮下注射;普萘洛尔小、中、大剂量组分别予普萘洛尔2.5mg.kg-1.d-1、5mg.kg-1.d-1、7.5mg.kg-1.d-1灌胃,0.5h后皮下注射肾上腺素0.5mg.kg-1.d-1。分组处理1周,处死全部大鼠,取主动脉粥样斑块用免疫组织化学方法检测巨噬细胞(CD68)浸润及MMP-9表达。结果:肾上腺素组,CD68阳性细胞浸润及MMP-9的表达显著高于对照组;普萘洛尔小、中、大剂量组,CD68阳性细胞浸润程度及MMP-9的表达较肾上腺素组显著减少,且减少程度与普萘洛尔剂量呈正相关。结论:普萘洛尔可以减轻肾上腺素刺激后大鼠动脉粥样硬化斑块内巨噬细胞的浸润及其MMP-9表达,有延缓肾上腺素促大鼠动脉粥样硬化斑块进展的作用。     

心得安试验对功能性ST-T改变的临床价值

目的探讨口服心得安试验对功能性ST—T改变的临床价值。方法分析86例40岁以上伴有心悸、胸闷、气短症状,静息心电图有ST段水平或下斜型压低,T波低平的患者,通过口服心得安药物20mg,分别在30、60、90、120min描记心电图观察其变化。结果口服心得安20mg60min后描记心电图,86％女性S—T段恢复正常,呈阳性改变,与男性组相比有明显差异性（P〈0．05）;与男性不同年龄组相比,随年龄增加阳性率逐渐降低,无明显差异性（P〉0．05）。结论86％以上的女性ST—T改变是植物神经功能紊乱所致,为功能性改变,与器质性ST-T改变无相关性和必然联系,对冠心病诊断敏感性为92．3％．特异性为90．6％．阳性预测价值为88．9％．     

Comparative evaluation of drug release from aged prolonged polyethylene oxide tablet matrices: effect of excipient and drug type

Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug.     

"阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤的疗效评价

目的：采用"阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤,探讨其疗效及安全性。方法：治疗前对98例婴幼儿混合型和深层血管瘤患儿进行全面评估,并行心电图、心脏彩超、血糖、肝功能、肾功能、心肌酶和血常规检查,排除禁忌证后均给予"阶梯治疗方案"口服普萘洛尔治疗,剂量从0.5mg·kg^-1·d^-1逐渐增加至4.0 mg·kg^-1·d^-1,分3次口服,服药前和服药后1和2h监测心率,动态观察瘤体大小、质地、颜色等变化及患儿有无相关不良反应,每个月复诊,按4级评分法进行疗效评价。结果：服药后,98例患儿瘤体均出现不同程度颜色变浅或质地变软,普茶洛尔剂量增至4.0 mg·kg^-1·d^-1后瘤体性质变化最快。疗效评价,Ⅳ级（优）84例（85.71%）,Ⅲ级（好）2例（2.04%）,Ⅱ级（中）4例（4.08%）,Ⅰ级（差）8例（8.16%）。混合型血管瘤的疗效优于深层血管瘤（P<0.05）。74例血管瘤患儿痊愈时间为6个月。主要不良反应,心率下降5例（5/98,5.10%）,嗜睡3例（3/98,3.06%）,腹泻7例（7/98,7.14%）,食欲不振1例（1/98,1.02%）,抽搐2例（2/98,2.04%）,给予对症处理后均恢复正常。停药后2个月复发4例,继续服药仍然有效。结论："阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤疗效明显,且无严重不良反应发生。     

普萘洛尔致犬急性心衰模型的方法学研究

目的探讨普萘洛尔对比格犬诱导急性心力衰竭模型的可行性。方法静脉推注普萘洛尔诱导急性心力衰竭,静脉滴注普萘洛尔维持心衰,股动脉插管监测血流动力学指标变化,电磁流量计测量心输出量。结果与造模前基础值相比,普萘洛尔造模后心率、动脉收缩压、动脉舒张压、平均动脉压、左室内压下降速度和左室收缩压均下降(P<0.05~0.01),左室舒张末期压上升(P<0.01),左室内压上升速度和心输出量分别下降51.7%、41.1%(P<0.01),达到心衰标准,且上述指标在2 h内保持稳定。结论普萘洛尔建立急性心力衰竭模型稳定可行。     

Effects of high ambient temperature on parasympathetically mediated cardiovascular reflexes in normal man

AIMS: To examine the effects of high ambient temperature ('heat stressor') on parasympathetically mediated cardiovascular reflexes (power of respiratory sinus dysrhythmia; change in heart rate elicited by change in posture from lying to standing ['30 : 15 ratio']). METHODS: Twelve healthy male volunteers participated in four weekly sessions, each of which was associated with one treatment condition (placebo at an ambient temperature of 22 degrees C; propranolol 40 mg at 22 degrees C; placebo at 40 degrees C; propranolol 40 mg at 40 degrees C), according to a balanced double-blind design. Heart rate was recorded by ECG, finger tremor (7-12 Hz) with an accelerometer strapped to the middle finger of the nondominant hand, and sublingual temperature by a mercury thermometer. Power of finger tremor and the variations of the R-R intervals of the ECG were obtained from Fourier transformations of the data. Data were analysed by analysis of variance, with repeated measures using a significance criterion of P < 0.05; individual comparisons of active treatment with placebo and of data obtained at 40 degrees C with those obtained at 22 degrees C were made with Fisher's Least Significant Difference test. RESULTS: Heart rate was increased by the heat stressor, and this increase was abolished by propranolol. The heat stressor reduced the power of respiratory sinus dysrhythmia and the 30 : 15 ratio, and increased the power of physiological finger tremor. Propranolol did not affect heat stressor-induced changes in the parasympathetic cardiac reflexes, but reduced the heat stressor-induced enhancement of finger tremor. CONCLUSIONS: The increase in the power of physiological finger tremor at high ambient temperature is consistent with sympathetic activation, whereas the reduction in the power of respiratory sinus dysrhythmia and 30 : 15 ratio indicates a decrease in parasympathetic activity. These results demonstrate that high ambient temperature may induce vagal withdrawal in the heart.     

PLASMA PROPRANOLOL CONCENTRATION IN PATIENTS WITH ANGINA AND ACUTE MYOCARDIAL INFARCTION

1. Plasma levels of propranolol were measured fluorometrically in patients with angina pectoris and in patients admitted to the Coronary Care Unit with acute myocardial infarction. 2. In thirty patients with stable angina pectoris, plasma propranolol levels varied almost linearly with doses between 10 and 120 mg during 6-hourly chronic oral administration. Plasma levels greater than 100 ng/ml produced 70–80% reduction in the tachycardia induced by strenous exercise on a treadmill. 3. In nineteen patients with acute myocardial infarction given oral propranolol, 20 mg 6-hourly, peak as well as trough plasma levels of the drug increased progressively but remained below 100 ng/ml in all except two patients during the first 24 h after their admission to the Coronary Care Unit. 4. The data suggest that the use of low and fixed doses of propranolol may not produce adequate plasma levels or significant β-adrenoceptor blockade in the early stages of acute myocardial infarction in man.