条件刺激对大鼠心率的影响

条件刺激(CS)可使动物心率发生改变,在CS之初,大鼠心率增加;但在CS之末,心率呈下降之态。用β受体阻断剂心得安后,心率增加的现象被取消,但对CS末的心率减慢没有响影。提示CS之初的大鼠心率变化可能主要取决于交感系统的活动。     

Kinetics and cardiac effects of propranolol in humans

Summary Six healthy volunteers received single 20-mg intravenous (IV) and 80-mg oral doses of propranolol on two occasions in random sequence. Serum propranolol concentrations were determined by gas chromatography in multiple samples drawn during 24 h after each dose. Mean (±SE) kinetic variables for IV propranolol were: elimination half-life (t1/2), 5.3 (±0.6) h; volume of distribution, 2.3 (±0.3) l/kg; total clearance, 4.9 (±0.3) ml/min/kg; predicted extraction ratio, 0.23 (±0.02). After single oral doses, t1/2 (3.8±0.2 h) tended to be smaller than after the IV dose, and actual systemic availability (0.60±0.07) was less than that based on the predicted extraction ratio. During multiple oral dosage (80 mg every 12 h), observed steady state serum levels (47±5 ng/ml) tended to be less than those predicted based on the single oral dose (61±5 ng/ml), thus providing no evidence for reduced propranolol clearance at steady-state. Echocardiographic measurements of left ventricular performance (posterior wall velocity, diastolic dimensions) made during the single-dose oral study indicated significant impairment of function; impairment was maximal at 3 h post-dosage, and corresponded to the time of the peak serum propranolol concentration (341 ng/ml).Supported in part by Grant Oc 10/6-3 from Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, FRG; and by Grant MH-34223 from the United States Public Health Service     

Effect of training on the resting heart rate of rats

Summary Adult male rats were progressively trained 5 days/week on a motor-driven treadmill. The training period lasted 12 weeks and consisted of 60 min/day of wind-sprints and endurance work. No significant difference in resting heart rates was observed between the control and exercise groups during week 1 (394±7 vs. 388±5). However, at week 12 the exercise group had a lower resting heart rate (359±6 vs. 331±4). Heart rates observed following saline, propranolol, atropine, and propranolol plus atropine injections were lower in the exercise group in all cases. The difference in heart rates between the control and exercise groups was 19 beats/min following propranolol plus atropine which was less than the 28 beats/min difference observed under control conditions. With atropine and then with propranolol the differences were 33 and 27 beats/min. These heart rate differences were observed without the presence of cardiac hypertrophy as assessed from ventricle weights.Our data indicate that the bradycardia resulting from exercise training is due primarily to changes other than neural influences on the heart.Supported by a USPHS Career Development Award HL 00052-01     

纳洛酮对急性冠脉闭塞后家兔心功能的影响及其机制的研究

本实验观察了阿片受体拮抗剂纳洛酮对急性冠脉闭塞家免心肌舒缩性能的影响以及这种影响和肾上腺素能β受体的关系。结果表明:在家兔急性冠脉闭塞早期,纳洛酮可显著增强心肌舒缩性能,改善心功能;β受体阻滞剂心得安可取消纳洛酮的这种作用。说明纳洛酮增强急性冠脉闭塞家兔心肌舒缩性能的作用与肾上腺表能神经活动密切相关。     

32P敷贴联合普萘洛尔治疗儿童大面积皮肤毛细血管瘤

目的 探讨32P敷贴联合普萘洛尔治疗儿童大面积皮肤毛细血管瘤的临床疗效.方法 将45例大面积毛细血管瘤患儿分为两组,进行前瞻性研究.对照组20例,其中≤3岁儿童草莓状血管瘤10例、＞3岁儿童鲜红斑痣10例,接受常规32P敷贴治疗.观察组25例,其中≤3岁儿童草莓状血管瘤10例、＞3岁儿童鲜红斑痣15例,接受32P敷贴联合普萘洛尔治疗.对比两组不同类型血管瘤、≤3岁儿童与＞3岁儿童的治疗效果及不良反应.统计计数资料采用x2检验和零反应检验,以P ＜0.05为差异有统计学意义.结果 对照组与观察组总有效率分别为80.0％与88.0％(P＞0.05);两治疗组中≤3岁儿童血管瘤有效率分别为90.0％与100.0％(尸＞0.05);但两治疗组中＞3岁儿童鲜红斑痣有效率分别为40.0％与80.0％,差异有统计学意义(P＜0.05).对照组单用32P敷贴在≤3岁儿童与＞3岁儿童有效率分别为90.0％与40.0％,差异有统计学意义(P＜0.05),观察组用32P敷贴联合普萘洛尔在≤3岁儿童与＞3岁儿童有效率分别为100.0％与80.0％,差异无统计学意义(P＞0.05).两组发生湿性皮炎分别为25.0％与40.0％,发生色素脱失分别为75.0％与84.0％,差异均无统计学意义(P＞0.05);发生心率减慢在≤3岁儿童与＞3岁儿童分别为50.0％与40.0％,差异无统计学意义(P＞0.05).结论 32P敷贴联合普萘洛尔治疗难治性大面积血管瘤,治疗方法简单、安全,疗效较好.但要密切注意32P、普萘洛尔两者不良反应的发生及处理.     

普萘洛尔、酚妥拉明对由去甲肾上腺素诱导的家兔肠系膜微血管运动的影响

应用显微录像静画步进法观察家兔肠系膜局部施加去甲肾上腺素（NA）后，诱寻出微动脉周期性、节律性的血管运动及静脉注入普萘洛尔、酚妥拉明对其产生的影响，以期探讨血管运动产生机制及其与α－，β－肾上腺素受体的关系。结果：在家兔颈动脉平均血压为11．40±0．89kPa的条件下，局部施予NA0．8μg于肠系膜观察域，引起微动脉的血管运动，其频率：0．109±0．006Hz，振幅：5．51±0．42μm。同一视野的微静脉和毛细血管未出现血管运动。血管运动的振幅在同一支微动脉上分布不均，呈节段性。普萘洛尔0．1mg／ml·kg-1、0.5mg／ml·kg-1组的内径、血压、血管运动频率及振幅无明显改变，1．0mg／ml·kg-1组的血压无明显变化，内径减小，血管运动频率增加，振幅减小。静脉注入酚妥拉明0．5mg／ml·kg－1及1．0mg／ml·kg-1，颈动脉血压降低，血管内径增加，血管运动频率减少，振幅降低，血管运动被抑制。结论：上述结果表明生理条件下，局部施加NA可以诱导出家兔肠系膜微动脉血管运动，并且血管运动的发生与NA及α－，β-肾上腺素受体有一定关系。     

纤溶系统激活的实验研究—儿茶酚胺对纤溶活性的影响

用不同浓度儿茶酚胺灌流大鼠下肢血管床,观察它们对血管内皮细胞释放纤溶酶原激活剂(PA)的作用。结果显示,同样浓度(25μM)儿茶酚胺所引起的PA释放效应以肾上腺素为最强,去甲肾上腺素次之,异丙基肾上腺素作用最弱,PA活性分别是0.202±0.038,0.117±0.006,0.097±0.007(U/ml,(?)±SE)。β肾上腺素能受体阻断剂心得安完全拮抗异丙基肾上腺素诱导PAL活性升高,部分抑制去甲肾上腺素、肾上腺素的作用。α、β肾上腺素能受体阻断剂(酚妥拉明 心得安)协同作用时,肾上腺素、去甲肾上腺素的这种PA活性升高效应基本抑制。本文还发现,剧烈运动产生应激反应时血浆去甲肾上腺素含量明显升高,为2.45±0.45(ng/ml,(?)±SE),与对照值(0.88±0.20)比P<0.01。与此同时伴随纤溶活性显著增加。实验结果提示:外源性儿茶酚胺诱导PA释放效应主要经由β肾上腺素能受体介导,α肾上腺素能受体涉及部分作用,内源性儿茶酚胺水平升高可引起纤溶活性增加。     

普萘洛尔治疗并发溃疡婴幼儿血管瘤11例的临床观察

目的评价普萘洛尔治疗婴幼儿并发溃疡血管瘤临床疗效和安全性。方法 11例并发溃疡的婴幼儿血管瘤患者口服普萘洛尔,起始剂量每天1.0mg/kg,12小时给药一次;每天递增0.5mg,至第3天以后维持每天2.0mg/kg,连续服用3～5个月。溃疡创面从治疗开始每日换药一次。每周复诊,动态观察和记录血管瘤溃疡创面情况以及瘤体大小、质地、颜色的变化。结果 11例患儿随访7～10月,8例瘤体缩小75%～100%,3例缩小50%～75%。血管瘤溃疡创面均在2～3周内愈合。发现心率减慢、腹泻、溢奶、睡眠改变等不良反应,均未需做特殊处理,2周内好转,未发现严重不良反应。结论口服小剂量普萘洛尔治疗婴幼儿并发溃疡血管瘤,能使溃疡创面在短期内愈合,并能使血管瘤体明显缩小,不良反应轻微。     

β受体阻滞剂治疗婴幼儿血管瘤的研究进展

婴幼儿血管瘤（IH）是婴幼儿期最常见的良性肿瘤,大部分病变可自然消退,多以随访观察为主,但对可引起严重并发症或功能障碍的中、高风险IH仍主张尽早干预及治疗。普萘洛尔为非选择性β受体阻滞剂,自2008年开始应用于IH治疗后经大量临床实验及系列研究疗效得到验证,目前已成为IH治疗的一线药物。随着人们对IH认识的进一步深入及普萘洛尔相关治疗机制的探索,近年来其他β受体阻滞剂类药物治疗IH的报道逐渐增多,其在IH的应用范围逐渐扩大,药物选择相应增多。本文简要综述目前β受体阻滞剂应用于IH治疗的相关进展,进一步探究其疗效及安全性,为IH临床治疗提供更多选择及参考依据。     

法乐四联症心肌纤维结构变化与心功能关系研究

目的　探讨法乐四联症心肌纤维肥大的程度对心功能与术后恢复的影响。方法　对 80例法乐四联症患者右室流出道心肌组织切片改变观察及心肌纤维直径测定 ,结合临床术前彩超测定心功能参数以及右心导管测定参数进行分析。结果　心肌纤维肥大程度与心功能指标有一定的关系。一部分四联症病例心肌纤维发生增生肥大 ,肥大的程度对射血分数无影响 (P >0 0 5 ) ,但与心肌每搏量和年龄有十分显著的相关关系 (P <0 0 1) ,并对术后恢复有一定的影响。结论　法乐四联症心肌纤维形态改变随年龄增长而加重 ,提示在条件允许的情况下 ,应尽早手术为宜     

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in na?ve T-helper (CD4+CD62L+; P<0.049) and na?ve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.     

Influence of propranolol coadministration or cigarette smoking on the kinetics of desmethyldiazepam following intravenous clorazepate

Summary The influence of propranolol coadministration or of cigarette smoking on the kinetics of desmethyldiazepam following a single 20-mg intravenous dose of clorazepate dipotassium was evaluated in healthy volunteers. In Study One, intravenous clorazepate was given once in the control condition, and again during coadministration of propranolol, 80 mg twice daily. Compliance with the prescribed propranolol regimen was verified by measurement of serum propranolol concentrations (mean, 37 ng/ml). In control vs propranolol treatment conditions, there was no significant difference in desmethyldiazepam volume of distribution (1.27 vs 1.23 liters/kg) or in free fraction in serum (1.83 vs 1.80% unbound). There was a small although statistically significant prolongation of desmethyldiazepam half-life (55 vs 61 h,P<0.05) and reduction in clearance (0.281 vs 0.247 ml/min/kg,P<0.02) attributable to propranolol. In Study Two, desmethyldiazepam kinetics were compared in eight cigarette smokers (mean, 19 cigarettes/day) and in 11 nonsmoking controls matched for age, sex, and body weight. There was no significant difference between controls and cigarette smokers in desmethyldiazepam volume of distribution (1.29 vs 1.34 liters/kg), elimination half-life (55 vs 59 h), clearance (0.284 vs 0.276 ml/min/kg), or free fraction in serum (1.96 vs 1.92% unbound). Thus, propranolol slightly although significantly impairs the clearance of desmethyldiazepam and prolongs its halflife. Cigarette smoking has no apparent influence on desmethyldiazepam kinetics.Supported in part by grants Oc 10/6–4 from the Deutsche Forschungsgemeinschaft and grants MH-34223 and AG-00106 from the United States Public Health ServicePart of doctoral thesis J. Weinbrenner, Bonn 1986     

The left retro-aortic brachiocephalic vein: morphologic data and diagnostic ultrasound in 27 cases

A left retro-aortic brachiocephalic vein is a rare anatomic entity. A retrospective study was made of 5218 congenital cardiopathies treated between 1982 and 1998 in a medico-surgical department of paediatric cardiology. A left retro-aortic brachiocephalic vein was demonstrated in 27 patients, i.e. an incidence of 0.5%. The chief cardiopathy in these patients was a tetralogy of Fallot in 25 cases (93%). Among these 25 cases of Fallot’s tetralogy the aortic arch was rightsided in 19 cases (70%). The paraclinical diagnosis of this anomaly was facilitated by ultrasonography, provided it was sought for. In this series 6 cases (22%) were discovered during surgery without previous ultrasound diagnosis. The embryological origin of the left retro-aortic brachiocephalic v. differs from that of the venous trunk in its classical anatomic form. It derives from the inferior (but not superior) transverse plexuses, connecting the two anterior cardinal veins. One of the main consequences of this anomaly is its possible confusion with other vascular structures, particularly the right pulmonary artery. Such confusion may give rise to inappropriate surgical procedures. The differential diagnosis is facilitated by the use of the Doppler the venous flow is biphasic and regulated by respiration, whereas the Doppler recording from a pulmonary artery is that of a characteristic systolic arterial flow.     

The effect of propranolol on whole-body microvibrations during examination stress

Summary Whole-body microvibrations (MV) in three dimensions were measured in 51 volunteers, all medical students, 26 without and 25 with beta-receptor blockade (propranolol), immediately before a practical physiology examination and during the ensuing vacation. Propranolol impeded the increase in MV values in all three axes, significantly those in the z axis (vertical), the differences in MV values between the two measurements being minimal in the beta-receptor blocked group. On the other hand, propranolol enhanced MV in the x axis (anteroposterior) and the y axis (transverse), the y axis difference being significant only in females. Propranolol obviously relieves examination stress: the majority of candidates (52%) felt “quieter≓ in the examination with than in other similar situations without beta-receptor blockade. Propranolol was, however, without effect on the examination results. The rectified impulse in the z axis when related to body weight (Jz) correlates linearly with the calculated cardiac output. Propranolol, however, reduced cardiac output more than Jz, pointing to a Jz component non-sensitive to beta-receptor blockade. The part played by muscle tonus, mainly reflected in the y axis, thus remains unknown. The large and slow oscillations in the x and y axes, observed particularly in beta-receptor blocked females, might be attributed to diminution in standing ability.     

The protective roles of mitochondrial ATP-sensitive potassium channels during hypoxia-ischemia-reperfusion in brain

Although the coadministration of lidocaine with propranolol interferes with the metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In this report, we investigate whether propranolol can potentiate the effect of lidocaine. Rats received spinal anesthesia with lidocaine co-injected with propranolol. After intrathecal injections of drugs in rats, three neurobehavioral examinations (motor function, proprioception, and nociception) were performed. We showed that lidocaine and propranolol elicited a spinal blockade in motor function, proprioception, and nociception. Propranolol at the dose of 0.82 μmol/kg produced no spinal anesthesia. Co-administration of lidocaine [50% effective dose (ED₅₀) or ED₉₅] and propranolol (0.82 μmol/kg) produced greater spinal anesthesia than lidocaine (ED₅₀ or ED₉₅), respectively. These preclinical findings demonstrated that propranolol and lidocaine displayed spinal anesthesia. When combined with propranolol, lidocaine elicited a supra-additive effect of spinal anesthesia.     

帕罗西汀合并普萘洛尔治疗焦虑症的对照研究

目的观察帕罗西汀合并普萘洛尔治疗焦虑症的临床疗效和不良反应。方法把205例患者随机分为研究组(帕罗西汀合并普萘洛尔)105例,对照组(帕罗西汀)100例,治疗6周。采用汉密尔顿焦虑量表(HAMA)、临床总体评价量表(CG I)评定临床疗效,采用不良反应量表(TESS)评定安全性。结果研究组和对照组的总有效率分别为87.8%和75.5%,两组差异有显著性(χ2=5.32,P0.05),且研究组的起效时间早于对照组。研究组2、4、6周时HAMA减分率均高于对照组,并有显著性差异(F=14.58,P0.01)。研究组头痛、心动过速、震颤等不良反应较对照组少而轻。结论帕罗西汀合并普萘洛尔治疗广泛性焦虑症具有良好的疗效和安全性,且疗效和安全性优于单独应用帕罗西汀。     

Structural and mutational analysis of antiquitin as a candidate gene for Menière disease

A 20‐year‐old female with trisomy 18 is described. Survival past infancy is rare in this disorder. Little is known concerning the factors that contribute to prolonged survival with this syndrome. This case provides an opportunity to review the management of older children and young adults with trisomy 18. © 2002 Wiley‐Liss, Inc.     

Effect of beta-adrenergic blockade on plasma lactate concentration during exercise at high altitude

Summary When unacclimatized lowlanders exercise at high altitude, blood lactate concentration rises higher than at sea level, but lactate accumulation is attenuated after acclimatization. These responses could result from the effects of acute and chronic hypoxia on -adrenergic stimulation. In this investigation, the effects of -adrenergic blockade on blood lactate and other metabolites were studied in lowland residents during 30 min of steady-state exercise at sea level and on days 3, 8, and 20 of residence at 4300 m. Starting 3 days before ascent and through day 15 at high altitude, six men received propranolol (80 mg three times daily) and six received placebo. Plasma lactate accumulation was reduced in propranolol- but not placebo-treated subjects during exercise on day 3 at high altitude compared to sea-level exercise of the same percentage maximal oxygen uptake ( ). Plasma lactate accumulation exercise on day 20 at high altitude was reduced in both placebo- and propranolol-treated subjects compared to exercise of the same percentage performed at sea level. The blunted lactate accumulation during exercise on day 20 at high altitude was associated with reduced muscle glycogen utilization. Thus, increased plasma lactate accumulation in unacclimatized low-landers exercising at high altitude appears to be due to increased -adrenergic stimulation. However, acclimatization-induced changes in muscle glycogen utilization and plasma lactate accumulation are not adaptations to chronically increased -adrenergic activity.     

De novo inverted interstitial (“mirror”) duplication of chromosome 8(q13→q24.1) in a liveborn male

We report on a newborn boy with a de novo inverted interstitial duplication of chromosome 8(q13→q24.1). This form of cytogenetic abnormality, in which a mirror image interstitial duplication has occurred, is exceedingly rare. Review of the literature and mechanisms to explain the origin of this type of chromosome aberration are presented. A review of the findings from individuals with partial dup(8q) demonstrate remarkable similarity to the infant we describe.     

The comparison of esophageal variceal ligation plus propranolol versus propranolol alone for the primary prophylaxis of esophageal variceal bleeding

Background/Aims

To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding.

Methods

A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2.

Results

EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000).

Conclusions

EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.