比索洛尔对轻中度高血压心率及心率变异性的影响

目的观察比索洛尔对轻中度高血压在心率和心率变异性上的效应。方法63例轻中度高血压患者随机分为两组比索洛尔组接受比索洛尔片5~10mg,4周;对照组则接受硝苯地平控释片20mg,4周。治疗前后均作动态血压(ABPM)监测,并作心率变异性分析。结果两组治疗后SBP及DBP均有明显的下降(P<0.01),组间比较无明显差异(P>0.05)。比索洛尔组治疗后HR从(81±9)b/min下降到(68±7)b/min,有明显减慢心率的作用(P<0.01);而对照组则无此效应。两组治疗后心率变异性分析显示各项指标均有改善,以比索洛尔组为优(P<0.05)。结论比索洛尔能有效地降低血压,减慢心率,改善高血压患者的心率变异性,从而防止高血压患者心血管事件发生。     

Effects of in vivo treatment with isoprenaline or prenalterol on beta-adrenoceptor mechanisms in the heart and soleus muscle of the cat

Summary The full agonist isoprenaline (5.3–6.6 nmol/kg min) and the partial -adrenoceptor agonist prenalterol (10.6–13.3 nmol/kg · min) were administered to cats continuously via osmotic minipumps (i.p.). After seven days the functional and adenylate cyclase responsiveness to the agonists, as well as the -adrenoceptor-binding characteristics, were studied in cardiac and soleus muscle preparations in vitro.After isoprenaline pretreatment, the papillary muscles and soleus muscle strips were 15–18 times less sensitive to isoprenaline compared with muscles from control cats. The stimulatory potency (pD₂) of prenalterol in the papillary muscle was not changed significantly. The affinity of the agonists to the -adrenoceptors was unaffected in both tissues by the pretreatment, but the densities of -adrenoceptors were significantly reduced, by 36% (myocardium) and 47% (soleus) respectively. In the cat papillary muscle the intrinsic sympathomimetic activity (ISA) of prenalterol on contractile parameters was reduced from 84 (T _max), 69 (dT/dt _max) and 71% (dT/dt _min) in control animals, to 33, 22 and 28%, respectively in the animals pretreated with isoprenaline.Prenalterol pretreatment did not induce any marked changes, either in the stimulatory potency or affinity of the agonists in the two tissuer or in the maximal response (ISA) of prenalterol in the papillary muscle.The marked reduction in the stimulatory potency of isoprenaline and the reduced ISA of prenalterol in the myocardium after isoprenaline pretreatment can not be explained by the reduction in -adreoceptor density alone. Since the affinity to the -adrenoceptors is unaffected, a reduced efficiency in the signal transmission must be the main cause. This alteration in signal transmission seems to be an event located distal to adenylate cyclase, since the relative decrease in the enzyme activity is even less than the loss of -adrenoceptors in both the myocardium and soleus muscle.The present results demonstrate that the effects on -adrenoceptors and functional responsiveness are different after prolonged treatment with a full -adrenoceptor agonist and a partial agonist, such as prenalterol.Some of these data were presented at the 66th Annual Meeting of the Federation of American Societies for Experimental Biology, April 15–23, 1982 New Orleans, USA     

The effect of nipradilol on the isoproterenol-induced depression of contractions in the cat soleus muscle

The effect of nipradilol on the isoproterelol-induced depression of contractions of the soleus muscle of the anesthetized cats was studied. Isoproterenol (0.3 microg/kg) injected intravenously decreased the tension and degree of fusion of incomplete tetanic contractions of the soleus muscle of the anesthetized cats. The effect of isoproterenol was blocked by nipradilol (> or = 3 microg/kg), desnitro-nipradilol (> or = 10 microg/kg) and propranolol (> or = 10 microg/kg), but not by nitroglycerin (10-100 microg/kg). Nipradilol (30 microg/kg) and desnitronipradilol (300 microg/kg) almost completely antagonized the depressor effects of isoproterenol. These results coupled with evidence that nipradilol does not penetrate the blood-brain barrier indicate that nipradilol exerts an anti-tremor action by blocking peripheral beta2-adrenoceptors.     

Actions of some sympathomimetic bronchodilator and beta-adrenoceptor blocking drugs on contractions of the cat soleus muscle

1. (-)-Isoprenaline, salbutamol, orciprenaline and quinterenol injected intravenously decreased the tension and degree of fusion of incomplete tetanic contractions of the soleus muscle of the anaesthetized cat.2. Under the most sensitive conditions, the smallest effective dose of (-)-isoprenaline was of the order of 0.01 mug/kg intravenously. Salbutamol was usually 6-10 times, orciprenaline 20-30 times and quinterenol about 35 times less potent than isoprenaline. The effects of salbutamol were about 1.6 times, of orciprenaline about 1.8 times and of quinterenol more than 20 times as long lasting as those of (-)-isoprenaline.3. The effects of the sympathomimetic amines were blocked by propranolol, H56/28, H35/25 and butoxamine but not by ICI 50172. The combined results with agonists and antagonists indicate that the receptors involved can be classified as of the beta(2) type.4. The effect of the amines on the cat soleus muscle appears to be analogous to that causing enhancement of physiological tremor in man, which suggests that skeletal muscle tremor may be an occasional unwanted side effect of the use of these bronchodilators.     

通心络对心力衰竭患者左室重构及心率震荡的影响

目的探讨通心络对慢性心力衰竭患者（CHF）左室重构及心率震荡（HRT）的影响。方法 55例老年慢性心衰患者为通心络组,对照组30例。通心络组在常规抗心衰治疗的基础上加用通心络治疗30d。在治疗前后分别测定血浆脑钠肽（BNP）、HRT指标[震荡初始（TO）和震荡斜率（TS）]、左室射血分数（LVEF）、左室舒张末径（LVEDD）的变化。结果通心络组总有效率为94.55%。通心络治疗后TO、TS、LVEF、LVED、BNP较治疗前均有显著改善（P〈0.05）。结论通心络在一定程度上逆转心室重构,改善心功能。     

Effects of the enantiomers of R,S-salbutamol on incompletely fused tetanic contractions of slow- and fast-twitch skeletal muscles of the guinea-pig

1. The effects of racemic R,S-salbutamol, and its individual enantiomers have been studied on incompletely fused (sub-tetanic) contractile responses of fast- and slow-contracting isolated skeletal muscles of the guinea-pig.
2. R,S-salbutamol (2–4 μM) decreased the peak force of sub-tetani in the slow-contracting soleus muscle and increased the peak force of sub-tetani in the fast-contracting peroneus longus muscle. It also increased the force of the first twitch of sub-tetani in both muscles. The decrease in the peak force of sub-tetani in the soleus muscle was due to defusion of the individual twitches caused by a shortening of their time course.
3. The effects of 4 μM of the racemate on both fast- and slow-contracting muscles were mimicked by 2 μM R-salbutamol (levalbuterol). However, 2 μM S-salbutamol was devoid of activity in both muscles.
4. We concluded that all the effects of R,S-salbutamol on guinea-pig skeletal muscles are due to the activity of the R-enantiomer. Thus there is a common enantiomeric profile for the skeletal muscle and bronchorelaxant activity of the compound.

     

Effects of morphine on central catecholamine turnover,blood pressure and heart rate in the rat

Summary In the unanaesthetized rat morphine caused increased dopamine (DA) turnover, unchanged or possibly increased central noradrenaline (NA) turnover (utilization), hypertension and tachycardia. In the anaesthetized rat, brain DA turnover was not affected, whereas the NA-turnover was decelerated, particularly in some brain regions, e.g. cerebral cortex and medulla oblongata, and hypotension and bradycardia was obtained. Both biochemical and cardiovascular effects of morphine were antagonized by naloxone. A very small dose of morphine (1 mg/kg) caused tachycardia also in the anaesthetized rat. Decerebration just inferior to the inferior colliculus abolished the cardiovascular, excitatory effects of morphine in the conscious rat, but left the circulatory, depressant actions of the drug unchanged.The morphine-induced cardiovascular effects, particularly the hypotension and bradycardia in the anaesthetized animal, are suggested to be related to, or mediated by, the effects of the drug on brain NA-mechanisms, especially in view of several similarities between morphine and the antihypertensive -adrenergic agonist clonidine. Whereas higher brain structures appear important in the excitatory, circulatory effects of morphine, structures below the decerebration level, e.g. medulla oblongata, appear primarily involved in the hypotension and bradycardia obtained in the anaesthetized animal. Possibly, morphine has a diphasic dose-response curve with respect to cardiovascular function and, by inference, on brain noradrenergic mechanisms.     

糖尿病、高血压与血脂紊乱对心率变异性的影响

目的 探讨糖尿病、高血压、血脂紊乱对心率变异性（HRV）的影响。方法 对单纯33例糖尿病、30例高血压及76例血脂紊乱患者，进行24h HRV时域、频域分析，同时与34例无明显临床疾病、肥胖或超重及血脂异常的正常成人进行HRV的差异比较。结果 1．糖尿病和高血压组与正常组比较HRV各指标除FL／HL均降低（P〈0．05）；血脂异常组HRV各指标除FL／HL也均低于正常组，但仅HF有统计学差异（P〈0．05）。2．血脂异常组与糖尿病及高血压组比：反映交感神经张力的SDNN，SDANN，SDNNindex，LH均降低（P均〈0．05），而反映迷走神经张力的RMSSD、PNN50及HF也降低，仅糖尿病与血脂异常组HF有统计学意义（P〈0．05）；3．糖尿病组HRV各指标均低于高血压组，但无统计学差异。校正年龄、性别、吸烟、We，SBP，DBP，FPG，UA，FATc，Te，TG，HDL-c，LDL-c后上述差异仍存在。结论 糖尿病、高血压与血脂异常、正常人间存在HRV差异。糖尿病和高血压血脂紊乱HRV各指标减低，提示存在交感神经活性增加，迷走神经活性降低，自主神经的功能紊乱可能是糖尿病、高血压血脂紊乱患者心血管事件增加的原因之一。     

Regional vascular resistance and heart rate responses mediated through H1- and H2-histamine receptors in the unanaesthetised rabbit

The effects of histamine infusions (10—100 μg/kg/min) on heart rate and hindlimb, carotid, mesenteric and renal vascular resistance were investigated in unanaesthetised rabbits after “total” autonomic effector block to abolish reflex effects. Histamine caused a rise in heart rate that was predominately due to stimulation of H₂-receptors (blocked by metiamide). Hindlimb and carotid vascular resistance did not change significantly during histamine infusion. However, after blocking H₂-receptors with metiamide histamine infusions produced dose-related vasoconstriction in these beds while after H₁-receptor block with mepyramine histamine caused dose-related vasodilatation indicating that H₁- and H₂-receptors mediated opposite vascular effects which were of similar magnitude. By contrast, histamine infusion caused vasodilatation in both the mesenteric and renal vasculature before giving antagonists. This dilatation was mediated by both H₁- and H₂-receptors as either receptor antagonist attenuated the response. These studies suggest that H₁-receptors in the same species mediate vasoconstriction in some beds and vasodilatation in others while H₂-receptors mediate vasodilatation in all the beds studied and also account for most of the increase in heart rate.     

缬沙坦对原发性高血压患者窦性心率震荡的影响

目的观察缬沙坦对原发性高血压患者窦性心率震荡的影响。方法对符合入选标准的75例原发性高血压患者,根据超声心动图结果分为左心室肥厚组35例,左心室正常组40例;健康对照组34例共3组;均行24h动态心电图监测。计算窦性心率震荡初始值（turbulence onset,TO）与震荡斜率值（turbulence slope,TS）,比较3组之间的差异。原发性高血压患者在常规治疗基础上加用缬沙坦治疗12周后,观察各组患者治疗前后心脏超声指标（LVMI）、心率震荡参数（TO、TS）等变化。结果左心室肥厚组、左心室正常组较对照组TO增大,TS降低（P〈0.05）;左心室肥厚组较左心室正常组TO增大,TS降低（P〈0.05）,左心室肥厚组LVMI均高于左室正常组与对照组（P〈0.05）,两组原发性高血压患者经缬沙坦治疗后的TO、LVMI降低,TS升高（P〈0.05）。结论原发性高血压患者存在自主神经损害,左室肥厚者损害更加明显,缬沙坦能有效改善原发性高血压患者自主神经功能的损伤及左心室肥厚。     

美托洛尔对老年患者心功能及心率变异性的影响

目的评价美托洛尔对老年患者心功能及心率变异性(HRV)的影响。方法心血管病老年患者426例,年龄≥70岁,口服美托洛尔治疗12个月。观察治疗前、治疗12个月后BP、HR、HRV(340例窦性心律患者)、左室收缩末期容积(LVESV)和舒张末期容积(LVEDV)、左室射血分数(LVEF)和心排血量(CO)的变化。结果与治疗前比较,治疗后BP、HR明显降低(P<0.05),LVEDV及LVESV明显降低[(173.22±45.42)ml vs.(158.55±40.34)ml和(150.34±54.14)mlvs.(134.65±44.02)ml](P<0.05)],而LVEF和CO明显增加[(56.16±3.26)%vs.(60.25±4.05)%和(4.2±1.2)L vs.(5.4±1.9)L](P<0.05)]。HRV各参数均较治疗前明显升高。药物相关的不良反应无明显增加。结论对老年患者,美托洛尔降低心率和血压的同时,明显改善HRV及心功能。     

The selectivity of beta-adrenoceptor antagonists on isoprenaline-induced changes in heart rate, blood pressure, soleus muscle contractility and airways function in anaesthetized cats

The beta-adrenoceptor antagonist of propranolol, metoprolol, atenolol and butoxamine in anaesthetized cats has been measured and compared with the activity of four synthetic phenylethanolamine derivatives. The effects of isoprenaline on four parameters in the anaesthetized cat: heart rate, blood pressure, soleus muscle contractility and airway reactance, were measured and the modification of the isoprenaline dose-response relation by each of the antagonist drugs assessed. Parallel shifts in log dose-response curves for isoprenaline were caused by propranolol for all parameters, by metoprolol and atenolol for each parameter except blood pressure, and butoxamine for each except soleus muscle and heart rate. Selectivity of action of the antagonists between different organs was measured by comparing DR10 values, computed from isoprenaline dose-ratios. Propranolol was the most potent antagonist and showed slight selectivity of action on soleus muscle compared with heart. Atenolol and metoprolol were approximately equipotent and were cardioselective at low doses only. Butoxamine was the least potent antagonist and possessed non-beta-adrenoceptor effects on the parameters measured. Each of the new compounds, 4'-bromo-2'-methoxy-N-isopropyl phenylethanolamine, the 4'-chloro- and 4'-methyl analogues, and 4'-methoxy-N-t-butyl phenylethanolamine, was a potent antagonist but did not exhibit any selectivity of action. The results suggest no clear separation of beta-adrenoceptors into beta 1- and beta 2-subclasses in organs of the cat. There is no apparent separation of beta-adrenoceptor-mediated effects on skeletal muscle and airways.     

In vitro and in vivo effects of SCA40 on guinea pig airways

SCA40 (6-bromo-8-methylaminoimidazo[1,2-a]- pyrazine-2-carbonitrile), a compound which had been described as an opener of Ca²⁺-dependent large conductance potassium channels (BK_Ca channels), was investigated in comparison with salbutamol for in vitro and in vivo bronchospasmolytic effects and for the ability to reverse airways hyperreactivity in guinea pigs. SCA40 reduced the spontaneous tone of isolated guinea pig tracheal rings with a biphasic concentration-response curve (first phase: pD₂ = 8.0, E_Max = 29.7% of maximal effect; second phase: pD₂ = 6.4, E_Max = 72.6%). The salbutamol curve was monophasic (pD₂ = 8.0, E_Max = 100%). Total lung resistance (R_L) was determined in anaesthetized, ventilated guinea pigs. Bronchoconstriction, measured as an increase in R_L, was elicited in normoreactive animals by i.v. infusion of bombesin (100 ng/kg/min) or by i.v. injection of histamine (1.8–5.6 μg/kg). Airways hyperreactivity was induced by acute i.v. administration of pre-formed immune complexes. Intravenous bolus injections of histamine (2.4 μg/kg) were used to define the sensitivity of the airways prior to and after the exposure to immune complex. Following intratracheal (i.t.) administration, SCA40 reversed bombesin-induced bronchoconstriction with an ED₅₀ of 43 μg/kg (E_Max = 57%). The ED₅₀ for salbutamol was 0.8 μg/kg i.t. (E_Max = 78%). Histamine-induced bronchoconstriction in hyperreactive guinea pigs was inhibited by SCA40 with an ED₅₀ of 13 μg/kg i.t. (E_Max = 82%). Salbutamol completely inhibited histamine-induced bronchospasm with an ED₅₀ of 9 ng/kg i.t. In normoreactive guinea pigs, SCA40 prevented histamine-induced bronchoconstriction with an ED₅₀ of 100 μg/kg i.t.; for salbutamol the ED₅₀ in this test was 0.48 μg/kg i.t. Thus, for both SCA40 and salbutamol, the effects obtained at low doses in hyperreactive guinea pigs represent a true reversal of airways hyperreactivity, whereas at higher doses, anti-hyperreactive and bronchospasmolytic properties may account for the observed effects. In conclusion, SCA40 relaxes guinea pig airways smooth muscle in vitro and in vivo, and it partly reverses airways hyperreactivity. With respect to both potency and efficacy, SCA40 is markedly less active than the β-adrenoceptor agonist salbutamol. Received: 23 August 1996 / Accepted: 11 October 1996     

急性心肌梗死患者心律震荡的研究

目的　研究新的心电学指标——心律震荡 (heart rate turbulence,HRT)在急性心肌梗死 (AMI)患者中的变化 ,并与传统指标——心率变异性 (HRV)进行比较 ,分析二者的相关性。方法　选择 5 0名 AMI患者和 5 0例对照者行 2 4 h动态心电图 (Holter)检查 ,计算 HRT的两个参数震荡初始 (TO)和震荡斜率 (TS) ,并对TO、TS与 HRV进行对比分析。结果　 AMI组 TS明显减弱 ,与对照组比较差异有显著性 (P<0 .0 1) ;而 TO在AMI组和对照组差异无显著性 (P>0 .0 5 ) ;TO、TS和 HRV无明显相关性 (P>0 .0 5 )。结论　 AMI组患者 TS减低 ,HRT减弱 ,HRT可能成为评价急性心肌梗死患者自主神经功能状态、预测恶性心律失常和心源性猝死独立的新指标     

美托洛尔控制不停跳冠状动脉搭桥术中心率的临床研究

目的探讨美托洛尔控制冠状动脉搭桥术中心率的效果及安全性。方法回顾性分析4｜D例不停跳冠状动脉搭桥术患者的临床资料。结果40例患者静脉注射美托洛尔1min后HR开始减慢,3min后即显著下降至（69．2±10．8）~／min,与治疗前[（85．1-i-13．5）次／min]差异有统计学意义（t=3．94,P〈0．01）,10min时降到最低值（63．0±6．2）次／min,30min后缓慢上升,但仍未超过治疗前水平;术中平均动脉压相对稳定,治疗后3min、5min、10min、30min与治疗前差异无统计学意义（F=0．56,P〉0．05）。结论美托洛尔能有效控制不停跳冠状动脉搭桥术中心率变化,且不会导致血流动力学变化。     

丙泊酚复合异氟醚对老年人HRV的影响

目的 观察不同靶浓度的丙泊酚复合异氟醚对腹部手术老年患者心率变异性(HRV)的影响.方法 择期手术老年病人45例,随机分成经靶控输注系统(TCI)丙泊酚1μg/ml(Ⅰ组)、2μg/ml(Ⅱ组)和3μg/ml(Ⅲ组)三组,均复合异氟醚吸入.观察人室后麻醉前(TO)、气管插管后即刻(T1)、切皮时(T2)、切皮后15 min(T3)、腹腔探查时(T4)各时段心率(HR)、平均动脉压(MAP)、HRV、异氟醚肺泡呼气末浓度的变化.结果 Ⅲ组T1、T2、T3、T4时总功率(TP)、低频百分率(LFR),T2、T4时高频百分率(HFR)及T4时LF/HF比值均比T0明显下降(P＜0.05或P＜0.01).Ⅲ组T1时TP、LFR、LF/HF均明显低于Ⅰ组(P＜0.01);T2、T3、T4时LF/HF均明显低于Ⅰ组、Ⅱ组(P＜0.05或P＜0.01);T2、T3时TP明显低于Ⅰ组、Ⅱ组(P＜0.01或P(0.05).Ⅲ组、Ⅱ组麻醉期问循环比Ⅰ组稳定,MAP、HR均略低于麻醉前;Ⅰ组T1时MAP、HR均明显高于麻醉前(P＜0.05).结论 持续输注靶浓度为2,μg/ml丙泊酚复合异氟醚可维持老年病人植物神经系统功能均衡性.     

正常人心率减速力和心率变异性的变化及相关性

目的 测定不同年龄正常人心率减速力与心率变异性并分析其相关性,探讨其临床意义。方法 选取正常人90例,根据年龄将受试者分为青年组和老年组,进行24h动态心电图检查,离线计算DC、HRV时域指标及相关系数。结果 老年组DC和HRV值与青年组比较均降低,差异有统计学意义(P<0.05),且DC和HRV显著相关。结论 DC和HRV时域指标随着年龄的增加而减小,这些无创指标可以反映自主神经功能。     

胺碘酮对冠心病心律失常心率变异性的影响

目的观察胺碘酮对冠心病的临床治疗作用,分析该药对心律失常心率变异性的影响。方法收取2009年5月至2010年10月本院治疗的80例冠心病心率失常患者,按照随机原则分为治疗组(40例)和对照组(40例),对照组采用常规扩张冠状动脉和抗心律失常药物,而实验组则每周递减给予胺碘酮治疗。比较两组患者的治疗有效率及相关指标,探讨胺碘酮治疗冠心病心律失常的疗效。结果治疗组的治疗有效率为80%,高于对照组的65%,两组相比具有明显统计学差异(P<0.01)。两组患者在治疗过程中未发生心功能减低、肝功能异常、间质性肺炎、甲状腺功能异常及神经、眼角膜等不良反应。结论胺碘酮对冠心病心律失常的患者疗效明显,价格低廉,用药途径方便、安全,值得临床推广和应用。     

Effects of triazolam on heart rate level and on phasic cardiac response to noise during sleep

The influence of triazolam on cardiac and respiratory activity of healthy male subjects was examined during nights disturbed by airplane noises and during undisturbed nights. Twenty-four subjects, divided into three groups of eight, slept in the laboratory for 7 nights (N0–N6). Following a double blind design, group A (control group) received a placebo every night. Group B received 0.25 mg triazolam and group C received 0.5 mg on nights N3, N4 and N5. On the other nights, they received a placebo. For all three groups, the nights N0, N3 and N5 were disturbed by 32 semi-randomly distributed airplane noises. Air and wall temperatures (20° C) and air humidity (10° C, 52%) were kept constant. Sleep measures, heart rate and respiratory rate were continuously recorded. Results showed that the largest dose of hypnotic drug produced an increase in tonic heart rate in the first part of each night throughout the treatment period (N3, N4, N5). When compared to baseline disturbed night N0, the phasic cardiac response to the noises was significantly attenuated on only the 1st treatment night (N3). Triazolam had no significant effect on nocturnal respiratory rate. No after-effects of the drug were observed for cardiac and respiratory activity on the withdrawal night (N6). The results suggest that, with regard to the drug action, there was either an increase in arousal threshold or a dissociation between long-lasting and short-lasting modifications of heart rate. Contrary to the single night attenuation of phasic cardiac responses, there was no drug tolerance for the hypnotic-related increase in tonic heart rate.