毛冬青不同提取部位扩血管作用及对蛙心的影响

目的 研究毛冬青不同提取部位的扩血管作用及对蛙心的影响.方法 依次用石油醚、乙酸乙酯、正丁醇和水提取毛冬青,得到不同极性提取物,分别观察其对去内皮兔胸主动脉环的扩张作用.根据结果,选择作用显著的提取物再进一步观察其对NE预收缩的去内皮动脉环的影响及其对正常蛙心和心衰模型的影响.结果 毛冬青的石油醚部位(PEI)、乙酸乙酯部位(EAI)、水相部位(AEI)、总提取物(TEI)对正常去内皮动脉环几乎无作用,正丁醇提取物(NAI)对兔去动脉环的静息张力有微弱的作用,显示出扩张的趋势.不同剂量的正丁醇部位可使NE预收缩动脉环产生明显的舒张作用,对正常离体蛙心的心肌收缩力有明显的增强作用,对低钙造成的心衰没有明显的作用.结论 毛冬青正丁醇提取部位(NAI)具有一定的扩血管作用、增强心肌收缩力的作用.正丁醇部位是其主要的有效部位.     

Cardiac effects of R 79595 and its isomers (R 80122 and R 80123) in an acute heart failure model

Summary R 79595 (N-cyclohexyl-N-methyl-2-[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1-b]-quinazolin-7-yl) methylene] amin] oxy] acetamide) and its isomers represent a novel class of compounds with phosphodiesterase (PDE) inhibitory and cardiotonic (positive inotropic) actions. The cardiac effects of this class of compounds were investigated in the hexobarbital-depressed heart-lung preparation of the guinea-pig.After induction of heart failure (reduction of cardiac output to 25% of the initial value) cumulative addition of R 79595 or its isomers R 80122 (E-isomer) and R 80123 (Z-isomer) concentration-dependently reversed the cardiac depressant effects of hexobarbitone-Na. With regard to reconstitution of contractility and cardiac function R 80122 (E-isomer) was 10 fold more potent than R 79595 (1:1 mixture of the isomers) and nearly 100 fold more potent than R 80123 (Z-isomer).Furthermore, the cardiotonic action of the most potent isomer (R 80122) was compared to the effects of several positive inotropic reference compounds. The order of cardiotonic potency was as follows: (–)-adrenaline> R 80122=adibendan>digitoxin>milrinone=enoximone >theophylline. Adibendan (EC₅₀ value: 6.7±1.8×10.^–8 mol/l), which showed cardiotonic effects in the same concentration range as R 80122 (EC₅₀ value: 6.1±1.3×10^–8 mol/l), was significantly (p<0.01) less effective than R 80122 with respect to the maximally induceable increase in cardiac output (CO).The cardiotonic effects of R 80122 could be observed in the low concentration range of 3×10^–8 to 1×10^–6 mol/l, whereas enoximone (EC₅₀ value: 1.2±0.1×10^–5 mol/l) and milrinone (EC₅₀ value: 8.9±3.5×10^–6 mol/l) elicited positive inotropic effects at 100 fold higher concentrations.Digitoxin was 10 fold less and theophylline was 300 fold less potent than R 80122 with regard to reconstitution of heart function. The cardiotonic effects of R 80122 were not accompanied by an increase in heart rate as found with milrinone, theophylline or (–)-adrenaline in this model.Furthermore, the PDE inhibitory effect of R 79595 and its E-isomer R 80122 were investigated in partially purified isoenzymes from guinea-pig ventricles. The IC₅₀ values of R 79595 and R 80122 on PDE I–IV were compared to the IC₅₀ values of adibendan, milrinone, enoximone and theophylline. The selectivity of an inhibitor for PDE III was evaluated by division of its IC₅₀ values on PDE I, II and IV by the IC₅₀ value on PDE III. R 80122 was the most potent and selective PDE III inhibitor. The IC₅₀ value was 0.017±0.001 µmol/l. IC₅₀ ratios ranged from 2353 (PDE II/PDE III) to 7000 (PDE I/PDE III). The PDE IV/PDE III ratio for R 80122 (5118) was more than 10 times higher than the PDE IV/PDE III ratio calculated for adibendan (333) which displayed the highest PDE III selectivy and potency (IC₅₀ 0.36±0.04 µmol/l). among the reference compounds. Milrinone and enoximone also preferentially inhibited PDE III, whereas theophylline inhibited all four isoenzymes in an unselective manner with low potency.Since the EC₅₀ values of R 80122 for cardiotonic effects and the IC₅₀ value for PDE III inhibition were of the same order of magnitude, it can be assumed that potent and selective PDE III inhibition may be in part responsible for the cardiotonic effects of R 80122 observed in the acute heart failure model.The potent cardiotonic properties and the absence of positive chronotropy revealed by this study suggest that R 80122 might exert a beneficial effect in the treatment of acute heart failure. Correspondence to J. Schneider at the above address     

Biochemical basis for the low sensitivity of the rat heart to digitalis

Summary The concentration of cardiac glycosides to produce positive inotropic effects in the rat heart is markedly higher than that in other species. Such a low digitalis sensitivity of the rat heat is attributed to the low affinity of cardiac Na⁺, K⁺-ATPase for digitalis in this species. In the present study the biochemical cause which is responsible for the formation of the unstable complex between the glycosides and Na⁺, K⁺-ATPase or positive inotropic, receptor in the rat heart was examined using Na⁺, K⁺-ATPase preparations obtained from rat hearts, guinea-pig hearts and rat brains as well as isolated, electrically stimulated atrial preparations obtained from these animals. Monensin, which alters transmembrane Na⁺ movements without interacting with the cardiotonic sites on Na⁺, K⁺-ATPase, had equivalent potencies in guinea-pig and rat hearts. Cassaine, which lacks a lactone ring but interacts with cardiotonic sites on Na⁺, K⁺-ATPase, increased the force of contraction in guinea-pig hearts at low, but in rat hearts only at high, concentrations. AY-22,241 (Actodigin) and prednisolone-3,20-bisguanylhydrazone (PBGH) bind to cardiotonic sites on Na⁺, K⁺-ATPase and had a similar spectrum as cassaine in these two species. Actodigin has an altered lactone ring resulting in a marked reduction of the inotropic potency, and PBGH is devoid of this structure. With the latter agent, the rabbit was as insensitive as the rat, although both rabbit and guinea-pig are equally sensitive to digitalis. K⁺ delayed the development of the positive inotropic action of ouabain with a minimal effect on the plateau response in guinea-pig hearts. In rat hearts, however, K⁺ markedly lowered the plateau response without affecting the time course of the response. These results indicate that the low sensitivity of the rat heart to digitalis is due to a difference in the glycoside binding sites on Na⁺, K⁺-ATPase; but the difference cannot be explained by the lack of a lactone ring complementary binding sites. The difference seems to result from the absence of lipid barrier which regulates the rate of release of cardiac glycosides from their binding sites on Na⁺, K⁺-ATPase.This work was supported by U.S. Public Health Service grant, HL-16052 and by the Michigan Heart Association     

丹参对慢性肝炎的抗纤维化治疗

目的观察丹参对慢性肝炎纤维化指标的疗效.方法应用复方丹参治疗,分别选择20例慢性乙型肝炎,设置治疗组与对照组,对肝功能及血清纤维化指标进行对比.结果治疗组肝纤维化指标治疗后显著低于治疗前水平,治疗组疗效显著优于对照组,疗程中未发现毒副作用.结论复方丹参对改善血清纤维化指标有明显作用.     

强心胶囊治疗慢性心衰450例临床观察

应用自拟强心胶囊治疗慢性心衰４５０例，并与地高辛治疗的５０例作对照。结果表明，强心胶囊组取得较好的疗效，用药后五天即能逐渐撤除地高辛，心衰症状明显缓解，总有效率为９３．６％。，而且对心功能三项指标均有明显改善（ｐ＜０．００１），疗效优于对照组（ｐ＜０．０５）。     

复方丹参滴丸干预阿司匹林抵抗的临床试验

目的探讨复方丹参滴丸对阿司匹林抵抗患者的干预效果。方法采用比浊法测定血小板聚集率,将阿司匹林抵抗及半敏感的患者30例随机分为3组,每组10例:阿司匹林+复方丹参滴丸组;单服复方丹参滴丸组及单服阿司匹林组。干预2周后分别复查血小板聚集率。结果阿司匹林+复方丹参滴丸组和单用复方丹参滴丸组干预后二磷酸腺苷(ADP)诱导的血小板聚集率分别为60.29%和66.33%,较干预前的70.65%和71.72%分别下降了10.36%(P<0.01)和5.39%(P<0.05);而单用阿司匹林组干预后较干预前无统计学差异(P>0.05)。花生四烯酸(AA)诱导的血小板聚集率在阿司匹林+复方丹参滴丸组和单用复方丹参滴丸组干预后分别为12.27%、17.67%,较干预前24.01%、24.37%,分别下降了11.74%(P<0.01)、5.39%(P<0.05)。单用阿司匹林组干预前后无统计学差异(P>0.05)。结论复方丹参滴丸可以增强患者对阿司匹林的敏感性,两药有协同抗血小板作用。     

强心药早期干预婴幼儿肺炎合并心功能不全表现的疗效研究

目的研究强心药早期干预婴幼儿肺炎并发心功能不全表现的疗效。方法32例心功能不全代偿期给强心药为观察组，24例心功能不全失代偿期给强心药为对照组，观察其血气分析结果及强心药使用次数、心功能不全纠正时间。结果心功能不全失代偿期患儿血液PH值、PaO2及SaO2均低于心功能不全代偿期患儿，强心药使用次数多，心功能不全纠正慢。结论重症肺炎在心功能不全代偿期，予以强心药干预，发挥其正性肌力作用，其效果优于发生明显心功能不全失代偿期患儿。     

香加皮中强心苷类对大鼠离体心脏的强心作用比较

目的:比较香加皮中4种强心苷类成分的强心作用并确定其时效和量效关系。方法:采用Langendor-ff离体心脏灌流法,待实验心脏稳定后给予受试药,记录并比较心率(HR)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、dp/dtmax、dp/dtmin、等心功能指标。结果:香加皮中4种强心苷类成分均能提高大鼠离体心脏的心肌收缩力和左心室收缩压,随着各自剂量的逐渐增大,强心作用逐渐增强,到达某一剂量后,强心作用开始降低。与给药前相比,4种强心苷成分在给药后HR、LVSP、dp/dtmax均有显著性的改变(P<0.05)。在时效关系研究中达峰顺序依次为xysmalogenin、杠柳毒苷苷元、杠柳毒苷、强心苷G1。在量效关系研究中杠柳毒苷的最大作用浓度为0.15mg/只,而杠柳毒苷苷元的最大作用浓度为0.30mg/只。结论:4种强心苷类成分都能增强大鼠离体心脏功能,均兼备正性肌力作用和负性频率作用。