马利筋甙的强心作用

从云南产马利筋中分离出强心成分马利筋甙(curassavicin),具有强心甙的各种颜色反应,动物试验证明具有洋地黄样的强心作用。由蛙腿淋巴囊给药,使蛙心特性的停止于收缩状态,按小林芳人法作在位兔心试验;Langendorff法作离体豚鼠心脏灌注及心电图观察,证明马利筋甙对心脏具正性肌力作用,负性频率作用和负性传导作用。与g-毒毛旋花子甙作对照平行试验,二者作用性质很相似,表现为作用迅速而蓄积性很小。马利筋甙的生物学强度比原生药大732倍,而仅为g-毒毛旋花子甙的1/4—1/5。     

国产乙酰毒毛旋花子甙的实验观察

国产乙酰毒毛旋花子甙,具有洋地黄类药物相似的强心作用,而且作用迅速,持续时间短暂,毒性消失快,与哇巴因有累加作用,适合于作“洋地黄耐量试验”。本药对心脏作用明显,实验动物死亡前均曾有严重心律紊乱产生,死亡主要原因与逾量给药有关。并推荐在“洋地黄耐量试验”时,以连续灌注法为佳。     

滇杠柳甙的强心作用

由滇杠柳新鲜茎皮中提出总甙,通过在位蛙心及兔心、兔心电图及离体豚鼠心实脸,证明本品有强心作用,其强心作用特点类似g-毒毛旋花子甙,鴿平均致死量为5.9±1.0毫克/公斤(标准差)。     

强心灵(黄夹甙)

本品是从国产夹竹桃科植物黄花夹竹桃(Thevetia Peruviana Merr.)果仁中制备的一种混合强心甙。主要为黄花夹竹桃次甙甲(Peruvoside,C_(30)H_(44)O_9)、黄花夹竹桃次甙乙(Neriifolin,C_(30)H_(46)O_8)和单乙酰黄花夹竹桃次甙乙(Cerberin,C_(32)H_(48)O_9)三种亲脂性甙。〔作用特点〕本品具有明显的强心作用,作用出现迅速,蓄积作用和副作用较低,注射时与毒毛旋花子甙K相似,口服可代替     

肉毒碱对实验性衰竭心脏功能的影响

肉毒碱carnitine是一广泛存在于组织中的氨基酸,本文报告人工合成d,l-carnitine盐酸盐(VBt)对麻醉猫衰竭心脏及离体豚鼠衰竭心脏功能的影响。用缓慢恒速静注戊巴比妥钠引起猫急性心衰。给心衰猫静注VBt 50 mg/kg/min,共5分钟。给药后,MAP、LVP及LVdp/dt max均明显升高,CVP及LVEDP轻度下降,HR无明显改变。当VBt与毒毛旋花子甙K合用时,能增加后者引起心律失常的剂量和治疗宽度。VBt对正常离体豚鼠心脏除引起HR减慢外,对心收缩力和冠脉血流量均无明显影响。当用乏氧灌流引起急性心衰时,VBt则加强心收缩力和增加冠脉血流,并推迟心衰的发展。此外VBt还能使大鼠心肌组织耗氧量明显降低。     

夹竹桃乙素的药理性质及与g-毒毛旋花子甙、異羟基洋地黄毒甙、洋地黄毒甙的比较研究

夹竹桃乙素是夹竹桃叶中所含的主要强心成分.本文证明其药理性质不同于g-毒毛旋花子甙和洋地黄毒甙,而与异羟基洋地黄毒甙(digoxin)相近.具有较小的蓄积作用和较大的口服吸收率,以及较强的生物活性.作者认为临床上可用以代异羟基洋地黄毒甙使用.     

夹竹桃乙素的药理性质及与g-毒毛旋花子甙、異羟基洋地黄毒甙、洋地黄毒甙的比较研究

夹竹桃乙素是夹竹桃叶中所含的主要强心成分.本文证明其药理性质不同于g-毒毛旋花子甙和洋地黄毒甙,而与异羟基洋地黄毒甙(digoxin)相近.具有较小的蓄积作用和较大的口服吸收率,以及较强的生物活性.作者认为临床上可用以代异羟基洋地黄毒甙使用.     

羊角拗强心甙与g-毒毛旋花子甙的效价比较

在同样条件下比较了羊角拗强心甙和g-毒毛旋花子甙的毒性、治疗指数、安全界、破坏速度,发现羊角拗强心甙的毒性比g-毒毛旋花子甙约小1/2左右.在治疗指数及安全界上,羊角拗强心甙虽然比g-毒毛旋花子甙略窄些;但从临床角度上看,其治疗剂量的宽度(有效剂量和中毒剂量的间距)在羊角拗强心甙却比g-毒毛旋花子甙为宽.这也正是羊角拗强心甙比g-毒毛旋花子甙优越之处.在用相应的剂量下(1/3,1/2,2/3 LD₅₀),二药在减慢心率的作用上,虽然略有参差不齐,但总的趋势是一致的。在引起心脏的传导阻滞、室性心动过速上,二药之间看不出明显差别.在体内破坏速度上,羊角拗强心甙略慢些.     

黄花夹竹桃强心甙的药理研究 Ⅱ.Neriifolin的药理

上述实验证明从云南产黄花夹竹桃种仁中提得的 neriifolin 具有强心作用,并具有较高的生物活性,其效价大于洋地黄毒甙和异羟基洋地黄毒甙,但小于 g—毒毛旋花子甙;此外,neriifolin 具有一定蓄积作用,但比洋地黄毒甙为小,豚鼠体试验经口投药可部份被吸收。     

羊角拗甙的藥理与臨床应用(文献综述)

毒毛旋花子甙K为冶疗心力衰竭的药物之一。毒毛旋花子产于热带非洲地区,在国内寻求国产原料或其代用品,实属必要。近几年来国内对代用品羊角拗的药理学研究及临床应用均获得一定成果。兹综述文献如下: 羊角拗及其成份羊角拗为夹竹桃科(Apocynaceae)植物Strophanthus divaricatus(Lour)Hook et Arn,药用部份为毒性种子。 1940年朱任宏氏首先从我国广东省兴宁县山地中之羊角拗种子中提得白色无晶型碱皂体,含量为1.8％,经加酸分解得三种结晶性配基称为羊角拗皂草水解素甲、乙、丙(Strophanthiline A.B.C.)     

黄麻甲甙,哇巴因和康毗丁在豚鼠及猫心肺制备上强心作用的比较研究

本文报告强心药黄麻甲甙的治疗作用强度、治疗宽度并与已知强心药作比较性研究。在豚鼠、猫心肺制备上,以戊巴比妥钠引起心力衰竭(少数自发性心力衰竭),分别测定了黄麻甲甙、哇巴因、康毗丁的治疗作用及治疗宽度,以输出量或静脉压的改善作为、“治疗量”的指标;以静脉压重又上升,波幅加大,心律不齐作为“中毒量”指标;以发生心室纤维颤动作为“致死量”指标;计算了三种药物的治疗量/致死量、中毒量/致死量的百分率,黄麻甲甙在二种心肺制备上,对心力衰竭有良好的治疗作用,其治疗量在猫身上小于哇巴因;在豚鼠身上则与哇巴因相近,不仅作用较强,而且作用较其他二种已知强心甙发生得更早。在治疗量/致死量的百分率方面,在豚鼠心肺制备上,黄麻甲甙为6.05%、哇巴因17.45%、康毗丁14.41%。在猫心肺制备上则分别为10.86%、21.29%及22.96%;即黄麻甲甙的治疗宽度为上述二种强心甙的2～3倍,在统计学上有显著性差异。在中毒量/致死量的百分率方面,三种强心甙差异不大。本文对豚鼠心肺制备的实验方法及其作为测定强心甙治疗宽度的工具,作了简短的讨论。     

Suppression of positive inotropic and toxic effects of cardiac glycosides by amiloride

Effects of amiloride on the inotropic and toxic actions of cardiac glycosides were examined using left atrial muscle isolated from guinea pig heart. Preincubation of atrial muscle with amiloride significantly decreased the maximum positive inotropic effect of dihydrodigoxin but failed to reduce that of isoproterenol. Amiloride prevented the contracture and significantly reduced the incidence of arrhythmias induced by 2 microM digoxin. Similar experiments examining 5 microM digoxin-induced arrhythmias showed that amiloride increased both the time required to produce arrhythmias and the fractional occupancy of sarcolemmal Na,K-ATPase by digoxin at the onset of arrhythmias. The antagonism of cardiac glycoside actions was best observed during the decline in developed tension elicited by amiloride subsequent to its initial positive inotropic effect. Amiloride had no effect on binding site concentration for ATP-dependent [3H]ouabain binding but decreased affinity of the binding sites for ouabain in membrane preparations obtained from guinea pig heart. Furthermore, amiloride inhibited Na,K-ATPase activity and increased the IC50 value for ouabain inhibition of the enzyme. These results indicate that amiloride antagonizes the positive inotropic and toxic effects of cardiac glycosides. Possible mechanisms for the antagonism include inhibition of sarcolemmal Na+/Ca2+ or Na+/H+ exchange.     

Lack of interaction of spironolactone with ouabain guinea pig isolated heart muscle preparations.

The effect of spironolactone on ouabain action was studied in experiments on guinea pig isolated heart muscle preparations. There was no effect of spironolactone on the ouabain-induced positive inotropic or toxic effects in isolated papillary muscles. This was accompanied by a lack of spironolactone effect on myocardial ouabain uptake. Only rather high spironolactone concentrations (1 X 10(-4) M) led to a reduced cardiac ouabain uptake (about 10%). The subcellular distribution pattern of ouabain, however, remained unchanged under these conditions. Studies on ouabain binding to a cardiac NaK-ATPase supported the conclusion that a direct interaction of spironolactone and cardiac glycosides at the myocardium could be ruled out.     

Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohli: Forskolin

Forskolin is a diterpene derivative isolated from the Indian plant Coleus forskohli. Forskolin has positive inotropic action on the isolated guinea pig heart, on the isolated left atrium of the guinea pig heart and on the dog and cat heart in situ. It increases the heart rate. The positive inotropic effect on the increase of heart rate are not blocked by beta-blockers. On reserpinized dogs the actions on the heart could also be seen. With high doses the action potential of the guinea pig papillary muscle is shortened. The positive inotropic effect could be differentiated from the effects of theophylline, cardiac glycosides and veratrine. Forskolin lowers the blood pressure in dogs and cats and also in spontaneously hypertensive and renal hypertensive rats.     

Positive inotropic effect of ouabain on isolated heart is accompanied by activation of signal pathways that link Na+/K+-ATPase to ERK1/2

Exposure of cultured rat cardiac myocytes to ouabain is known to cause the interaction of Na+/K+-ATPase with adjacent proteins, leading to activation of multiple signal transduction pathways, regulation of growth-related genes, and hypertrophy. The aim of this work was to determine if the proximal signaling events identified in cultured myocytes also occur in isolated intact hearts of rat and guinea pig in response to positive inotropic doses of ouabain. Langendorff rat heart preparations were exposed to 50 microM ouabain to produce positive inotropy without toxicity, and assayed for Src kinase, protein kinase C, and extracellular signal-regulated kinases 1 and 2 (ERK(1/2)). These kinases were rapidly activated by ouabain as in cultured cells. In isolated guinea pig hearts, 1 microM ouabain caused ERK(1/2) activation comparable to the effect of 50 microM ouabain in rat heart and consistent with the higher ouabain sensitivity of the contractility of guinea pig heart. These data show that the proximal ouabain-induced signal pathways previously noted in cultured cells are not artifacts of dispersion/culturing of myocytes, and are not the peculiar properties of the rat heart with its relatively low ouabain sensitivity. They also suggest that treatment with positive inotropic doses of cardiac glycosides is likely to be associated with changes in the cardiac phenotype.     

心甙neriifolin对红细胞钾离子转运的影响及其与动物致死作用的关系

以冷藏又经温育的人血,观察neriifolin对红细胞钾离子转运的影响及其与动物致死作用的关系,以哇巴因(ouabain)和地吉妥辛(digitoxin)作对照,比较三种心甙阻抑钾内流的作用和对豚鼠的致死作用.发现这两种作用都以哇巴因为最强,neriifolin次之,地吉妥辛最弱,两种作用强度的顺序是相符的.结合文献讨论了相符的理论根据.本文提出,是否可以将心甙阻抑红细胞钾内流的作用作为心甙生物活性的另一指标.     

乙酰肉毒碱和肉毒碱抗乏氧性心衰及其与强心甙合用的对比研究

Experiments on Langendorff's guinea pig heart showed that, when 0.1M acart (acetylcarnitine) or cart (carnitine) was given at 1 ml/min for 5 min, both prevented heart failure from hypoxia. The beneficial effects of acart were more powerful than those of cart.In isolated rabbit right atria, when acart or cart (0.05 ml of 0.04 M) was followed by strophanthin K (3.75 μg), acart+strophanthin K increased significantly contraction amplitude, but cart+strophanthin K didnot. Acart or cart (0.1 ml of 0.04 M)were found to significantly shorten the duration of rhythm disorder-induced by strophanthin K (50 μg). The duration of rhythm-disorder in the former (1.17±0.44 min) was significantly shorter than that in the latter (2.67±0.33 min).LD₅₀ of acart and cart in mice were 1228 mg/kg and 974 mg/kg, respectively.It is concluded that acart was more effective and less toxic than cart in the treatment of heart failure.     

鬚瓣开口箭的药理研究Ⅰ.强心作用与生物活性测定

从百合科鬚瓣开口箭的根茎分得开口箭素。呈强心甙顏色化学反应。由蛙腿淋巴囊給药,能使蛙心停止于收縮期。在位兔心試驗,靜脉注射1.2毫克/公斤后增大心动振幅,继而呈現心收縮不規则,30分钟后使心跳停止。按Langendorff法制备离体兔及豚鼠心脏,用1:10⁵溶液灌注,初期振幅增大,继而节律不整,20—30分钟后心脏停止于收縮或舒张状态。对猫及脉鼠均产生典型的洋地黄样心电图改变:使P—R,R—R间期延长、T波压低或倒置。按照中国药典規定測定其鸽的最小致死量为:1.394±0.069毫克/公斤。其生物活性大于黄花夹竹桃甙(thevetin),而小于g-毒毛旋花子甙。     

Über Acetyl-Cardenolide aus Thevetia peruviana

Acetyl Cardenolides from Thevetia peruviana From the fermented seeds of Thevetia peruviana we isolated a neriifolin monoacetate (= cerberin) and a peruvoside monoacetate in addition to the already known principal glycosides neriifolin and peruvoside. - The NMR spectra demonstrate both glycosides to be esterified at C-2 of the L-thevetose. These acetyl glycosides could not be detected in the unfermented drug; instead, we isolated acetylthevetin B, the corresponding primary glycoside of cerberin. - Partial acetylation of neriifolin yields cerberin and the isomeric neriifolin-4'-monoacetate.