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EFFECTS OF YEW ALKALOIDS AND RELATED COMPOUNDS ON GUINEA-PIG ISOLATED PERFUSED HEART AND PAPILLARY MUSCLE

机译:紫杉碱和相关化合物对几内亚猪隔离的灌注的心和乳头肌的影响

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The mechanical and electrical effects of selected yew alkaloids were studied on two different cardiac preparations: the isolated coronary perfused heart and the isolated papillary muscle of the guinea-pig. In the isolated heart, the Winterstein acid type alkaloids 1, 2 and 3 induced electrical and mechanical effects similar to those reported after yew intoxication (negative inotropic effect, block of atrio-ventricular conduction), but the coronary flow was unchanged. Taxine B (1), the most potent compound of this group, reduced cardiac contractility and the maximum rate of depolarisation of the action potential in the isolated papillary muscle, acting as a class I antiarrhythmic drug. In the isolated heart, the cinnamates 4 and 5, corresponding to the degradation products of 1 and 3, exerted arrhythmogenic effect due to a reduction of coronary flow. No alterations in electrical and contractile activities were in fact recorded after perfusion of the isolated papillary muscle with 4. Taxine A (6) and the taxane alcohol 7, corresponding to the terpenoid core of 3 had no significant cardiac effect. Our results suggest that the poisonous properties of the yew tree are probably due to the combined activity of alkaloids of the Winterstein acid type and their corresponding cinnamates, which can reduce both the excitability and the coronary flow of the heart. [References: 20]
机译:在两种不同的心脏制剂上研究了所选紫杉生物碱的机械和电学效应:离体的冠状动脉灌注心脏和离体的豚鼠乳头肌。在离体心脏中,温特斯坦酸型生物碱1、2和3诱导的电和机械效应类似于紫杉醇中毒后报道的那些(负性肌力作用,房室传导阻滞),但冠状动脉血流没有改变。紫杉烷B(1)是该组中最有效的化合物,可降低心脏收缩力,并在分离的乳头肌中最大程度地消除动作电位的去极化率,可作为I类抗心律不齐药物。在离体心脏中,对应于1和3降解产物的肉桂4和5由于减少了冠状动脉血流而产生了致心律失常作用。实际上,在用4灌注离体乳头肌后,没有记录到电气和收缩活动的改变。紫杉碱A(6)和紫杉烷醇7(对应于3类萜的核心)没有明显的心脏作用。我们的结果表明,紫杉树的毒性性质可能是由于温特斯泰因酸类型的生物碱及其相应的肉桂酸盐的结合活性所致,从而降低了心脏的兴奋性和冠状动脉血流。 [参考:20]

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