Swan G E, Schultz R A, Kellerman T S, Mülders M S, Maartens B P, Van der Walt J J
Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.
Onderstepoort J Vet Res. 1995 Sep;62(3):163-6.
Two anaesthetized sheep were intoxicated with epoxyscillirosidin, the main cardio-active bufadienolide, extracted from Homeria pallida (Natal yellow tulp). The epoxyscillirosidin was injected intravenously as a bolus of 50 micrograms/kg, followed 30 min later by a continuous infusion in a normal saline drip (0.9% NaCl) at 25 micrograms/kg/h. In addition, another two conscious sheep were poisoned by intraruminal dosing of 1,25 g/kg of dried H. pallida plant material. Electrocardiograms, heart and respiratory rates and venous-acid-base levels were recorded prior to and at approximately 30-60 min intervals during the course of the experiment. Additional recordings were made when animals showed signs of intoxication. R56865 (Janssen Pharmaceutica, Pty Ltd), a novel Ca++ antagonist, was administered at the first distinct signs of cardiac disturbances in the sheep given epoxyscillirosidin and after development of tachycardia and dyspnoea in those that received plant material. Activated charcoal was drenched at 3 g/kg to both sheep that received H. pallida about 1 h after the initial administration of R56865. All H. pallida sheep and one of the epoxyscillirosidin sheep survived. The signs of intoxication with H. pallida, namely groaning and tachypnoea, abated within minutes of treatment with R56865, but returned c. 30 min later in both animals. The treatment apparently had little effect on heart rate and EKG changes. One of the epoxyscillirosidin sheep was treated while exhibiting paroxysmal ventricular tachycardia. Although a transient improvement in conduction disturbance was recorded, the animal died soon afterwards. The results of this study indicate that the in vivo response of R56865 against induced bufadienolide cardiac disturbance in sheep is not as evident as that observed with R56865 against similar cardiac disturbance in vitro. The potential use of R56865 together with activated charcoal is discussed.
选取两只麻醉的绵羊，用从苍白荷马（纳塔尔黄郁金香）中提取的主要具有心脏活性的蟾蜍二烯羟酸内酯环氧西利罗苷使其中毒。环氧西利罗苷以50微克/千克的剂量静脉推注，30分钟后，以25微克/千克/小时的速度在生理盐水滴注（0.9%氯化钠）中持续输注。此外，另外两只清醒的绵羊通过瘤胃内给药1.25克/千克的干燥苍白荷马植物材料而中毒。在实验过程中，在给药前以及大约每隔30 - 60分钟记录心电图、心率、呼吸频率和静脉酸碱水平。当动物出现中毒迹象时进行额外记录。在静脉注射环氧西利罗苷的绵羊出现最初明显的心脏紊乱迹象时，以及在接受植物材料的绵羊出现心动过速和呼吸困难后，给予新型钙离子拮抗剂R56865（杨森制药有限公司）。在最初给予R56865约1小时后，给两只接受苍白荷马的绵羊灌服3克/千克的活性炭。所有接受苍白荷马的绵羊和一只接受环氧西利罗苷的绵羊存活下来。接受苍白荷马中毒的绵羊出现的中毒迹象，即呻吟和呼吸急促，在用R56865治疗后几分钟内减轻，但约30分钟后在两只动物中又恢复。该治疗对心率和心电图变化显然影响不大。其中一只接受环氧西利罗苷的绵羊在出现阵发性室性心动过速时接受治疗。尽管记录到传导紊乱有短暂改善，但该动物随后不久死亡。本研究结果表明，R56865在体内对绵羊诱导的蟾蜍二烯羟酸内酯心脏紊乱的反应不如其在体外对类似心脏紊乱的反应明显。讨论了R56865与活性炭联合使用的潜在用途。
