IN-VIVO EFFECTS OF A NOVEL CALCIUM-ANTAGONIST (R56865) AGAINST INDUCED EPOXYSCILLIROSIDIN AND TULP POISONING IN SHEEP

Two anaesthetized sheep were intoxicated with epoxyscillirosidin, the main cardio-active bufadienolide, extracted from Homeria pallida (Nata l yellow tulp). The epoxyscillirosidin was injected intravenously as a bolus of 50 mu g/kg, followed 30 min later by a continuous infusion i n a normal saline drip (0,9% Nacl) at 25 mu g/kg/h. In addition, anoth er two conscious sheep were poisoned by intraruminal dosing of 1,25 g/ kg of dried H. pallida plant material. Electrocardiograms, heart and r espiratory rates and venous-acid-base levels were recorded prior to an d at approximately 30-60 min intervals during the course of the experi ment. Additional recordings were made when animals showed signs of int oxication. R56865 (Janssen Pharmaceutica, Pty Ltd), a novel Ca++ antag onist, was administered at the first distinct signs of cardiac disturb ances in the sheep given epoxyscillirosidin and after development of t achycardia and dyspnoea in those that received plant material. Activat ed charcoal was drenched at 3 g/kg to both sheep that received H. pall ida about 1 h after the initial administration of R56865. All H. palli da sheep and one of the epoxyscillirosidin sheep survived. The signs o f 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 transi ent improvement in conduction disturbance was recorded, the animal die d 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 simila r cardiac disturbances in vitro. The potential use of R56865 together with activated charcoal is discussed.