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.