Modification of the Cardiotoxic Effects of Ouabain by Acepromazine, Tetrodotoxin and Magnesium Sulphate

Abstract

Acepromazine (500 μg), tetrodotoxin (0.5 μg) and magnesium sulphate (7.5 mg twice) given intracerebroventricularly increased the doses of ouabain given by continuous intravenous infusion, required to induce arrhythmias and death. Acepromazine (150 μg kg^–1) was also effective when administered intravenously. Acepromazine (1.5 mg kg^–1) and tetrodotoxin (4-6μg kg^–1) given intravenously did not protect against, and even increased, the toxicity of ouabain. Both substances decreased blood pressure and increased heart rate. Tetrodotoxin, but neither acepromazine nor magnesium sulphate given intracerebroventricularly, induced a decrease in the heart rate before ouabain infusion. Acepromazine (500 μg) and tetrodotoxin (0.5 μg), but not magnesium sulphate, given intracerebroventricularly, decreased the blood pressure before ouabain infusion. The results are discussed in relation to the effects of those substances and ouabain on the circulation, and to the fact that the cardiac arrhythmias induced by high doses of ouabain and the protection obtained with tetrodotoxin and magnesium sulphate are, at least in part, mediated by the central nervous system.

Effects of ouabain on carotid body chemoreceptor activity in the cat.

“…The doses of ouabain required to cause maximal chemoreceptor discharge are shown in Table 1. Comparing these doses with those needed to cause ventricular extrasystoles when administered by the intracarotid route (64 + 5 jug/kg, n = 3) or intravenously (69 ± 2,ug/kg, n = 6: Peres-Gomes & Ribeiro, 1979) showed that with intracarotid ouabain a significant difference (P < 0 05) exists between chemoreceptor activation and cardiotoxic doses, whereas little or no difference is apparent between chemoreceptor activation and cardiotoxic effect when ouabain is administered intravenously.…”

A review of chemical defense in harlequin toads (Bufonidae: Atelopus)

“…The interaction between these membrane proteins could have consequences for the function of Atelopus toxin cocktails. Interestingly, tetrodotoxin reduces the toxicity of cardiac glycosides (CGs) when injected directly into the brain of cats but potentiates CG toxicity when given intravenously ( Peres-Gomes and Ribeiro, 1979 ). The difference in effect between TTX administered to the brain and TTX administered intravenously is probably a consequence of the impermeability of the blood-brain barrier to TTX ( Zimmer, 2010 ).…”