Modification of the cardiotoxic effects of ouabain by acepromazine, tetrodotoxin and magnesium sulphate.

Acepromazine (500 microgram), tetrodotoxin (0.5 microgram) and magnesium sulfate (7.5 mg twice) given intracerebroventricularly increased the doses of ouabain given by continuous intravenous infusion, required to induce arrhythmias and death. Acepromazine (150 microgram kg-1) was also effective when administered intravenously. Acepromazine (1.5 mg kg-1) and tetrodotoxin (4-6 microgram 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 microgram) and tetrodotoxin (0.5 microgram), 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.