Inhibition of sympathetic neuronal transport and ouabain-induced cardiac arrhythmias.
The objective of the present investigation was to determine whether a correlation exists between the effect of ouabain to inhibit activity of the sympathetic neuronal transport system and the effect of the drug to produce cardiac arrhythmias. 3H-d,1-Metaraminol was used to monitor activity of the transport system in intact animals as well as in isolated perfused hearts. Accumulation by myocardial tissue (LV; RV), spleen (S), and gastrocnemius muscle (GM) of the guinea pig was not altered by the lowest dose of ouabain, 100 microgram/kg. A subarrhythmic dose, 150 microgram/kg, as well as the arrhythmic dose of ouabain, 212+/-24 microgram/kg, decreased accumulation by LV, RV, and S. Several different concentrations of ouabain were studied in the isolated perfused guinea pig heart preparation. Only the highest concentration, 5 X 10(-6)M was capable of decreasing accumulation of metaraminol. However, all but the lowest concentration of ouabain produced toxic arrhythmias. Thus, neither in intact animals nor in isolated perfused hearts could the dose of ouabain required to inhibit the sympathetic neuronal transport system be correlated with the dose of ouabain required to produce cardiac arrhythmias. It is concluded that ouabain inhibition of the sympathetic neuronal transport system does not play a role in the genesis of ouabain-induced cardiac arrhythmias.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008680:Metaraminol / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D010042:Ouabain; D008680:Metaraminol