Uptake and pharmacological effect of gitoxin and gitaloxin in rat and guinea-pig perfused hearts. Comparison with digitoxin and digoxin.
Rat and guinea-pig hearts were perfused with gitoxin and gitaloxin at various concentrations. Simultaneously, the amplitude of myocardial contractions was recorded. In the case of guinea-pig, digoxin and digitoxin were studied, too. After perfusion, the amount of cardiac glycoside taken up by each heart was determined. The uptakes of gitoxin and gitaloxin by rat hearts were similar and directly proportional to the glycoside concentration in the perfusion medium. In guinea-pig hearts, the sequence in binding amount of digoxin less than gitaloxin less than gitoxin less than or equal to digitoxin. The positive inotropic effects of the four glycosides in guinea-pig hearts were similar; the toxicity, however, increased in the sequence: gitoxin less than gitaloxin congruent to digoxin less than digitoxin. Briefly, gitoxin is bound to the guinea-pig heart muscle much more than its positional isomer, digoxin; though it shows a similar positive inotropic effect on guinea-pig hearts, gitoxin appears to be markedly less toxic than the three other glycosides.
D000818:Animals; D004074:Digitoxin / Q000378:metabolism / Q000494:pharmacology*; D004077:Digoxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
D004077:Digoxin; D004074:Digitoxin; C021029:gitaloxin; C005003:gitoxin