Comparison of the cardiac effects of ASI-222 HCl, an aminosugar cardiac glycoside, and digoxin.
The effects of ASI-222 HCl and digoxin on cardiac contractile force, dP/dt, heart rate and mean blood pressure in the dog were evaluated following i.v. administration. Additional studies were performed on isolated, electrically driven rabbit atria with both ASI-222  and digoxin. Our data show that ASI-222 (40 microgram/kg) in non-vagotomized dogs produced a two-fold greater increase in cardiac contractile force and dP/dt than did an equimolar dose of digoxin. ASI-222 caused a peak increase in contractile force and dP/dt 10 min after administration, whereas the peak to digoxin occurred at 30 min. ASI-222 was more effective in non-vagotomized dogs in increasing contractile force and dP/dt than in vagatonized dogs. The inotropic responses to digoxin were not reduced by vagotomy. Studies on isolated electrically driven rabbit atria indicate ASI-222 to be 7-8 times more potent than digoxin in increasing contractile force. These data demonstrate that ASI-222 produces an earlier and greater increase in contractile force and dP/dt than digoxin in equimolar doses.
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004073:Digitoxigenin / Q000031:analogs & derivatives / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D013997:Time Factors; D014628:Vagotomy
D000617:Aminoglycosides; D004071:Digitalis Glycosides; D004073:Digitoxigenin; C012114:ASI-222; D004077:Digoxin