title: Abolition of digitalis tachyarrhythmias by caffeine.
abstract: Digitalis-induced ventricular tachyarrhythmias (VTAs) are believed to be due to oscillatory afterpotentials (OAPs) generated by an oscillatory release of calcium from the sarcoplasmic reticulum (SR). Caffeine blocks the calcium uptake into the SR and then may influence VTAs by depleting the SR stores of calcium. We studied the action of digitalis and caffeine, singly and in combination, in the isolated guinea pig heart perfused by means of a modified Langendorff apparatus. Digitalis (beta-methyldigoxin 1.27 X 10(-6) M) caused VTAs and ventricular fibrillation (VF) in all the hearts. Caffeine alone decreased heart rate but never caused VTAs. With the administration of digitalis and caffeine (1 mM), VTAs rarely developed and VF never occurs. With digitalis and higher concentration of caffeine (10 mM), neither VTAs nor VF were observed. In hearts with complete atrioventricular block, digitalis increased the ventricular rate from 143 +/- 10 to 270 +/- 13 beats/min (n = 8) in 12 +/- 1.9 min and provoked the appearance of multiple ventricular pacemakers. The addition of 10 mM caffeine to the digitalis-containing solution reduced the ventricular rate to 171 +/- 12 beats/min (P less than 0.001 vs. digitalis alone, not significant vs. control, n = 8) and abolished the digitalis-induced multiple pacemakers. Ventricular asystole was occasionally observed during the perfusion with digitalis + 10 mM caffeine. Caffeine alone did not modify the diastolic pressure, whereas caffeine and digitalis rapidly increase it. These results represent indirect evidence to support that SR plays an important role in the origin of the digitalis-induced VTAs.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004077:Digoxin / Q000031:analogs & derivatives*; D004336:Drug Antagonism; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007700:Kinetics; D008520:Medigoxin / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D002110:Caffeine; D004077:Digoxin; D008520:Medigoxin; D002118:Calcium