AJP - Heart and Circulatory Physiology, Vol 244, Issue 2 215-H221, Copyright © 1983 by American Physiological Society
Abolition of digitalis tachyarrhythmias by caffeine
M. Di Gennaro, R. Valle, M. Pahor and P. Carbonin
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.
