EFFECTS OF CAFFEINE AND RYANODINE ON DELAYED AFTERDEPOLARIZATIONS AND SUSTAINED RHYTHMIC ACTIVITY IN 1-DAY-OLD MYOCARDIAL-INFARCTION IN THE DOG

Caffeine and ryanodine are known to modulate oscillatory release of Ca2+ from the sarcoplasmic reticulum. The effects of caffeine and ryanodine on delayed afterdepolarizations (DADs) and sustained rhythmic activity in subendocardial Purkinje fibers surviving 1-day-old myocardial infarction in the dog were studied with standard microelectrode techniques. In prepartions that showed sustained rhythmic activity, a high concentration of caffeine (10 mM) and ryanodine (10-7 and 10-6 M) slowed and terminated the sustained rhythmic activity and markedly suppressed DADs. An increase in the temperature of the tissue bath from 37° to 39°C did not change these results. In quiescent normal and infarcted preparations, a low concentration of caffeine (0.5 mM) differentially induced DADs in ischemic but not in normal Purkinje fibers, increased the amplitude of existing DADs, and brought subthreshold DADs to threshold potential that caused triggered activity. Our results are consistent with the hypothesis that triggered activity arising from DADs characterizes the sustained rhythmic activity in endocardial preparations 1 day after infarction and indicate an important role for the sarcoplasmic reticulum in the genesis of DADs and triggered activity in this model.