Electrophysiologic Effects of Cocaine on Subendocardial Purkinje Fibers Surviving 1 Day of Myocardial Infarction

INTRODUCTION: Cocaine has been shown to have broad cardiovascular effects that could be life threatening. Most of the reported electrophysiologic effects of cocaine have been studied in normal but not infarcted myocardium. METHODS AND RESULTS: Using microelectrode techniques, we investigated the electrophysiologic effects of cocaine on endocardial canine Purkinje fibers that survived 1 day of myocardial infarction. In quiescent infarcted preparations, stimulated trains were followed by subthreshold delayed afterdepolarizations (DADs), in the presence of propranolol (1 microM). Cocaine (10 microM) decreased the amplitude of DADs from 6.1 +/- 1.8 mV to 3.0 +/- 1.3 mV (P < 0.05, n = 6). When stimulated preparations (n = 23) showing no triggered activity during control (+propranolol) were superfused with a low concentration of caffeine (1 mM) or high extracellular Ca2+ (8.1 mM), triggered activity was induced. Subsequent cocaine (10 microM) superfusion prevented the induction of caffeine- and high Ca(2+)-induced triggered activity. Cocaine's effects were reversible upon washout. In preparations that showed triggered activity during control conditions (+propranolol), the mean cycle length of triggered activity was 755 +/- 45 msec. Cocaine (10 microM) superfusion lengthened the cycle length to 1030 +/- 141 msec and terminated triggered activity with a subthreshold DAD (n = 12). In addition, cocaine and ryanodine (10 microM) suppressed triggered activity in a similar manner when tested in the same preparations (n = 4). During control conditions, cocaine did not cause any significant change on the rate of rise of action potential upstroke (from 55.6 +/- 24.3 to 54.5 +/- 28.6 V/sec, n = 8) and maximum diastolic potential (from -58.4 +/- 4.3 to -56.6 +/- 6.5 mV, n = 8). In the absence of propranolol, 50 microM but not 10 microM cocaine induced early afterdepolarizations in 62% of the preparations exhibiting triggered activity during control conditions. CONCLUSION: The results suggest that cocaine modulates DADs and triggered activity in infarcted endocardial fibers via direct inhibition of cyclic release of Ca2+ from sarcoplasmic reticulum (SR) independently from a local anesthetic or sympathomimetic effect. This SR inhibition could account for the myocardial depressant effect of cocaine. However, while cocaine suppressed DADs, its induction of EADs can precipitate malignant ventricular arrhythmias in the setting of cocaine overdose and infarction.