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SUMMARY We used standard microelectrode techniques to record delayed afterdepolarizations (DAD) induced by ouabain (2 x 1 0 7 M) in isolated canine Purkinje fibers (PF) and studied the response of DAD to the fast Na* channel blocker, tetrodotoxin (TTX, 1 mg/liter); the slow channel blocker, verapamil (verap, 1 mg/liter); the putative Ca 2+ blocker, AHR-2666 (AHR, 45 mg/liter); and lidocaine (lido, 4 mg/liter), which increases steady state outward current and decreases background inward current. PF were driven at cycle lengths of 1000-200 msec. Ouabain superfusion for 30 minutes induced DAD with amplitudes of 17.0 ± 1.5 (mean ± SE) mV at a cycle length of 200 msec. TTX, verap, AHR, and lido all depressed DAD amplitude (P < 0.05). To intercompare the effects of the drugs, graphs were constructed relating DAD amplitude to basic cycle length, and the relative magnitude of effects of the drugs on DAD amplitude at all cycle lengths was tested using a nested analysis of variance. The effects of verap and AHR were equivalent, and both decreased DAD amplitude more at short (to 37% of ouabain control) than at long (to 76%) cycle lengths (P< 0.05). Lido had a different effect and decreased DAD nearly equivalently at short (to 64%) and long (to 75%) cycle lengths. The actions of TTX were intermediate between-and significantly different from-those of the other drugs (P < 0.05). AHR and verap appear to act similarly, by modifying the current responsible for DAD, whereas lido appears to act by a different mechanism, perhaps by increasing steady state outward current. The actions of TTX may be a result of its effect on the transient inward current or on a background current carried by Na * .

We studied epinephrine-induced delayed afterdepolarizations and triggered activity in atrial fibers from the canine coronary sinus to determine whether their responses to cardiac pacing would aid in formulating a uniform set of guidelines for differentiating this triggered activity from other arrhythmogenic mechanisms. We used standard microelectrode techniques and compared the delayed afterdepolarizations and triggered activity with those occurring in ouabain-superfused Purkinje fibers. Like Purkinje fibers, the frequency of triggering in the coronary sinus and the coupling interval of the first triggered beat were related directly to the basic drive cycle length, and the delayed afterdepolarization amplitude and frequency of triggering were related to the coupling interval of premature stimuli (S2). However, unlike Purkinje fibers, the coupling interval of the delayed afterdepolarization and of the first triggered beat were independent of the S2. Once initiated, triggered activity in the coronary sinus followed one of four rhythm patterns: in all four, the minimum and equilibrium cycle lengths were independent of the initiating cycle length. Triggered activity was terminated by overdrive and S2 pacing, especially by long episodes of overdrive at short cycle length. The first escape beat after overdrive was linearly related to the overdrive cycle length, resulting in overdrive acceleration. The return cycle length after S2 was linearly related to the S2 coupling interval. Because delayed afterdepolarizations and triggered activity in the coronary sinus respond differently to pacing from those in ouabain-superfused Purkinje fibers, triggered activity in general may not be identified by a uniform set of guidelines.

SUMMARY We studied the electrophysiologic characteristics of ventricular muscle and Purkinje fibers from the hearts of five patients undergoing cardiac transplantation. All five patients had congestive failure and coronary artery disease before surgery and were receiving digitalis therapy. Ventricular DURING the last 2 years we have obtained ventricles from patients undergoing cardiac transplantation. These cardiac tissues were well preserved and not subjected to local trauma at cardiac surgery. In this paper, we report the cellular electrophysiologic properties of myocardial and Purkinje fibers from these hearts and the response of these fibers to certain cardioactive drugs. Methods Hearts were obtained from five patients at cardiac transplantation. Informed consent was obtained from each patient.Patient I was a 49-year-old female who had acute rheumatic fever at 19 years of age and an acute myocardial infarction at 45 years of age, followed by coronary artery bypass surgery. Congestive heart failure developed and was treated with digoxin, but her health continued to deteriorate; during the 6 months before From her cardiac transplantation she had two episodes of ventricular fibrillation. Before transplantation, severe biventricular failure with poor contractility of both ventricles was demonstrated. Her medications included digoxin, quinidine and, just before surgery, lidocaine. Patient 2 was a 15-year-old female in whom tetralogy of Fallot was diagnosed at 3 months of age. At 4 months of age she underwent a shunt procedure to increase pulmonary blood flow. Approximately 2 years before cardiac transplantation she began having episodes of hemoptysis. Cardiac catheterization revealed an occluded shunt and she underwent open heart repair of tetralogy of Fallot, during which she had a large anterolateral myocardial infarction. Subsequently, cardiac catheterization revealed severe right and left ventricular dysfunction and a large anteroapical aneurysm. Because of persistent severe congestive failure, cardiac transplantation was performed. Her medications before transplantation were digoxin and furosemide.Patient 3 was a 48-year-old male who had an acute myocardial infarction at 41 years of age. One year later, he had left ventricular failure that required digitalis and diuretics. Five months before transplantation, coronary angiography showed complete occlusion of the right coronary artery and a 60% proximal occlusion of the left anterior descending artery. Because of severe coronary artery disease deemed not remediable by bypass techniques, and severe cardiomyopathy, cardiac transplantation was performed.Patient 4 was a 48-year-old male who had his first myocardial infarction at the age of 43 years. This was

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