Persistent T-wave changes after alteration of the ventricular activation sequence. New insights into cellular mechanisms of 'cardiac memory'.

BACKGROUND "Cardiac memory" refers to persistent T-wave changes on ECG that follow resumption of sinus rhythm after a period of altered activation sequence. Previous studies demonstrated that cardiac memory in intact dogs was abolished by 4-aminopyridine (4-AP), which blocks both the transient outward potassium current, Ito, and IK. METHODS AND RESULTS We used standard microelectrode techniques to study the mechanism for cardiac memory in canine ventricular subepicardial and subendocardial slabs measuring 15 x 30 x 1 to 2 mm. Bipolar electrodes were used to stimulate slabs parallel to fiber axis, simulating normal activation, and perpendicular to fiber axis, simulating ventricular pacing. Four 30-minute periods of normal activation at a basic cycle length of 650 milliseconds were interrupted by three 20-minute periods of ventricular pacing at a basic cycle length of 450 milliseconds. We first recorded action potentials differentially from epicardial and endocardial slabs. The stimulation protocol induced changes in the "T" wave of the difference signals that mimicked cardiac memory and that could be explained on the basis of the transmural gradient in repolarization between epicardium and endocardium. This result was not obtainable with slow and rapid pacing from one site only. In subsequent experiments, action potential characteristics of epicardial and endocardial slabs were studied by the same pacing protocol with alternation between simulated normal activation and ventricular pacing. During ventricular pacing, the epicardial phase 1 notch and plateau amplitude decreased compared with normal activation. 4-AP (3 mmol/L) decreased notch size and plateau amplitude during normal activation in epicardium but not endocardium. In contrast, the local anesthetic lidocaine did not change notch size or plateau amplitude in epicardium or endocardium. CONCLUSIONS These results suggest that the contribution to repolarization of specific potassium channels influences the memory phenomenon and that by blocking Ito and reducing the transmural voltage gradient for repolarization, 4-AP abolishes cardiac memory.