The factors responsible for the ST-T wave alternans (STTA) and associated arrhythmias during acute ischemia have not been clarified.In acutely ischemic porcine myocardium, we recorded transmural unipolar and bipolar electrocardiograms and mid-myocardial extracellular K(+) ([K(+)]e) from the center of the ischemic zone during 8-minute episodes of ischemia. Two different STTAs occurred. The initial STTA, which occurred at 4 minutes 15 seconds ± 12 seconds of ischemia during sinus rhythm, was most prominent in the subendocardium, independent of [K(+)]e and activation block, and heart rate dependent. It occurred in 13/19 (68%) occlusions at heart rates ≤ 100 bpm and in 22/23 (96%) at > 100 bpm. The second STTA was more obvious and greatest in the subepicardium. It began in the later phase of ischemia and was also heart rate dependent (5/19 [26%] occlusions at heart rates ≤ 100 bpm and 10/23 [44%] at > 100 bpm). This STTA was consistently associated with 2:1 change in the bipolar electrogram morphology, possibly due to 2:1 conduction block. Ventricular fibrillation (VF) occurred only at > 100 bpm.The initial STTA may be independent of conduction abnormalities and represent primary repolarization alternans. The second STTA may be secondary to and indicative of 2:1 activation block or marked alternans of the action potential amplitude/duration. The associated VF most likely reflects the underlying conduction abnormality.

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