Subepicardial transmembrane potentials were recorded from intact pig hearts to observe the changes induced by acute ischemia. Ischemia shortened action potential duration, and decreased its amplitude, upstroke velocity, and resting potential. The cells were unresponsive after 12 to 15 minutes of coronary artery occlusion, yet near normal action potentials could be restored by flushing the occluded artery with saline as late as 40 minutes after occlusion. The unipolar extracellular electrogram reflected unresponsiveness by a monophasic potential. Local refractory periods initially shortened by up to 100 msec. Later, postrepolarization refractoriness occurred and refractory periods lengthened often in excess of basic cycle length, thus resulting in 2:1 responses. The onset of early ventricular arrhythmias often coincided with a period of alternation and 2:1 responses, especially when these got out of phase in different regions. Reperfusion frequently led to ventricular fibrillation, and was associated with marked inhomogeneity in cellular responses. Re-entry within ischemic myocardium was the most likely mechanism for arrhythmias.

"Ischemic" blood was obtained in pigs from a local coronary vein on release of coronary artery occlusion. The effects of this blood on transmembrane potentials of muscle strips taken from the same heart were compared with control blood. Whereas action potentials remained stable in control blood, ischemic blood collected after more than 15 minutes of coronary occlusion produced shortening of action potential duration, reduction of resting potential, upstroke velocity and amplitude, then postrepolarization refractoriness and finally unresponsiveness. Ischemic blood collected after shorter periods of coronary occlusion produced only mild effects (shortening of action potential and postrepolarization refractoriness). These effects of ischemic blood could not be attributed to increased potassium concentration even in combination with acidosis, hypoxia and hypoglycemia. It appears that during ischemia unidentified factors are released which have potent depressant effects on the excitability of even normal myocardium.

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We recorded 60 DC simultaneous electrograms from isolated porcine and canine hearts in the first minutes after coronary occlusion. Ventricular premature beats (VPB) originated from the normal side of the ischemic border, which was frequently separated from the central ischemic area showing delayed activity by a small zone of inexcitable tissue. We attempted in a computer model to generate VPB's at one side of an area showing conduction block. In computer simulations,,, the presence of elements capable of automatic activity greatly facilitated the induction of VPB's. By coupling automatic elements to nonautomatic elements, overt pacemaking activity could be suppressed. Subthreshold depolarizations transmitted through a zone of conduction block could, when properly timed, trigger the latent automatic elements into overt automatic activity, resulting in single or repetitive VPB's. The ventricular premature beats in the intact hearts with acute regional ischemia may be caused by "triggered automaticity" in which the trigger is provided by the "injury current" flowing from ischemic cells showing delayed repolarization via a segment of inexcitable ischemic cells in the border zone to normally perfused cells with suppressed automaticity.

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