The effect of the cardiac membrane potential on the rapid availability of the sodium-carrying system. J Physiol (Lond) 127: 213-224, 1955 20 Alterations in Canine Myocardial Excitability during Ischemia VICTOR ELHARRAR, PETER R. FOSTER, THOMAS L. JIRAK, WINSTON E. GAUM, AND DOUGLAS P. ZIPES SUMMARY Changes in the ventricular diastolic excitability threshold following occlusion of the left anterior descending coronary artery (LAD)were studied in open-chest anesthetized dogs by using a new automatic threshold-following pacemaker (ATFP). The ATFP measures the diastolic excitability threshold by successively decreasing the duration of regularly occurring pacing stimuli until the ventricle fails to respond. Under control conditions, the threshold stimulus duration was 60 ± 4 (mean ± SEM) /Lisec. In the first 1-3 minutes following occlusion of the LAD, the diastolic excitability threshold in the ischemic zone (IZ) decreased to 51 ± 5 fisec and then rapidly increased to 600 pisec at 5 minutes. The initial decrease in excitability threshold at IZ could be abolished by elevating the serum K + concentration prior to the LAD occlusion. These changes in excitability threshold at IZ could be prevented by infusing nonoxygenated solutions into the LAD at a site distal to the occlusion. As the excitability threshold increased in IZ during ischemia, the earliest time at which IZ could be reactivated by a stimulus with a voltage equal to twice the preligation diastolic voltage threshold was increased. In nine of 16 dogs, after 5 minutes of LAD ligation, the IZ to normal zone (NZ) activation time (when stimulating at IZ) exceeded the NZ to IZ activation time (when stimulating at NZ) by an average of 9 msec. We also found that in four dogs the NZ to IZ activation time exceeded the IZ to NZ activation time by an average of 10 msec. We conclude from these findings that a gradient of increasing excitability threshold exists as one moves from normally perfused toward more ischemic tissue, passing through a heterogeneous border zone that manifests some areas which have a decreased excitability threshold and other areas which have an increased excitability threshold, and that these changes in excitability importantly influence the determination of refractory period durations and conduction times.SEVERAL investigators have examined changes in refractory period duration and conduction that accompany