Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death

Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD); a healed myocardial infarction increases the risk of SCD. We determined the contribution of specific repolarization abnormalities to ventricular tachyarrhythmias in a postinfarction model of SCD. For our methods, we used a postinfarction canine model of SCD, where an exercise and ischemia test was used to stratify animals as either susceptible (VF⁺) or resistant (VF^-) to sustained ventricular tachyarrhythmias. Our results show no changes in global left ventricular contractility or volumes occurred after infarction. At 8-10 wk postmyocardial infarction, myocytes were isolated from the left ventricular midmyocardial wall and studied. In the VF⁺ animals, myocyte action potential (AP) prolongation occurred at 50 and 90% repolarization (P < 0.05) and was associated with increased variability of AP duration and afterdepolarizations. Multiple repolarizing K⁺ currents (I_Kr, I_to) and inward I _K1 were also reduced (P < 0.05) in myocytes from VF⁺ animals compared with control, noninfarcted dogs. In contrast, only I _to was reduced in VF^- myocytes compared with controls (P < 0.05). While afterdepolarizations were not elicited at baseline in myocytes from VF^- animals, afterdepolarizations were consistently elicited after the addition of an I_Kr blocker. In conclusion, the loss of repolarization reserve via reductions in multiple repolarizing currents in the VF⁺ myocytes leads to AP prolongation, repolarization instability, and afterdepolarizations in myocytes from animals susceptible to SCD. These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias.