title: Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death.
abstract: 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.
authors.affiliation: Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Sridhar
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishijima
authors.forename: Dmitry
authors.initials: D
authors.lastname: Terentyev
authors.forename: Radmila
authors.initials: R
authors.lastname: Terentyeva
authors.forename: Rebecca
authors.initials: R
authors.lastname: Uelmen
authors.forename: Monica
authors.initials: M
authors.lastname: Kukielka
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bonilla
authors.forename: Gail A
authors.initials: GA
authors.lastname: Robertson
authors.forename: Sandor
authors.initials: S
authors.lastname: Györke
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes