Abstract 1700: Potassium Current Abnormalities in a Canine Model of Post-Infarction Ventricular Fibrillation
We investigated myocyte electrophysiology in a canine healed myocardial infarction (MI) model of ischemia-induced ventricular fibrillation (VF).
METHODS: Dogs were classified (4 weeks after anterior wall MI) as susceptible (VF+, n=7) or resistant (VF-, n=3) to VF induced by a standardized exercise with superimposed ischemic protocol. Left ventricular mid-myocardial myocytes were isolated (2– 6 cm from infarct center) and studied using perforated whole cell patch clamp techniques at 36°C.
RESULTS: Average action potential duration (APD) was significantly prolonged in the VF+ group compared to the VF- group and controls (Panel A, p<0.05); with reduced resting membrane potential in the VF+ group compared to VF- or controls (p<0.05). Analysis of the beat-to-beat variability (Standard Deviation (SD) of APD90) in the action potential was performed and this was significantly greater in the VF+ animals compared to the control and the VF- group (Panel B). Inward rectifier current (IK1) conductance was reduced in the VF+ group compared to the VF- or control animals (p<0.05). The transient outward K+ current (Ito) was reduced in both the VF+ and VF- groups compared to controls (p<0.05). VF+ myocytes lacked any measurable IKr (p<0.05) while VF- myocytes had normal IKr. The slow component of the delayed rectifier (IKs) was significantly increased in VF+ (p<0.05) with a negative shift in the activation voltage.
CONCLUSIONS: The post-MI reduction in Ito is not associated with increased susceptibility to VF. AP changes in the VF+ myocytes are associated with loss of IKr, reduced IK1, increased IKs and increased beat-to-beat variability in the APD predisposing to ischemia induced VF.