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.
- 4-aminopyridine,
- action
- animals;
- biosynthesis/drug
- blockers,
- cardiac,
- cell
- channel
- channels,
- death,
- dogs;
- down-regulation,
- drug
- effects;
- electrocardiography;
- electrophysiology;
- female;
- infarction,
- male;
- myocardial
- myocytes,
- pathology/physiology;
- pathology;
- pharmacology;
- physiology;
- physiopathology
- physiopathology;
- potassium
- potentials,
- separation;
- sudden,
- tachycardia,
- ventricular,
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