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.
%0 Journal Article
%1 Srid_2008_1463
%A Sridhar, Arun
%A Nishijima, Yoshinori
%A Terentyev, Dmitry
%A Terentyeva, Radmila
%A Uelmen, Rebecca
%A Kukielka, Monica
%A Bonilla, Ingrid M
%A Robertson, Gail A
%A Gy�rke, Sandor
%A Billman, George E
%A Carnes, Cynthia A
%D 2008
%J Am J Physiol Regul Integr Comp Physiol
%K 4-Aminopyridine, Action Animals; Blockers, Cardiac, Cell Channel Channels, Death, Dogs; Down-Regulation, Electrocardiography; Electrophysiology; Female; Infarction, Male; Myocardial Myocytes, Potassium Potentials, Separation; Sudden, Tachycardia, Ventricular, biosynthesis/drug drug effects; pathology/physiology; pathology; pharmacology; physiology; physiopathology physiopathology;
%N 5
%P R1463--R1472
%R 10.1152/ajpregu.90583.2008
%T Repolarization abnormalities and afterdepolarizations in a canine
model of sudden cardiac death.
%U http://dx.doi.org/10.1152/ajpregu.90583.2008
%V 295
%X 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.
@article{Srid_2008_1463,
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.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Sridhar, Arun and Nishijima, Yoshinori and Terentyev, Dmitry and Terentyeva, Radmila and Uelmen, Rebecca and Kukielka, Monica and Bonilla, Ingrid M and Robertson, Gail A and Gy�rke, Sandor and Billman, George E and Carnes, Cynthia A},
biburl = {https://www.bibsonomy.org/bibtex/25838dde4f6428cd1487899ac0f2771fd/hake},
description = {The whole bibliography file I use.},
doi = {10.1152/ajpregu.90583.2008},
file = {Srid_2008_1463.pdf:Srid_2008_1463.pdf:PDF},
institution = {Davis Heart and Lung Research Institute, Ohio State University, Columbus,
Ohio 43210, USA.},
interhash = {09c22bde3eeba0916f2a32e3a34cd3d6},
intrahash = {5838dde4f6428cd1487899ac0f2771fd},
journal = {Am J Physiol Regul Integr Comp Physiol},
keywords = {4-Aminopyridine, Action Animals; Blockers, Cardiac, Cell Channel Channels, Death, Dogs; Down-Regulation, Electrocardiography; Electrophysiology; Female; Infarction, Male; Myocardial Myocytes, Potassium Potentials, Separation; Sudden, Tachycardia, Ventricular, biosynthesis/drug drug effects; pathology/physiology; pathology; pharmacology; physiology; physiopathology physiopathology;},
month = Nov,
number = 5,
pages = {R1463--R1472},
pdf = {Srid_2008_1463.pdf},
pii = {90583.2008},
pmid = {18768760},
timestamp = {2009-06-03T11:21:32.000+0200},
title = {Repolarization abnormalities and afterdepolarizations in a canine
model of sudden cardiac death.},
url = {http://dx.doi.org/10.1152/ajpregu.90583.2008},
volume = 295,
year = 2008
}