Abstract
How early (EADs) and delayed after depolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1408-1415 |
| Number of pages | 8 |
| Journal | Biophysical Journal |
| Volume | 99 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 8 2010 |
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ASJC Scopus subject areas
- Biophysics
Cite this
So little source, so much sink : Requirements for afterdepolarizations to propagate in tissue. / Xie, Yuanfang; Sato, Daisuke; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.
In: Biophysical Journal, Vol. 99, No. 5, 08.09.2010, p. 1408-1415.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - So little source, so much sink
T2 - Requirements for afterdepolarizations to propagate in tissue
AU - Xie, Yuanfang
AU - Sato, Daisuke
AU - Garfinkel, Alan
AU - Qu, Zhilin
AU - Weiss, James N.
PY - 2010/9/8
Y1 - 2010/9/8
N2 - How early (EADs) and delayed after depolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.
AB - How early (EADs) and delayed after depolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.
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UR - http://www.scopus.com/inward/citedby.url?scp=77956585767&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2010.06.042
DO - 10.1016/j.bpj.2010.06.042
M3 - Article
C2 - 20816052
AN - SCOPUS:77956585767
VL - 99
SP - 1408
EP - 1415
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 5
ER -