Abstract
Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.
| Original language | English |
|---|---|
| Pages (from-to) | 1364-1371 |
| Number of pages | 8 |
| Journal | Journal of Cardiovascular Electrophysiology |
| Volume | 23 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2012 Dec 1 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
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Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles. / Tang, Liang; Joung, Boyoung; Ogawa, Masahiro; Chen, Peng Sheng; Lin, Shien Fong.
In: Journal of Cardiovascular Electrophysiology, Vol. 23, No. 12, 01.12.2012, p. 1364-1371.Research output: Contribution to journal › Article
TY - JOUR
T1 - Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles
AU - Tang, Liang
AU - Joung, Boyoung
AU - Ogawa, Masahiro
AU - Chen, Peng Sheng
AU - Lin, Shien Fong
PY - 2012/12/1
Y1 - 2012/12/1
N2 - Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.
AB - Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.
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UR - http://www.scopus.com/inward/citedby.url?scp=84871211062&partnerID=8YFLogxK
U2 - 10.1111/j.1540-8167.2012.02400.x
DO - 10.1111/j.1540-8167.2012.02400.x
M3 - Article
C2 - 22809087
AN - SCOPUS:84871211062
VL - 23
SP - 1364
EP - 1371
JO - Journal of Cardiovascular Electrophysiology
JF - Journal of Cardiovascular Electrophysiology
SN - 1045-3873
IS - 12
ER -