Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles.

Abstract

INTRODUCTION:

To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Ca(i) ) 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 (V(m) ) and Ca(i) transient on left ventricular endocardium. An I(KATP) 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 APD(90) prolongation and the corresponding Ca(i) overloading in the first postpacing beats. The duration of Ca(i) transient recovered to 50% (DCaT(50) ) and 90% (DCaT(90) ) in the first postpacing beats was significantly longer than baseline. Abnormal Ca(i) 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 Ca(i) amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Ca(i) transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF.

CONCLUSIONS:

I (KATP) channel activation along with Ca(i) 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.

• Authors: Liang Tang, Boyoung Joung, Masahiro Ogawa, Peng-Sheng Chen, Shien-Fong Lin
• Journal: Journal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 23 Issue 12 Pg. 1364-71 (Dec 2012) ISSN: 1540-8167 [Electronic] United States
• PMID: 22809087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Wiley Periodicals, Inc.

Chemical References

• Calcium

Topics

• Action Potentials
• Animals
• Calcium (metabolism)
• Calcium Signaling
• Female
• Heart Conduction System (physiopathology)
• Heart Rate
• Male
• Myocardial Ischemia (complications, physiopathology)
• Perfusion (methods)
• Rabbits
• Ventricular Fibrillation (complications, physiopathology)