Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

Hideki Hayashi, Santosh Dora Kamanu, Norihiko Ono, Ayaka Kawase, Chung Chuan Chou, James N. Weiss, Hrayr S. Karagueuzian, Shien-Fong Lin, Peng-Sheng Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Single strong premature electrical stimulation (S2) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. Methods: We simultaneously mapped optical membrane potential (Vm) and intracellular Ca (Cai) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S1) and a cathodal S2 (40-80 mA) were given at different epicardial sites with a coupling interval of 135 ± 20 ms. Results: In all 6 hearts, S2 induced graded responses around the S2 site. These graded responses propagated locally toward the S1 site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S2. At the side of S2 opposite to the S1, the graded responses prolonged AP duration while the Cai continued to decline, resulting in a Cai sinkhole (an area of low Cai). The Cai in the sinkhole then spontaneously increased, followed by a slow Vm depolarization with a take-off potential of -40 ± 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. Conclusion: We conclude that a strong premature stimulus can induce a Cai sinkhole at the entrance of the CCP. Spontaneous Cai elevation in the Cai sinkhole precedes the Vm depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry.

Original languageEnglish
Pages (from-to)116-123
Number of pages8
JournalHeart Rhythm
Volume5
Issue number1
DOIs
StatePublished - Jan 2008

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Electric Stimulation
Action Potentials
Rabbits
Calcium
Microelectrodes
Membrane Potentials

Keywords

  • Action potentials
  • Electrical stimulation
  • Mapping
  • Reentry
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles. / Hayashi, Hideki; Kamanu, Santosh Dora; Ono, Norihiko; Kawase, Ayaka; Chou, Chung Chuan; Weiss, James N.; Karagueuzian, Hrayr S.; Lin, Shien-Fong; Chen, Peng-Sheng.

In: Heart Rhythm, Vol. 5, No. 1, 01.2008, p. 116-123.

Research output: Contribution to journalArticle

Hayashi, Hideki ; Kamanu, Santosh Dora ; Ono, Norihiko ; Kawase, Ayaka ; Chou, Chung Chuan ; Weiss, James N. ; Karagueuzian, Hrayr S. ; Lin, Shien-Fong ; Chen, Peng-Sheng. / Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles. In: Heart Rhythm. 2008 ; Vol. 5, No. 1. pp. 116-123.
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T1 - Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

AU - Hayashi, Hideki

AU - Kamanu, Santosh Dora

AU - Ono, Norihiko

AU - Kawase, Ayaka

AU - Chou, Chung Chuan

AU - Weiss, James N.

AU - Karagueuzian, Hrayr S.

AU - Lin, Shien-Fong

AU - Chen, Peng-Sheng

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AB - Background: Single strong premature electrical stimulation (S2) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. Methods: We simultaneously mapped optical membrane potential (Vm) and intracellular Ca (Cai) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S1) and a cathodal S2 (40-80 mA) were given at different epicardial sites with a coupling interval of 135 ± 20 ms. Results: In all 6 hearts, S2 induced graded responses around the S2 site. These graded responses propagated locally toward the S1 site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S2. At the side of S2 opposite to the S1, the graded responses prolonged AP duration while the Cai continued to decline, resulting in a Cai sinkhole (an area of low Cai). The Cai in the sinkhole then spontaneously increased, followed by a slow Vm depolarization with a take-off potential of -40 ± 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. Conclusion: We conclude that a strong premature stimulus can induce a Cai sinkhole at the entrance of the CCP. Spontaneous Cai elevation in the Cai sinkhole precedes the Vm depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry.

KW - Action potentials

KW - Electrical stimulation

KW - Mapping

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KW - Ventricular fibrillation

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