Effects of Cytochalasin D on Electrical Restitution and the Dynamics of Ventricular Fibrillation in Isolated Rabbit Heart

Hideki Hayashi, Yasushi Miyauchi, Chung Chuan Chou, Hrayr S. Karagueuzian, Peng-Sheng Chen, Shien-Fong Lin

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Introduction: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. Methods and Results: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 ± 26 msec, 171 ± 14 msec, and 177 ± 14 msec) and steepened maximum slope of the APDR curve (1.1 ± 0.2, 1.3 ± 0.2, and 1.6 ± 0.4 for control, 5 μM, and 10 μM, respectively; P <0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 ± 0.6 Hz, 11.1 ± 2.4 Hz, and 9.8 ± 3.2 Hz for control, 5 μM, and 10 μM, respectively; P <0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 μM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 μM prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.

Original languageEnglish (US)
Pages (from-to)1077-1084
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume14
Issue number10
DOIs
StatePublished - Oct 2003
Externally publishedYes

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Cytochalasin D
Ventricular Fibrillation
Action Potentials
Rabbits
pamidronate
Microelectrodes
Membrane Potentials
Glass
Perfusion

Keywords

  • Action potentials
  • Electrophysiology
  • Fibrillation
  • Ventricle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

Effects of Cytochalasin D on Electrical Restitution and the Dynamics of Ventricular Fibrillation in Isolated Rabbit Heart. / Hayashi, Hideki; Miyauchi, Yasushi; Chou, Chung Chuan; Karagueuzian, Hrayr S.; Chen, Peng-Sheng; Lin, Shien-Fong.

In: Journal of Cardiovascular Electrophysiology, Vol. 14, No. 10, 10.2003, p. 1077-1084.

Research output: Contribution to journalArticle

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abstract = "Introduction: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. Methods and Results: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90{\%} repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 ± 26 msec, 171 ± 14 msec, and 177 ± 14 msec) and steepened maximum slope of the APDR curve (1.1 ± 0.2, 1.3 ± 0.2, and 1.6 ± 0.4 for control, 5 μM, and 10 μM, respectively; P <0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 ± 0.6 Hz, 11.1 ± 2.4 Hz, and 9.8 ± 3.2 Hz for control, 5 μM, and 10 μM, respectively; P <0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 μM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 μM prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.",
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AU - Hayashi, Hideki

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AU - Karagueuzian, Hrayr S.

AU - Chen, Peng-Sheng

AU - Lin, Shien-Fong

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N2 - Introduction: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. Methods and Results: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 ± 26 msec, 171 ± 14 msec, and 177 ± 14 msec) and steepened maximum slope of the APDR curve (1.1 ± 0.2, 1.3 ± 0.2, and 1.6 ± 0.4 for control, 5 μM, and 10 μM, respectively; P <0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 ± 0.6 Hz, 11.1 ± 2.4 Hz, and 9.8 ± 3.2 Hz for control, 5 μM, and 10 μM, respectively; P <0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 μM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 μM prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.

AB - Introduction: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. Methods and Results: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 ± 26 msec, 171 ± 14 msec, and 177 ± 14 msec) and steepened maximum slope of the APDR curve (1.1 ± 0.2, 1.3 ± 0.2, and 1.6 ± 0.4 for control, 5 μM, and 10 μM, respectively; P <0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 ± 0.6 Hz, 11.1 ± 2.4 Hz, and 9.8 ± 3.2 Hz for control, 5 μM, and 10 μM, respectively; P <0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 μM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 μM prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.

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