Apamin-sensitive potassium current modulates action potential duration restitution and arrhythmogenesis of failing rabbit ventricles

Yu Cheng Hsieh, Po Cheng Chang, Chia Hsiang Hsueh, Young Soo Lee, Changyu Shen, James N. Weiss, Zhenhui Chen, Tomohiko Ai, Shien-Fong Lin, Peng-Sheng Chen

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background-Apamin-sensitive K currents (IKAS) are upregulated in heart failure. We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and can reduce ventricular fibrillation duration in failing ventricles. Methods and Results-We simultaneously mapped membrane potential and intracellular Ca (Cai) in 7 rabbit hearts with pacing-induced heart failure and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nmol/L) infusion. Apamin did not change APD80 in normal ventricles, but prolonged APD80 in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length, but not at intermediate pacing cycle length. The maximal slope of APDR curve was 2.03 (95% confidence interval, 1.73-2.32) in failing ventricles and 1.26 (95% confidence interval, 1.13-1.40) in normal ventricles at baseline (P=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 (95% confidence interval, 1.01-1.84; P=0.018), whereas no significant changes were observed in normal ventricles. During ventricular fibrillation in failing ventricles, the number of phase singularities (baseline versus apamin, 4.0 versus 2.5), dominant frequency (13.0 versus 10.0 Hz), and ventricular fibrillation duration (160 versus 80 s) were all significantly (P<0.05) decreased by apamin. Conclusions-Apamin prolongs APD at long and short, but not at intermediate pacing cycle length in failing ventricles. IKAS upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve, which promotes the generation and maintenance of ventricular fibrillation.

Original languageEnglish
Pages (from-to)410-418
Number of pages9
JournalCirculation: Arrhythmia and Electrophysiology
Volume6
Issue number2
DOIs
StatePublished - Apr 2013

Fingerprint

Apamin
Action Potentials
Potassium
Rabbits
Ventricular Fibrillation
pamidronate
Confidence Intervals
Heart Failure
Membrane Potentials
Up-Regulation
Heart Rate
Maintenance

Keywords

  • Electrophysiology
  • Experimental models heart failure
  • Optical mapping
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Apamin-sensitive potassium current modulates action potential duration restitution and arrhythmogenesis of failing rabbit ventricles. / Hsieh, Yu Cheng; Chang, Po Cheng; Hsueh, Chia Hsiang; Lee, Young Soo; Shen, Changyu; Weiss, James N.; Chen, Zhenhui; Ai, Tomohiko; Lin, Shien-Fong; Chen, Peng-Sheng.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 6, No. 2, 04.2013, p. 410-418.

Research output: Contribution to journalArticle

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abstract = "Background-Apamin-sensitive K currents (IKAS) are upregulated in heart failure. We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and can reduce ventricular fibrillation duration in failing ventricles. Methods and Results-We simultaneously mapped membrane potential and intracellular Ca (Cai) in 7 rabbit hearts with pacing-induced heart failure and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nmol/L) infusion. Apamin did not change APD80 in normal ventricles, but prolonged APD80 in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length, but not at intermediate pacing cycle length. The maximal slope of APDR curve was 2.03 (95{\%} confidence interval, 1.73-2.32) in failing ventricles and 1.26 (95{\%} confidence interval, 1.13-1.40) in normal ventricles at baseline (P=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 (95{\%} confidence interval, 1.01-1.84; P=0.018), whereas no significant changes were observed in normal ventricles. During ventricular fibrillation in failing ventricles, the number of phase singularities (baseline versus apamin, 4.0 versus 2.5), dominant frequency (13.0 versus 10.0 Hz), and ventricular fibrillation duration (160 versus 80 s) were all significantly (P<0.05) decreased by apamin. Conclusions-Apamin prolongs APD at long and short, but not at intermediate pacing cycle length in failing ventricles. IKAS upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve, which promotes the generation and maintenance of ventricular fibrillation.",
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AU - Chang, Po Cheng

AU - Hsueh, Chia Hsiang

AU - Lee, Young Soo

AU - Shen, Changyu

AU - Weiss, James N.

AU - Chen, Zhenhui

AU - Ai, Tomohiko

AU - Lin, Shien-Fong

AU - Chen, Peng-Sheng

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AB - Background-Apamin-sensitive K currents (IKAS) are upregulated in heart failure. We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and can reduce ventricular fibrillation duration in failing ventricles. Methods and Results-We simultaneously mapped membrane potential and intracellular Ca (Cai) in 7 rabbit hearts with pacing-induced heart failure and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nmol/L) infusion. Apamin did not change APD80 in normal ventricles, but prolonged APD80 in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length, but not at intermediate pacing cycle length. The maximal slope of APDR curve was 2.03 (95% confidence interval, 1.73-2.32) in failing ventricles and 1.26 (95% confidence interval, 1.13-1.40) in normal ventricles at baseline (P=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 (95% confidence interval, 1.01-1.84; P=0.018), whereas no significant changes were observed in normal ventricles. During ventricular fibrillation in failing ventricles, the number of phase singularities (baseline versus apamin, 4.0 versus 2.5), dominant frequency (13.0 versus 10.0 Hz), and ventricular fibrillation duration (160 versus 80 s) were all significantly (P<0.05) decreased by apamin. Conclusions-Apamin prolongs APD at long and short, but not at intermediate pacing cycle length in failing ventricles. IKAS upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve, which promotes the generation and maintenance of ventricular fibrillation.

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KW - Experimental models heart failure

KW - Optical mapping

KW - Ventricular fibrillation

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