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

Abstract

BACKGROUND:

Apamin-sensitive K currents (I(KAS)) 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 (Ca(i)) 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 APD(80) in normal ventricles, but prolonged APD(80) 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. I(KAS) 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.

• Authors: 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
• Journal: Circulation. Arrhythmia and electrophysiology (Circ Arrhythm Electrophysiol) Vol. 6 Issue 2 Pg. 410-8 (Apr 2013) ISSN: 1941-3084 [Electronic] United States
• PMID: 23420832 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apamin
• Potassium

Topics

• Action Potentials (drug effects, physiology)
• Animals
• Apamin (pharmacology)
• Disease Models, Animal
• Female
• Heart Rate (drug effects, physiology)
• Heart Ventricles (drug effects, physiopathology)
• Myocardium (metabolism)
• Potassium (metabolism)
• Rabbits
• Ventricular Fibrillation (drug therapy, physiopathology)