Journal
CIRCULATION
Volume 132, Issue 15, Pages 1377-1386Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.114.015125
Keywords
arrhythmias, cardiac; death, sudden, cardiac; ion channels
Funding
- National Institutes of Health grants [P01 HL78931, R01 HL71140, R41HL124741]
- Indiana University Health-Indiana University School of Medicine Strategic Research Initiative
- Medtronic-Zipes Endowment of the Indiana University
Ask authors/readers for more resources
Background-Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (I-KAS) is activated during hypokalemia and that I-KAS blockade is proarrhythmic. Methods and Results-Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD(80)) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD(80) versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased I-KAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Conclusions-Hypokalemia activates I-KAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. I-KAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available