Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

Masahide Harada, Yukiomi Tsuji, Yuko S. Ishiguro, Hiroki Takanari, Yusuke Okuno, Yasuya Inden, Haruo Honjo, Jong Kook Lee, Toyoaki Murohara, Ichiro Sakuma, Kaichiro Kamiya, Itsuo Kodama

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Abstract

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n = 18) and control (n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Original languageEnglish
Pages (from-to)H565-H573
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number2
DOIs
Publication statusPublished - 01-02-2011
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Harada, M., Tsuji, Y., Ishiguro, Y. S., Takanari, H., Okuno, Y., Inden, Y., Honjo, H., Lee, J. K., Murohara, T., Sakuma, I., Kamiya, K., & Kodama, I. (2011). Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart. American Journal of Physiology - Heart and Circulatory Physiology, 300(2), H565-H573. https://doi.org/10.1152/ajpheart.00209.2010