title: Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart.
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.
authors.affiliation: Department of Electrophysiology, Research Center of Montreal Heart Institute, Montreal, QC, Canada. mharada@riem.nagoya-u.ac.jp
authors.forename: Masahide
authors.initials: M
authors.lastname: Harada
authors.forename: Yukiomi
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Yuko S
authors.initials: YS
authors.lastname: Ishiguro
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takanari
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Yasuya
authors.initials: Y
authors.lastname: Inden
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Lee
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D055724:Electrophysiological Phenomena; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008839:Microelectrodes; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type