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Title: Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via β1-adrenoceptor activation in the crystalloid perfused normal rabbit heart
Authors: Winter, James
Brack, Kieran E.
Coote, J. H.
Ng, G. André
First Published: 8-Jan-2014
Publisher: Elsevier, International Society for Adult Congenital Heart Disease
Citation: International Journal of Cardiology, 2014, 172 (1), pp. 144-154
Abstract: BACKGROUND/OBJECTIVES: Cardiac contractility modulation (CCM) is a new treatment being developed for heart failure (HF) involving application of electrical current during the absolute refractory period. We have previously shown that CCM increases ventricular force through β1-adrenoceptor activation in the whole heart, a potential pro-arrhythmic mechanism. This study aimed to investigate the effect of CCM on ventricular fibrillation susceptibility. METHODS: Experiments were conducted in isolated New Zealand white rabbit hearts (2.0-2.5 kg, n=25). The effects of CCM (± 20 mA, 10 ms phase duration) on the left ventricular basal and apical monophasic action potential duration (MAPD) were assessed during constant pacing (200 bpm). Ventricular fibrillation threshold (VFT) was defined as the minimum current required to induce sustained VF with rapid pacing (30 × 30 ms). Protocols were repeated during perfusion of the β1-adrenoceptor antagonist metoprolol (1.8 μM). In separate hearts, the dynamic and spatial electrophysiological effects of CCM were assessed using optical mapping with di-4-ANEPPS. RESULTS: CCM significantly shortened MAPD close to the stimulation site (Basal: 102 ± 5 [CCM] vs. 131 ± 6 [Control] ms, P<0.001). VFT was reduced during CCM (2.6 ± 0.6 [CCM] vs. 6.1 ± 0.8 [Control] mA, P<0.01) and was correlated (r(2)=0.40, P<0.01) with increased MAPD dispersion (26 ± 4 [CCM] vs. 5 ± 1 [Control] ms, P<0.01) (n=8). Optical mapping revealed greater spread of CCM induced MAPD shortening during basal vs. apical stimulation. CCM effects were abolished by metoprolol and exogenous acetylcholine. No evidence for direct electrotonic modulation of APD was found, with APD adaptation occurring secondary to adrenergic stimulation. CONCLUSIONS: CCM decreases VFT in a manner associated with increased MAPD dispersion in the crystalloid perfused normal rabbit heart.
DOI Link: 10.1016/j.ijcard.2013.12.184
ISSN: 0167-5273
eISSN: 1874-1754
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd. Under a Creative Commons license ( )
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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