ST segment elevation by current-to-load mismatch: An experimental and computational study

Mark G. Hoogendijk, Mark Potse, Alain Vinet, Jacques M.T. De Bakker, Ruben Coronel

Research output: Contribution to journalArticleAcademicpeer-review

69 Citations (Scopus)

Abstract

Background Recently, we demonstrated that ajmaline caused ST segment elevation in the heart of an SCN5A mutation carrier by excitation failure in structurally discontinuous myocardium. In patients with Brugada syndrome, ST segment elevation is modulated by cardiac sodium (INa), transient outward (Ito), and L-type calcium currents (ICaL). Objective To establish experimentally whether excitation failure by current-to-load mismatch causes ST segment elevation and is modulated by I to and ICaL. Methods In porcine epicardial shavings, isthmuses of 0.9, 1.1, or 1.3 mm in width were created parallel to the fiber orientation. Local activation was recorded electrically or optically (di-4-ANEPPS) simultaneously with a pseudo-electrocardiogram (ECG) before and after ajmaline application. Intra- and extracellular potentials and ECGs were simulated in a computer model of the heart and thorax before and after introduction of right ventricular structural discontinuities and during varying levels of INa, Ito, and ICaL. Results In epicardial shavings, conduction blocked after ajmaline in a frequency-dependent manner in all preparations with isthmuses ≤1.1 mm width. Total conduction block occurred in three of four preparations with isthmuses of 0.9 mm versus one of seven with isthmuses <1.1 mm (P<.05). Excitation failure resulted in ST segment elevation on the pseudo-ECG. In computer simulations, subepicardial structural discontinuities caused local activation delay and made the success of conduction sensitive to INa, Ito, and ICaL. Reduction of Ito and increase of ICaL resulted in a higher excitatory current, overcame subepicardial excitation failure, and reduced the ST segment elevation. Conclusions Excitation failure by current-to-load mismatch causes ST segment elevation and, like ST segment elevation in Brugada patients, is modulated by Ito and ICaL.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalHeart Rhythm
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Netherlands Heart Foundation ( 2008B062 to RC) and by the Interuniversity Cardiology Institute of the Netherlands. Computational resources were provided by the Réseau Québécois de Calcul de Haute Performance.

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