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

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Hoogendijk MG, Potse M, Vinet A, de Bakker JM, Coronel R

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

Heart Rhythm. 2011 Jan;8(1):111-8. doi: 10.1016/j.hrthm.2010.09.066. Epub 2010 Oct 30.

PubMed ID

20870038 [ View in PubMed

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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 (I(Na)), transient outward (I(to)), and L-type calcium currents (I(CaL)). OBJECTIVE: To establish experimentally whether excitation failure by current-to-load mismatch causes ST segment elevation and is modulated by I(to) and I(CaL). 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 I(Na), I(to), and I(CaL). RESULTS: In epicardial shavings, conduction blocked after ajmaline in a frequency-dependent manner in all preparations 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 I(Na), I(to), and I(CaL). Reduction of I(to) and increase of I(CaL) 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 I(to) and I(CaL).

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ajmaline	Sodium channel protein type 5 subunit alpha	Protein	Humans	Yes	Inhibitor	Details