Pathophysiology and clinical implications of cardiac memory

Darwin Jeyaraj; Mahi Ashwath; David S Rosenbaum

doi:10.1111/j.1540-8159.2009.02630.x

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Pathophysiology and clinical implications of cardiac memory

Journal article

Open access

Peer reviewed

Pathophysiology and clinical implications of cardiac memory

Darwin Jeyaraj, Mahi Ashwath and David S Rosenbaum

Pacing and clinical electrophysiology, Vol.33(3), pp.346-352

03/2010

DOI: 10.1111/j.1540-8159.2009.02630.x

PMCID: PMC2865579

PMID: 20025710

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https://www.ncbi.nlm.nih.gov/pmc/articles/2865579View

Open Access

Abstract

Altering the pattern of activation of the ventricle causes remodeling of the mechanical and electrical properties of the myocardium. The electrical remodeling is evident on the surface electrocardiogram as significant change in T-wave polarity following altered activation; this phenomenon is ascribed to as "T-wave memory" or "cardiac memory." The electrophysiological remodeling following altered activation is characterized by distinct changes in regions proximal (early-activated) versus distal (late-activated) to the site of altered activation. The early-activated region exhibits marked attenuation of epicardial phase 1 notch due to reduced expression of the transient outward potassium current (I(to)). This is attributed to electrotonic changes during altered activation, and angiotensin-mediated regulation of Kv4.3 (the pore-forming alpha subunit responsible for I(to)). The late-activated region exhibits the most significant action potential prolongation due to markedly increased mechanical strain through a mechano-electrical feedback mechanism. Consequently, regionally heterogeneous action potential remodeling occurs following altered activation. This enhances regional repolarization gradients that underlie the electrophysiological basis for T-wave memory. Further, recent clinical studies highlight detrimental consequences of altered activation including worsening mechanical function and increased susceptibility to arrhythmias. Future studies to identify molecular mechanisms that link electrotonic and mechanical strain-induced changes to cellular electrophysiology will provide important insights into the role of altered activation in regulating cardiac repolarization and arrhythmogenesis.

Action Potentials - physiology

Animals

Cardiac Pacing, Artificial

Connexins - physiology

Defibrillators, Implantable

Electrocardiography

Heart Conduction System - drug effects

Heart Conduction System - physiopathology

Humans

Potassium Channels - drug effects

Potassium Channels - physiology

Tachycardia, Ventricular - physiopathology

Tachycardia, Ventricular - therapy

Time Factors

Ventricular Remodeling - physiology

Details

Title: Subtitle: Pathophysiology and clinical implications of cardiac memory
Creators: Darwin Jeyaraj - Case Western Reserve University
Mahi Ashwath - Case Western Reserve University
David S Rosenbaum - Case Western Reserve University
Resource Type: Journal article
Publication Details: Pacing and clinical electrophysiology, Vol.33(3), pp.346-352
DOI: 10.1111/j.1540-8159.2009.02630.x
PMID: 20025710
PMCID: PMC2865579
NLM abbreviation: Pacing Clin Electrophysiol
ISSN: 0147-8389
eISSN: 1540-8159
Grant note: R01 HL054807 / NHLBI NIH HHS R01 HL054807-11 / NHLBI NIH HHS R01-HL54807 / NHLBI NIH HHS
Language: English
Date published: 03/2010
Academic Unit: Radiology; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359760502771

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