Hysteresis effect implicates calcium cycling as a mechanism of repolarization alternans

Circulation
Mariah L WalkerD S Rosenbaum

Abstract

T-wave alternans is due to alternation of membrane repolarization at the cellular level and is a risk factor for sudden cardiac death. Recently, a hysteresis effect has been reported in patients whereby T-wave alternans, once induced by rapid heart rate, persists even when heart rate is subsequently slowed. We hypothesized that alternans hysteresis is an intrinsic property of cardiac myocytes, directly related to an underlying mechanism for repolarization alternans that involves intracellular calcium cycling. Stepwise pacing was used to induce alternans in Langendorff-perfused guinea pig hearts from which optical action potentials were recorded simultaneously at 256 ventricular sites with voltage-sensitive dyes and in whole-cell patch-clamped cardiac myocytes treated with or without BAPTA-AM (1,2-bis[2-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid tetrakis [acetoxymethyl ester]). Alternans hysteresis was observed in every isolated heart: threshold heart rate for alternans was 280+/-12 bpm, but during subsequent deceleration of pacing, alternans persisted to significantly slower heart rates (238+/-5 bpm, P<0.05). Optical mapping showed that this effect also applied to the threshold for spatially discordant alternans (313+/-2.2 ...Continue Reading

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Related Concepts

1,2-bis(2-aminophenoxy)ethane N, N, N', N'-tetraacetic acid acetoxymethyl ester
Nerve Impulses
Calcium
Cardiac Pacing, Artificial
Cell Separation
Metal Antagonists
Dose-Response Relationship, Drug
Egtazic Acid Sodium Salt
Electrocardiographic Recorders
Cavia porcellus

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