Journal
BIOPHYSICAL JOURNAL
Volume 92, Issue 2, Pages 448-460Publisher
BIOPHYSICAL SOCIETY
DOI: 10.1529/biophysj.106.091009
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL052319, R01HL066389, P01HL078931, R01HL071140, R01HL058533] Funding Source: NIH RePORTER
- NHLBI NIH HHS [P50 HL52319, P01 HL078931, P50 HL052319, R01 HL66389, R01 HL058533, R01 HL066389, R01 HL58533, R01 HL071140, R01 HL71140] Funding Source: Medline
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Alternans, a condition in which there is a beat-to-beat alternation in the electromechanical response of a periodically stimulated cardiac cell, has been linked to the genesis of life-threatening ventricular arrhythmias. Optical mapping of membrane voltage (V-m) and intracellular calcium (Ca-i) on the surface of animal hearts reveals complex spatial patterns of alternans. In particular, spatially discordant alternans has been observed in which regions with a large-small-large action potential duration (APD) alternate out-of-phase adjacent to regions of small-large-small APD. However, the underlying mechanisms that lead to the initiation of discordant alternans and govern its spatiotemporal properties are not well understood. Using mathematical modeling, we show that dynamic changes in the spatial distribution of discordant alternans can be used to pinpoint the underlying mechanisms. Optical mapping of V-m and Ca-i in paced rabbit hearts revealed that spatially discordant alternans induced by rapid pacing exhibits properties consistent with a purely dynamical mechanism as shown in theoretical studies. Our results support the viewpoint that spatially discordant alternans in the heart can be formed via a dynamical pattern formation process which does not require tissue heterogeneity.
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