Mechanism of origin of conduction disturbances in aging human atrial bundles: Experimental and model study

Madison S. Spach, J. Francis Heidlage, Paul C. Dolber, Roger C. Barr

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site before a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue is unknown. Objective: The objective of this study was to determine if the pattern of cellular connectivity in aging human atrial bundles produces a mechanism for variable early premature responses. Methods: Extracellular and intracellular potentials were recorded after control and premature stimuli at a single site in aging human atrial bundles. We also measured cellular geometry, the distribution of connexins, and the distribution of collagenous septa. A model of the atrial bundles was constructed based on the morphological results. Action potential propagation and the sodium current were analyzed after premature stimuli in the model. Results: Similar extracellular potential waveform responses occurred after early premature stimuli in the aging bundles and in the model. Variable premature conduction patterns were accounted for by the single model of aging atrial structure. A major feature of the model results was that the conduction events and the magnitude of the sodium current at multiple sites were very sensitive to small changes in the location and the timing of premature stimuli. Conclusion: In aging human atrial bundles stimulated from only a single site, premature stimuli induce variable arrhythmogenic conduction responses. The generation of these responses is greatly enhanced by remodeling of cellular connectivity during aging. The results provide insight into sodium current structural interactions as a general mechanism of arrhythmogenic atrial responses to premature stimuli.

Original languageEnglish (US)
Pages (from-to)175-185
Number of pages11
JournalHeart Rhythm
Volume4
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Fingerprint

Theoretical Models
Sodium
Connexins
Tachycardia
Atrial Fibrillation
Action Potentials
Cardiac Arrhythmias

Keywords

  • Aging atrium
  • Arrhythmias
  • Cellular connectivity
  • Decremental conduction
  • Microfibrosis
  • Premature excitation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mechanism of origin of conduction disturbances in aging human atrial bundles : Experimental and model study. / Spach, Madison S.; Heidlage, J. Francis; Dolber, Paul C.; Barr, Roger C.

In: Heart Rhythm, Vol. 4, No. 2, 02.2007, p. 175-185.

Research output: Contribution to journalArticle

Spach, Madison S. ; Heidlage, J. Francis ; Dolber, Paul C. ; Barr, Roger C. / Mechanism of origin of conduction disturbances in aging human atrial bundles : Experimental and model study. In: Heart Rhythm. 2007 ; Vol. 4, No. 2. pp. 175-185.
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