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Circulation

Cellular mechanisms of atrial contractile dysfunction caused by sustained atrial tachycardia.


PMID 9715865

Abstract

Transient atrial contractile dysfunction ("atrial stunning") follows conversion of atrial fibrillation (AF) to sinus rhythm and has significant clinical implications; however, the underlying mechanisms are poorly understood. We investigated the hypothesis that rapid atrial activation (as during AF) impairs cellular contractility and affects cellular Ca2+ handling. Edge detection and indo 1 fluorescence techniques were used to measure unloaded cell shortening and intracellular Ca2+ transients in atrial myocytes from control (Ctl) dogs and dogs subjected to atrial pacing at 400 bpm for 7 (P7) or 42 (P42) days. Atrial tachycardia reduced fractional cell shortening (0.1 Hz) from 7.3+/-0.4% (Ctl) to 4.3+/-0.3% and 2.0+/-0.3% in P7 and P42 dogs, respectively (P<0.01 for each). Resting [Ca2+]i was not altered in paced dogs, but the systolic Ca2+ transient was significantly reduced. Furthermore, cells from paced dogs showed slowed relaxation and use-dependent decreases of Ca2+ transients and cell shortening compared with cells from Ctl dogs. To determine whether changes in Ca2+ transients account fully for alterations in contractility, we varied [Ca2+]o to evaluate the relation between Ca2+ transients and cell shortening. Reductions in Ca2+ transients in Ctl cells reduced shortening to the level of paced cells; however, when Ca2+ transients in P42 cells were elevated to the range of Ctl cells, a significant reduction in cell shortening remained. Similar results were obtained in dogs that maintained 1:1 capture throughout the monitoring period and dogs that developed sustained AF over the course of the study. Sustained atrial tachycardia causes important reductions in cellular contractility, in part by impairing cellular Ca2+ handling and decreasing systolic Ca2+ transients. These results provide direct evidence for the concept that AF induces atrial contractile dysfunction by causing a tachycardia-induced atrial cardiomyopathy.

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