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From the Department of Medicine and Research Center, Montreal Heart
Institute and University of Montreal (H.S., R.G., N.L., S.N.); the Department
of Physiology, University of Montreal (N.L.); and the Department of
Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec,
Canada.
Correspondence to Dr Stanley Nattel, Research Center, Montreal Heart Institute, 5000 Bélanger St E, Montreal, Quebec, Canada H1T 1C8. E-mail nattel{at}icm.umontreal.ca
Background—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.
Methods and Results—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.
Conclusions—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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Cellular Mechanisms of Atrial Contractile Dysfunction Caused by Sustained Atrial Tachycardia
Key Words: arrhythmia • calcium • sarcoplasmic reticulum • cardiomyopathy
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