CELLULAR MECHANISMS OF ATRIAL CONTRACTILE DYSFUNCTION CAUSED BY SUSTAINED ATRIAL TACHYCARDIA

Background-Transient atrial contractile dysfunction (''atrial stunning '') follows conversion of atrial fibrillation (AF) to sinus rhythm and has significant clinical implications; however, the underlying mechan isms are poorly understood. We investigated the hypothesis that rapid atrial activation las during AF) impairs cellular contractility and af fects cellular Ca2+ handling. Methods and Results-Edge detection and i ndo 1 fluorescence techniques were used to measure unloaded cell short ening and intracellular Ca2+ transients in atrial myocytes from contro l (Ctl) dogs and dogs subjected to atrial pacing at 400 bpm for 7 (P7) or 42 (P42) days. Atrial tachycardia reduced fractional cell shorteni ng (0.1 Hz) from 7.3+/-0.4% (Ctl) to 4.3+/-0.3% and 2.0+/-0.3% in P7 a nd P42 dogs, respectively (P<0.01 for each). Resting [Ca2+](i) was not altered in paced dogs, but the systolic Ca2+ transient was significan tly reduced. Furthermore, cells from paced dogs showed slowed relaxati on 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 s hortening. Reductions in Ca2+ transients in Ctl cells reduced shorteni ng. 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 th at maintained 1:1 capture throughout the monitoring period and dogs th at developed sustained AF over the course of the study, Conclusions-Su stained atrial tachycardia causes important reductions in cellular con tractility, in part by impairing cellular Ca2+ handling and decreasing systolic Ca2+ transients. These results provide direct evidence for t he concept that AF induces atrial contractile dysfunction by causing a tachycardia-induced atrial cardiomyopathy.