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 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.