Sun H, Gaspo R, Leblanc N, Nattel S
Department of Medicine, Montreal Heart Institute and University of Montreal, Quebec, Canada.
Circulation. 1998 Aug 18;98(7):719-27. doi: 10.1161/01.cir.98.7.719.
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.
短暂性心房收缩功能障碍（“心房顿抑”）发生于心房颤动（AF）转复为窦性心律之后，具有重要的临床意义；然而，其潜在机制尚不清楚。我们研究了快速心房激动（如在AF期间）损害细胞收缩力并影响细胞钙（Ca2+）处理的假说。
采用边缘检测和indo 1荧光技术，测量对照（Ctl）犬以及以400次/分钟的频率进行心房起搏7天（P7）或42天（P42）的犬心房肌细胞的无负荷细胞缩短和细胞内Ca2+瞬变。心房心动过速使P7和P42犬的细胞缩短分数（0.1 Hz）分别从7.3±0.4%（Ctl）降至4.3±0.3%和2.0±0.3%（每组P<0.01）。起搏犬的静息细胞内钙浓度（[Ca2+]i）未改变，但收缩期Ca2+瞬变显著降低。此外，与Ctl犬的细胞相比，起搏犬的细胞舒张减慢，Ca2+瞬变和细胞缩短呈使用依赖性降低。为了确定Ca2+瞬变的变化是否完全解释了收缩力的改变，我们改变细胞外钙浓度（[Ca2+]o）来评估Ca2+瞬变与细胞缩短之间的关系。Ctl细胞中Ca2+瞬变的降低使缩短程度降至起搏细胞的水平；然而，当P42细胞中的Ca2+瞬变升高到Ctl细胞的范围时，细胞缩短仍显著降低。在整个监测期维持1:1夺获的犬以及在研究过程中发生持续性AF的犬中也获得了类似结果。
持续性心房心动过速导致细胞收缩力显著降低，部分原因是损害细胞Ca2+处理并降低收缩期Ca2+瞬变。这些结果为AF通过引起心动过速性心房心肌病导致心房收缩功能障碍这一概念提供了直接证据。
