Cha Tae-Joon, Ehrlich Joachim R, Zhang Liming, Shi Yan-Fen, Tardif Jean-Claude, Leung Tack Ki, Nattel Stanley
5000 Belanger St East, Montreal, Quebec, H1T 1C8, Canada.
Circulation. 2004 Jan 27;109(3):412-8. doi: 10.1161/01.CIR.0000109501.47603.0C. Epub 2004 Jan 12.
Congestive heart failure (CHF) downregulates atrial transient outward (I(to)), slow delayed rectifier (I(Ks)), and L-type Ca(2+) (I(Ca,L)) currents and upregulates Na(+)-Ca(2+) exchange current (I(NCX)) (ionic remodeling) and causes atrial fibrosis (structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial.
We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing-induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6+/-1.2% (control), 36.2+/-2.3% (CHF, P<0.01), and 57.9+/-1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2+/-0.3 (control), 13.1+/-1.5 (CHF), and 2.4+/-0.4 (REC) mm Hg. CHF reduced I(to) density by approximately 65% (P<0.01), decreased I(Ca,L) density by approximately 50% (P<0.01), and diminished I(Ks) density by approximately 40% (P<0.01) while increasing I(NCX) density by approximately 110% (P<0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132+/-207 versus 14.3+/-8.8 seconds, control) and remained increased with REC (1014+/-252 seconds). Atrial fibrous tissue content also increased in CHF (2.1+/-0.2% for control versus 10.2+/-0.7% for CHF, P<0.01), with no recovery observed in REC (9.4+/-0.8%, P<0.01 versus control, P=NS versus CHF).
With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.
充血性心力衰竭（CHF）会下调心房瞬时外向电流（I(to)）、缓慢延迟整流电流（I(Ks)）和L型钙电流（I(Ca,L)），并上调钠钙交换电流（I(NCX)）（离子重塑），还会导致心房纤维化（结构重塑）。在CHF相关的心房颤动（AF）中，离子重塑与结构重塑的相对重要性存在争议。
我们测量了通过2周心室快速起搏（240次/分钟）诱导CHF的犬、起搏4周后恢复的CHF犬（REC）以及未起搏的对照犬的血流动力学和超声心动图参数、猝发起搏诱发AF的平均持续时间（DAF）以及心房肌细胞离子电流。左心室射血分数平均为58.6±1.2%（对照）、36.2±2.3%（CHF，P<0.01）和57.9±1.6%（REC），表明血流动力学完全恢复。同样，左心房压力分别为2.2±0.3（对照）、13.1±1.5（CHF）和2.4±0.4（REC）mmHg。CHF使I(to)密度降低约65%（P<0.01），I(Ca,L)密度降低约50%（P<0.01），I(Ks)密度降低约40%（P<0.01），同时I(NCX)密度增加约110%（P<0.05）。在REC中，所有离子电流密度均恢复至对照值。CHF时DAF增加（对照为14.3±8.8秒，CHF为1132±207秒），REC时仍保持增加（1014±252秒）。CHF时心房纤维组织含量也增加（对照为2.1±0.2%，CHF为10.2±0.7%，P<0.01），REC中未观察到恢复（9.4±0.8%，与对照相比P<0.01，与CHF相比P=NS）。
随着CHF的逆转，离子重塑完全恢复，但AF持续时间延长的底物和结构重塑仍然存在。这表明在实验性CHF中，结构重塑而非离子重塑是AF维持的主要因素。
