Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, D-93055, Regensburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2012 May;385(5):473-80. doi: 10.1007/s00210-011-0723-x. Epub 2012 Feb 7.
Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1.5, and KvLQT1 were measured by real time PCR. Experimental heart failure was characterized by left ventricular dilatation (13 ± 1 mm vs. 9 ± 1, p < .001), depressed fractional shortening (25 ± 5% vs. 40 ± 4, p < .001), and left atrial remodeling with increased diameter (16 mm ± 2 vs. 12 ± 1, p = .002) and weight (1.3 g ± 0.2 vs. 0.5 ± 0.1, p = .01). A prolongation of P-wave (44 ± 5 ms vs. 40 ± 4, p = .001) and PQ-interval (73 ± 10 ms vs. 66 ± 9, p = .009) occurred. In heart failure, BNP mRNA levels showed a significant upregulation in the left ventricle and atrium (1.83 AU ±1.31 vs. 0.67 ± 0.65, p < .05 and 7.16 AU ±1.76 vs. 0.77 ± 0.48, p < .05). Left ventricular Kv1.5 mRNA was reduced by 50% (p < .001) and KvLQT1 was reduced by 70% (p < .001). rERG and Kv4.3 mRNA were unchanged (n = ns). In contrast, left atrial Kv4.3 and KvLQT1 were reduced by 70% (p < .001), whereas rERG and Kv1.5 were unchanged (p = ns). Significant correlations were present between BNP and K+-channel expressions. Heart failure is characterized by significant changes in the gene expression of repolarizing K+-currents with a differential atrial and ventricular pattern. These molecular changes occur together with changes in cardiac function, geometry, conduction, and BNP expression and provide a functional basis for electrical vulnerability in heart failure.
心力衰竭导致心脏发生电生理变化。复极化 K+电流的下调导致心脏动作电位延长。然而，对于心力衰竭心脏中心房和心室 K+通道的差异表达知之甚少。
十只兔子接受了 30 天的渐进性右心室快速起搏。获得数字化心电图和超声心动图。采集左心室和左心房组织，并通过实时 PCR 测量 BNP、Kv4.3、rERG、Kv1.5 和 KvLQT1 的 mRNA 水平。
实验性心力衰竭的特征是左心室扩张（13±1mm 与 9±1，p<0.001）、射血分数降低（25±5%与 40±4，p<0.001）和左心房重构，直径增大（16mm±2 与 12±1，p=0.002）和重量增加（1.3g±0.2 与 0.5g±0.1，p=0.01）。P 波（44±5ms 与 40±4，p=0.001）和 PQ 间期（73±10ms 与 66±9，p=0.009）延长。
心力衰竭时，左心室和左心房的 BNP mRNA 水平显著上调（1.83AU±1.31 与 0.67±0.65，p<0.05 和 7.16AU±1.76 与 0.77±0.48，p<0.05）。左心室 Kv1.5 mRNA 减少 50%（p<0.001），KvLQT1 减少 70%（p<0.001）。rERG 和 Kv4.3 mRNA 无变化（n=ns）。相反，左心房 Kv4.3 和 KvLQT1 减少 70%（p<0.001），而 rERG 和 Kv1.5 无变化（p=ns）。BNP 与 K+通道表达之间存在显著相关性。
心力衰竭的特征是复极化 K+电流的基因表达发生显著变化，具有不同的心房和心室模式。这些分子变化与心功能、几何形状、传导和 BNP 表达的变化同时发生，为心力衰竭中的电易损性提供了功能基础。
