Thorax Institute-Hospital Clínic, University of Barcelona (Cardiology Department) Institute of Biomedical Research August Pi iSunyer (IDIBAPS), Spain.
Cardiovasc Pathol. 2013 Mar-Apr;22(2):133-40. doi: 10.1016/j.carpath.2012.07.003. Epub 2012 Oct 1.
The mechanism of sudden cardiac death in patients with heart failure (HF) is uncertain. Both electrical instability and structural remodelling could be factors that lead to fatal arrhythmias. We sought to analyse the expression of the sodium (SCN5A) and potassium (KCND3) channels as well as the fibrosis content in the ventricles of human HF and of non-diseased hearts under different post-mortem intervals.
We analysed normal human hearts as controls [n=20 for the right ventricle (RV) and n=13 for the left ventricle (LV)] and human hearts from HF patients, which were obtained at the time of cardiac transplantation, as cases (n=48 for RV and n=34 for LV). Transcription of the SCN5A (probes SCN5A E4-5, E11-12, and E28) and KCND3 channels and of COLLAGEN I and III were assayed by real-time polymerase chain reaction. In addition, paraffin sections were used to analyse the percentage of collagen deposition in both cases and controls. KCND3 mRNA expression in the LV was lower in the cases than in controls (P<.001). Higher levels of SCN5A mRNA were found in the HF samples when analysed with probe SCN5A E4-5 (P<.05). SCN5A expression was lower in the controls with longer post-mortem interval (n=4) than in the controls with a shorter post- mortem interval (n=16, P<.01). KCND3 mRNA levels were also different between the two control groups (P<.05). Collagen deposition was higher in the LV tissues of the cases when compared to controls (P<.001), and it was higher in the LV from HF patients than in the RV (P<.05). Furthermore, collagen deposition was higher in the LV samples from patients with implanted cardiac defibrillator (ICD) therapy than in the LV of patients with no ICD therapy (P<.05).
These data indicate that ionic and structural remodelling could be pathophysiological mechanisms of cardiac arrhythmias in HF patients.
心力衰竭（HF）患者心源性猝死的机制尚不清楚。电不稳定性和结构重构都可能是导致致命性心律失常的因素。我们试图分析钠离子（SCN5A）和钾离子（KCND3）通道以及不同死后间隔时间人心力衰竭和非病变心脏心室中的纤维化含量的表达。
我们分析了正常人心作为对照[右心室（RV）n=20，左心室（LV）n=13]和HF 患者心脏作为病例（RV n=48，LV n=34），这些心脏是在心脏移植时获得的。通过实时聚合酶链反应检测 SCN5A（探针 SCN5A E4-5、E11-12 和 E28）和 KCND3 通道以及 COLLAGEN I 和 III 的转录。此外，使用石蜡切片分析病例和对照中胶原蛋白沉积的百分比。与对照组相比，LV 中的 KCND3 mRNA 表达在病例中较低（P<.001）。当用探针 SCN5A E4-5 分析时，HF 样本中的 SCN5A mRNA 水平较高（P<.05）。在具有较长死后间隔（n=4）的对照组中，SCN5A 表达低于具有较短死后间隔（n=16）的对照组（P<.01）。两个对照组之间 KCND3 mRNA 水平也存在差异（P<.05）。与对照组相比，病例的 LV 组织中胶原蛋白沉积较高（P<.001），HF 患者的 LV 中胶原蛋白沉积高于 RV（P<.05）。此外，植入式心脏除颤器（ICD）治疗的患者的 LV 样本中胶原蛋白沉积高于无 ICD 治疗的患者的 LV（P<.05）。
这些数据表明，离子和结构重构可能是 HF 患者心脏性心律失常的病理生理机制。
