Department of Surgery and Physiology, University of Porto, Porto, Portugal.
Department of Systems Physiology, Ruhr University, Bochum, Germany.
Sci Rep. 2019 Feb 27;9(1):2956. doi: 10.1038/s41598-019-39581-9.
Aortic Stenosis (AS) is the most frequent valvulopathy in the western world. Traditionally aortic valve replacement (AVR) has been recommended immediately after the onset of heart failure (HF) symptoms. However, recent evidence suggests that AVR outcome can be improved if performed earlier. After AVR, the process of left ventricle (LV) reverse remodelling (RR) is variable and frequently incomplete. In this study, we aimed at detecting mechanism underlying the process of LV RR regarding myocardial structural, functional and molecular changes before the onset of HF symptoms. Wistar-Han rats were subjected to 7-weeks of ascending aortic-banding followed by a 2-week period of debanding to resemble AS-induced LV remodelling and the early events of AVR-induced RR, respectively. This resulted in 3 groups: Sham (n = 10), Banding (Ba, n = 15) and Debanding (Deb, n = 10). Concentric hypertrophy and diastolic dysfunction (DD) were patent in the Ba group. Aortic-debanding induced RR, which promoted LV functional recovery, while cardiac structure did not normalise. Cardiac parameters of RV dysfunction, assessed by echocardiography and at the cardiomyocyte level prevailed altered after debanding. After debanding, these alterations were accompanied by persistent changes in pathways associated to myocardial hypertrophy, fibrosis and LV inflammation. Aortic banding induced pulmonary arterial wall thickness to increase and correlates negatively with effort intolerance and positively with E/e' and left atrial area. We described dysregulated pathways in LV and RV remodelling and RR after AVR. Importantly we showed important RV-side effects of aortic constriction, highlighting the impact that LV-reverse remodelling has on both ventricles.
主动脉瓣狭窄（AS）是西方世界最常见的瓣膜病。传统上，建议在出现心力衰竭（HF）症状后立即进行主动脉瓣置换（AVR）。然而，最近的证据表明，如果更早进行 AVR，可以改善 AVR 结果。AVR 后，左心室（LV）逆向重构（RR）的过程是可变的，并且经常不完整。在这项研究中，我们旨在检测 LV RR 过程的机制，涉及 HF 症状发作前心肌结构、功能和分子变化。Wistar-Han 大鼠接受了 7 周的升主动脉带缩窄，随后进行了 2 周的去带缩窄，分别模拟 AS 诱导的 LV 重塑和 AVR 诱导的 RR 的早期事件。这导致了 3 组：假手术（Sham，n=10）、带缩窄（Ba，n=15）和去带缩窄（Deb，n=10）。Ba 组存在向心性肥大和舒张功能障碍（DD）。主动脉去带缩窄诱导 RR，促进 LV 功能恢复，而心脏结构未恢复正常。通过超声心动图和心肌细胞水平评估 RV 功能障碍的心脏参数在去带缩窄后仍然改变。去带缩窄后，这些改变伴随着与心肌肥厚、纤维化和 LV 炎症相关的途径的持续变化。主动脉带缩窄导致肺动脉壁厚度增加，并与努力不耐受呈负相关，与 E/e'和左心房面积呈正相关。我们描述了 AVR 后 LV 和 RV 重塑和 RR 的失调途径。重要的是，我们显示了主动脉缩窄对 RV 的重要副作用，突出了 LV 逆向重塑对两个心室的影响。
