Hagdorn Quint A J, Kurakula Kondababu, Koop Anne-Marie C, Bossers Guido P L, Mavrogiannis Emmanouil, van Leusden Tom, van der Feen Diederik E, de Boer Rudolf A, Goumans Marie-José T H, Berger Rolf M F
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Front Physiol. 2021 Feb 26;12:557514. doi: 10.3389/fphys.2021.557514. eCollection 2021.
Right ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction.
Wistar rats were subjected to aorto-caval shunt (ACS, = 23) or sham (control, = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed.
At 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGFβ1 and pSMAD2/3), or fibrosis were present at any time point.
In the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model.
右心室（RV）功能及衰竭是多种心血管疾病发病率和死亡率的关键决定因素。心肌纤维化被视为心力衰竭的一个促成因素，但其在右心室衰竭中的重要性受到了挑战。本研究旨在评估心肌纤维化是否驱动了从代偿性到失代偿性容量负荷诱导的右心室功能障碍的转变。
将Wistar大鼠进行主动脉-腔静脉分流术（ACS，n = 23）或假手术（对照组，n = 15），并在1个月、3个月或6个月后处死。进行超声心动图、右心室压力-容积分析、基因表达评估及心脏组织学检查。
6个月时，6/8只ACS大鼠（75%）出现右心室衰竭的临床体征（胸腔积液、腹水和/或肝水肿），而在1个月和3个月时，尚未出现右心室衰竭的体征。心输出量增加了两到三倍，双心室扩张发生，而左心室射血分数逐渐降低。在1个月和3个月时，右心室收缩末期弹性（Ees）保持不变，但在6个月时，右心室Ees大幅下降。在右心室，在任何时间点均未出现氧化应激、炎症、促纤维化信号（TGFβ1和pSMAD2/3）或纤维化。
在ACS大鼠模型中，长期容量负荷在1个月和3个月时最初耐受性良好，但在6个月时诱发了终末期右心室衰竭的明显临床体征。然而，并未出现心肌纤维化或促纤维化信号增加。这些发现表明，在该模型中，心肌纤维化不参与从代偿性到失代偿性右心室功能障碍的转变。
