Platt Mathew J, Huber Jason S, Romanova Nadya, Brunt Keith R, Simpson Jeremy A
Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
IMPART Team Canada Investigator Network, Saint John, NB, Canada.
Front Physiol. 2018 May 15;9:472. doi: 10.3389/fphys.2018.00472. eCollection 2018.
A growing proportion of heart failure (HF) patients present with impairments in both ventricles. Experimental pressure-overload (i.e., transverse aortic constriction, TAC) induces left ventricle (LV) hypertrophy and failure, as well as right ventricle (RV) dysfunction. However, little is known about the coordinated progression of biventricular dysfunction that occurs in TAC. Here we investigated the time course of systolic and diastolic function in both the LV and RV concurrently to improve our understanding of the chronology of events in TAC. Hemodynamic, histological, and morphometric assessments were obtained from the LV and RV at 2, 4, 9, and 18 weeks post-surgery. Systolic pressures peaked in both ventricles at 4 weeks, thereafter steadily declining in the LV, while remaining elevated in the RV. The LV and RV followed different structural and functional timelines, suggesting the patterns in one ventricle are independent from the opposing ventricle. RV hypertrophy/fibrosis and pulmonary arterial remodeling confirmed a progressive right-sided pathology. We further identified both compensation and decompensation in the LV with persistent concentric hypertrophy in both phases. Finally, diastolic impairments in both ventricles manifested as an intricate progression of multiple parameters that were not in agreement until overt systolic failure was evident. We establish pulmonary hypertension was secondary to LV dysfunction, confirming TAC is a model of type II pulmonary hypertension. This study also challenges some common assumptions in experimental HF (e.g., the relationship between fibrosis and filling pressure) while addressing a knowledge gap with respect to temporality of RV remodeling in pressure-overload.
越来越多的心力衰竭（HF）患者同时出现双心室功能受损。实验性压力超负荷（即横断主动脉缩窄，TAC）会导致左心室（LV）肥厚和衰竭，以及右心室（RV）功能障碍。然而，对于TAC中发生的双心室功能障碍的协同进展了解甚少。在此，我们同时研究了左心室和右心室收缩和舒张功能的时间进程，以增进我们对TAC中事件发生顺序的理解。在术后2周、4周、9周和18周从左心室和右心室获取血流动力学、组织学和形态学评估数据。两个心室的收缩压在4周时达到峰值，此后左心室收缩压稳步下降，而右心室收缩压仍保持升高。左心室和右心室遵循不同的结构和功能时间线，这表明一个心室的模式独立于对侧心室。右心室肥厚/纤维化和肺动脉重塑证实了右侧病变的进展。我们还进一步确定了左心室在两个阶段均持续存在向心性肥厚的代偿和失代偿情况。最后，两个心室的舒张功能障碍表现为多个参数的复杂进展，直到明显出现收缩功能衰竭时这些参数才趋于一致。我们证实肺动脉高压继发于左心室功能障碍，确认TAC是II型肺动脉高压的模型。本研究还挑战了实验性心力衰竭中的一些常见假设（例如纤维化与充盈压之间的关系），同时填补了压力超负荷时右心室重塑时间方面的知识空白。
