Boehm Mario, Lawrie Allan, Wilhelm Jochen, Ghofrani Hossein A, Grimminger Friedrich, Weissmann Norbert, Seeger Werner, Schermuly Ralph T, Kojonazarov Baktybek
Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Giessen, Germany.
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Exp Physiol. 2017 Feb 1;102(2):180-189. doi: 10.1113/EP085963.
What is the central question of this study? The aim was to investigate whether complementary assessment of non-invasive ultrasound imaging together with closed chest-derived intracardiac pressure-volume catheterization is applicable to mice for an in-depth characterization of right ventricular (RV) function even upon maintained pressure overload. What is the main finding and its importance? Characterization of RV function by the complementary use of echocardiographic imaging together with pressure-volume catheterization reveals ventricular-arterial decoupling upon maintained pressure overload, where RV systolic function correlates with ventricular-arterial coupling rather than contractility, whereas diastolic function correlates well with RV diastolic pressure. This combined approach allows us to phenotype RV function and dysfunction better in genetically modified and/or pharmacologically treated mice. Assessment of right ventricular (RV) function in rodents is a challenge because of the complex RV anatomy and structure. To date, the best characterization of RV function has been achieved by accurate cardiovascular phenotyping, involving a combination of non-invasive imaging and intracardiac pressure-volume measurements. We sought to investigate the feasibility of two complementary phenotyping techniques for the evaluation of RV function in an experimental mouse model of sustained RV pressure overload. Mice underwent either sham surgery (n = 5) or pulmonary artery banding (n = 8) to induce isolated RV pressure overload. After 3 weeks, indices of RV function were assessed by echocardiography (Vevo2100) and closed chest-derived invasive pressure-volume measurements (PVR-1030). Pulmonary artery banding resulted in RV hypertrophy and dilatation accompanied by systolic and diastolic dysfunction. Invasive RV haemodynamic measurements demonstrated an increased end-systolic elastance and arterial elastance after pulmonary artery banding compared with sham operation, resulting in ventricular-arterial decoupling. Regression analysis revealed that tricuspid annular plane systolic excursion is correlated with ventricular-arterial coupling (r² = 0.77, P = 0.002) rather than with RV contractility (r² = -0.61, P = 0.07). Furthermore, the isovolumic relaxation time to ECG-derived R-R interval and the ratio of the early diastolic peak velocity measured by pulsed wave Doppler to the early diastolic peak obtained during tissue Doppler imaging correlate well with RV end-diastolic pressure (r² = 0.87, P = 0.0001 and r² = 0.82, P = 0.0009, respectively). Commonly used indices of systolic RV function are associated with RV-arterial coupling rather than contractility, whereas diastolic indices well correlate with end-diastolic pressure when there is maintained pressure overload.
本研究的核心问题是什么？目的是研究非侵入性超声成像与经胸心内压力-容积导管测量相结合的补充评估方法是否适用于小鼠，以便在压力负荷持续存在的情况下深入表征右心室（RV）功能。主要发现及其重要性是什么？通过超声心动图成像与压力-容积导管测量相结合来表征RV功能，发现在压力负荷持续存在时心室-动脉解耦，其中RV收缩功能与心室-动脉耦合相关而非与收缩性相关，而舒张功能与RV舒张压密切相关。这种联合方法使我们能够在基因改造和/或药物治疗的小鼠中更好地表征RV功能和功能障碍。由于RV解剖结构复杂，评估啮齿动物的右心室（RV）功能具有挑战性。迄今为止，通过精确的心血管表型分析，包括非侵入性成像和心内压力-容积测量的组合，已实现对RV功能的最佳表征。我们试图研究两种补充表型分析技术在持续RV压力超负荷实验小鼠模型中评估RV功能的可行性。小鼠接受假手术（n = 5）或肺动脉环扎术（n = 8）以诱导孤立的RV压力超负荷。3周后，通过超声心动图（Vevo2100）和经胸侵入性压力-容积测量（PVR-1030）评估RV功能指标。肺动脉环扎导致RV肥厚和扩张，并伴有收缩和舒张功能障碍。侵入性RV血流动力学测量显示，与假手术相比，肺动脉环扎后收缩末期弹性和动脉弹性增加，导致心室-动脉解耦。回归分析显示，三尖瓣环平面收缩期位移与心室-动脉耦合相关（r² = 0.77，P = 0.002），而与RV收缩性无关（r² = -0.61，P = 0.07）。此外，等容舒张时间与心电图衍生的R-R间期的比值以及脉冲波多普勒测量的舒张早期峰值速度与组织多普勒成像获得的舒张早期峰值的比值与RV舒张末期压力密切相关（分别为r² = 0.87，P = 0.0001和r² = 0.82，P = 0.0009）。常用的RV收缩功能指标与RV-动脉耦合相关而非与收缩性相关，而在压力负荷持续存在时，舒张指标与舒张末期压力密切相关。
