Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (O.R.C.-F., R.V., T.G.N., R.K.); Department of Internal Medicine, State University of Campinas (UNICAMP), São Paulo, Brazil (O.R.C.-F., H.M.); Departments of Pathology (R.M.) and Radiology (M.J.-H.), Brigham and Women's Hospital, Boston, MA; and Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (B.S., A.R., S.D.).
Circulation. 2013 Sep 10;128(11):1225-33. doi: 10.1161/CIRCULATIONAHA.112.000438. Epub 2013 Aug 2.
Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy.
Two murine models of hypertension (n=18, with n=15 controls) induced by l-N(G)-nitroarginine methyl ester (L-NAME) and pressure overload (n=11) from transaortic constriction (TAC) were imaged by cardiac magnetic resonance at baseline and 7 weeks after L-NAME treatment or up to 7 weeks after TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size-dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin-stained sections. The τic correlated strongly with histological cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75, P<0.001). Histological cardiomyocyte diameters and cell volumes were higher in mice treated with L-NAME compared with controls (P<0.001). In the TAC model, cardiac magnetic resonance and histology showed cell hypertrophy at 2 weeks after TAC without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic between 2 and 7 weeks after TAC.
The τic measured by contrast-enhanced cardiac magnetic resonance provides a noninvasive measure of cardiomyocyte hypertrophy. Extracellular volume fraction and τic can track myocardial tissue remodeling from pressure overload.
心肌细胞肥大是心力衰竭发展的关键前体。非侵入性表型细胞肥大的方法有限。本研究旨在验证一种基于心脏磁共振的方法，用于联合评估细胞外基质扩张和心肌细胞肥大。
通过心脏磁共振，在 l-N(G)-硝基精氨酸甲酯 (L-NAME) 诱导的高血压（n=18，n=15 个对照组）和主动脉缩窄（TAC）诱导的压力超负荷（n=11）两种小鼠模型中，分别在 L-NAME 治疗后 7 周和 TAC 后 7 周进行基线和随访成像。在钆对比前后测量 T1 弛豫时间。通过跨细胞膜水交换模型，测量水的细胞内寿命（τic）和细胞外体积分数（间质纤维化的标志物）。在 FITC-麦胚凝集素染色切片上测量心肌细胞直径和长度。τic 与组织学心肌细胞体积-表面积比（r=0.78，P<0.001）和细胞体积（r=0.75，P<0.001）高度相关。与对照组相比，L-NAME 处理的小鼠心肌细胞直径和细胞体积更大（P<0.001）。在 TAC 模型中，心脏磁共振和组织学在 TAC 后 2 周显示出细胞肥大，但在这个早期时间点没有明显的纤维化。在 TAC 后 2 至 7 周期间，暴露于 TAC 的小鼠表现出组织学细胞体积、体积-表面积比和 τic 的显著、纵向和平行增加。
通过对比增强心脏磁共振测量的 τic 提供了一种非侵入性的心肌细胞肥大测量方法。细胞外体积分数和 τic 可以跟踪心肌组织从压力超负荷引起的重塑。
