Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine/Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA.
Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H824-31. doi: 10.1152/ajpheart.00407.2010. Epub 2011 Jul 1.
Diastolic heart failure is a major cause of mortality in the elderly population. It is often preceded by diastolic dysfunction, which is characterized by impaired active relaxation and increased stiffness. We tested the hypothesis that senescence-prone (SAMP8) mice would develop diastolic dysfunction compared with senescence-resistant controls (SAMR1). Pulsed-wave Doppler imaging of the ratio of blood flow velocity through the mitral valve during early (E) vs. late (A) diastole was reduced from 1.3 ± 0.03 in SAMR1 mice to 1.2 ± 0.03 in SAMP8 mice (P < 0.05). Tissue Doppler imaging of the early (E') and late (A') diastolic mitral annulus velocities found E' reduced from 25.7 ± 0.9 mm/s in SAMR1 to 21.1 ± 0.8 mm/s in SAMP8 mice and E'/A' similarly reduced from 1.1 ± 0.02 to 0.8 ± 0.03 in SAMR1 vs. SAMP8 mice, respectively (P < 0.05). Invasive hemodynamics revealed an increased slope of the end-diastolic pressure-volume relationship (0.5 ± 0.05 vs. 0.8 ± 0.14; P < 0.05), indicating increased left ventricular chamber stiffness. There were no differences in systolic function or mean arterial pressure; however, diastolic dysfunction was accompanied by increased fibrosis in the hearts of SAMP8 mice. In SAMR1 vs. SAMP8 mice, interstitial collagen area increased from 0.3 ± 0.04 to 0.8 ± 0.09% and perivascular collagen area increased from 1.0 ± 0.11 to 1.6 ± 0.14%. Transforming growth factor-β and connective tissue growth factor gene expression were increased in the hearts of SAMP8 mice (P < 0.05 for all data). In summary, SAMP8 mice show increased fibrosis and diastolic dysfunction similar to those seen in humans with aging and may represent a suitable model for future mechanistic studies.
舒张性心力衰竭是老年人群死亡的主要原因。它通常先于舒张功能障碍，其特征为主动松弛受损和僵硬度增加。我们测试了这样一个假设，即易感衰老（SAMP8）小鼠与抗衰（SAMR1）对照组相比会发展为舒张功能障碍。通过二尖瓣血流速度在早期（E）与晚期（A）舒张期的脉冲波多普勒成像，SAMR1 小鼠的比值从 1.3±0.03 降低到 SAMP8 小鼠的 1.2±0.03（P<0.05）。组织多普勒成像发现，SAMR1 小鼠的早期（E'）和晚期（A'）二尖瓣环速度从 25.7±0.9mm/s 降低到 SAMP8 小鼠的 21.1±0.8mm/s，E'/A'也分别从 SAMR1 小鼠的 1.1±0.02 降低到 0.8±0.03（P<0.05）。有创血流动力学显示舒张末期压力-容积关系斜率增加（0.5±0.05 比 0.8±0.14；P<0.05），提示左心室腔僵硬度增加。收缩功能或平均动脉压无差异；然而，舒张功能障碍伴有 SAMP8 小鼠心脏纤维化增加。SAMR1 与 SAMP8 小鼠相比，间质胶原面积从 0.3±0.04 增加到 0.8±0.09%，血管周围胶原面积从 1.0±0.11 增加到 1.6±0.14%。SAMP8 小鼠心脏中的转化生长因子-β和结缔组织生长因子基因表达增加（所有数据 P<0.05）。总之，SAMP8 小鼠表现出与人类衰老相似的纤维化和舒张功能障碍增加，可能是未来机制研究的合适模型。
