Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA.
Cardiovasc Pathol. 2011 Nov-Dec;20(6):343-51. doi: 10.1016/j.carpath.2010.12.003. Epub 2011 Feb 4.
Glycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described.
The main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure-volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of (3)H-glucose to (3)H(2)O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs.
Results revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks.
The results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.
在左心室肥厚（LVH）和机械功能障碍进展过程中，鼠心中的糖酵解通量尚未被描述。
本研究的主要目的是描述胸主动脉结扎 3 周和 6 周对以下方面的影响：（1）通过压力-容积环分析量化的灌流工作心脏的左心室（LV）收缩和舒张功能；（2）作为（3）H-葡萄糖转化为（3）H2O 的速度表示的工作心脏中的糖酵解通量；（3）通过对光和电子显微镜照片的定量和定性分析评估 LV 活检的超微结构。
结果表明：（1）收缩功能指标，包括 LV 末期压力、心输出量、LV 压力发展和下降的速度，在 3 周和 6 周后结扎时被压抑到相似的程度；（2）舒张功能障碍，表现为 LV 末期压力和容积升高，在 6 周时比 3 周时更为严重，与衰竭的转变一致；（3）糖酵解通量逐渐下降，在 6 周后结扎时大致为对照率的一半；（4）结构紊乱，表现为间质胶原含量增加和肌节 Z 带破坏，在 3 周时比 6 周时更为明显。
这些结果与以下观点一致，即肌细胞损伤、纤维化和抑制糖酵解通量代表适应性结构和代谢重塑，导致在高压力负荷诱导的 LVH 中发生衰竭。
