Litwin S E, Raya T E, Gay R G, Bedotto J B, Bahl J J, Anderson P G, Goldman S, Bressler R
Department of Internal Medicine, Veterans Administration Medical Center, Tucson 85723.
Am J Physiol. 1990 Jan;258(1 Pt 2):H51-6. doi: 10.1152/ajpheart.1990.258.1.H51.
This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mg.kg-1.day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increased, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.
本研究旨在确定用2-十四烷基缩水甘油酸（TDGA）抑制长链脂肪酸氧化后心脏的变化。雄性Sprague-Dawley大鼠（n = 64）通过灌胃给予TDGA（20 mg·kg⁻¹·d⁻¹）或等量的赋形剂，持续7天或21天。在清醒大鼠中，TDGA对心率、左心室收缩压或舒张压、左心室压力变化率（dP/dt）或左心室舒张时间常数均无影响。21天时左心室舒张末压未发生变化。TDGA增加了左心室重量、左心室重量与体重之比以及全心重量与体重之比。左心室内膜和心外膜心肌细胞体积分别增加了53%和65%。心肌甘油三酯含量增加了两倍。在舒张末压为0至30 mmHg之间，左心室腔硬度常数增加，在7天和21天时，工作舒张末压下的左心室舒张末容积均降低。在7天和21天时心肌硬度常数也增加。因此，用TDGA抑制长链脂肪酸氧化增加了左心室质量，并改变了左心室腔和心肌硬度，而不改变左心室舒张或收缩功能。我们得出结论，抑制长链脂肪酸氧化产生了一种不寻常的左心室肥厚和舒张功能障碍模型，其特征为被动弹性特性异常但舒张功能保留。
