CHRONIC INHIBITION OF FATTY-ACID OXIDATION - NEW MODEL OF DIASTOLIC DYSFUNCTION
CHRONIC INHIBITION OF FATTY-ACID OXIDATION - NEW MODEL OF DIASTOLIC DYSFUNCTION
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DOI：
10.1152/ajpheart.1990.258.1.h51
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发表时间：
1990-01-01
影响因子：
--
通讯作者：
BRESSLER, R
中科院分区：
文献类型：
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作者：
LITWIN, SE;RAYA, TE;BRESSLER, R
本研究旨在确定由2-十四烷基缩水甘油酸（TDGA）抑制长链脂肪酸氧化引起的心脏变化。雄性Sprague-Dawley大鼠（n = 64）用TDGA（20 mg·kg-1·day-1）或相当体积的赋形剂通过管饲喂养处理7或21天。在清醒的大鼠中，TDGA不改变心率、左心室收缩压或舒张末期压、左心室压力发展（dP/dt）或左心室舒张时间常数。左心室发展压在21天时没有变化。TDGA增加左心室重量、左心室重量/体重比和总心脏重量/体重比。左心室内膜和心外膜肌细胞体积分别增加53%和65%。心肌甘油三酯含量增加三倍。舒张末期压0和30 mmHg之间的左心室腔室刚度常数增加，在7天和21天时，工作舒张末期压下的左心室舒张末期容积降低。心肌硬度常数在第7天和第21天也增加。因此，用TDGA抑制长链脂肪酸氧化增加了左心室质量，改变了左心室腔和肌肉僵硬度，而不改变左心室舒张或收缩功能。我们的结论是，长链脂肪酸氧化的抑制产生了一个不寻常的左心室肥大和舒张功能障碍的模型，其特征是被动弹性的性质异常，但保留放松。
This study was designed to determine the change 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.cntdot.kg-1.cntdot.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 ratioand 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.