DIETARY FATTY ACID MODULATION OF MYOCARDIAL FUNCTION AND INFLUENCES ON AGING

心肌细胞收缩期，跨膜作用 老年大鼠心肌细胞膜电位和胞浆钙瞬变延长 与年轻人的细胞相比。肌浆细胞比率 内质网对Ca ~（++）的摄取和Ca ~（++）刺激ATP酶的水平 活动随着衰老而减少，心脏对β- 肾上腺素能刺激随着年龄的增长而减少。拟将 “正常”的年龄相关的心脏功能变化和心脏功能的增加 随着年龄的增长，病理学可能与膜的改变有关， 可以通过膳食脂质改变来干预的组合物， 心肌细胞和细胞内膜。 神经刺激随年龄增长而增加。短期喂养n-3 老年大鼠和猴富含多不饱和脂肪酸（n-3 PUFA）的饮食 显著降低室性心律失常的发生率， 富含饱和脂肪的饮食（SAT）会导致心律失常。SAT饮食诱导 心肌需氧量显著增加，与收缩无关 在控制条件下运行。相比之下，O2需求非常低 n-3 PUFA饮食。冠状动脉舒张功能储备更大 n-3 PUFA饮食比SAT饮食更有效。这些差异不是由于 基础代谢或血管功能的任何变化， 细胞内Ca++稳态。本研究（1月开始） 1993），研究了饮食脂质调节对隔离的 心肌细胞膜，以测试是否总细胞内 Ca++或Ca++在细胞质和细胞器之间的再分布是 改变了胞浆游离钙荧光（indo-1）和颤搐 电刺激离体心肌细胞的振幅是 目前正在从n-3 PUFA或饱和脂肪饮食治疗中测量 大鼠（6、12、24 mo）。对高低压力的反应性 BAYK 8644（L-型Ca++通道激动剂）， 异丙肾上腺素（β-肾上腺素能受体激动剂）和缺氧也 在这些群体中进行评估。细胞膜脂肪酸谱 目前正在进行分析，以确认变化的程度， 心肌膜脂质组成。

The period of cardiac myocyte contraction, the transmembrane action potential and cytosolic Ca++ transient are extended in old rat cardiac cells compared to those from young adults. The rate of sarcoplasmic reticulum uptake of Ca++ and the level of Ca++ stimulate ATPase activity decreases with senescence and the cardiac response to beta- adrenergic stimulation is reduced with aging. It is proposed that "normal" age-related changes in cardiac function and increased cardiac pathology with age may be associated with alterations to membrane composition which may be intervened by dietary lipid modification of myocardial cell and intracellular membranes.The vulnerability to arrhythmic stimuli increases with age. Short term feeding with n-3 polyunsaturated fatty acid (n-3 PUFA) rich diet in old rats and monkeys significantly reduces the incidence of ventricular arrhythmias whereas saturated fat rich diet (SAT) is pro-arrhythmogenic. SAT diet induces a marked increase in myocardial O2 demand independent of contractile function under control conditions. In contrast O2 demand was very low following n-3 PUFA diet. Coronary vasodilator reserve was greater following n-3 PUFA diet than SAT diet. These differences are not due to any change in basal metabolism or vascular function but rather to intracellular Ca++ homeostasis. The present study (commenced January 1993), investigates the effect of dietary lipid modulation in isolated cardiac myocyte membranes in order to test whether total intracellular Ca++ or Ca++ redistribution between the cytosol and organelles is altered. Cytosolic free calcium fluorescence (indo-1) and twitch amplitude of electrically stimulated isolated cardiac myocytes are currently being measured from n-3 PUFA or saturated fat dietary treated rats (6,12,24 mo). The responsiveness to the stresses of high and low stimulation rates (0.5,2Hz), BAYK8644 (L-type Ca++ channel agonist), isoproterenol (beta-adrenergic receptor agonist) and hypoxia is also to be assessed in these groups. Cell membrane fatty acid profile analysis is currently in progress to confirm the extent of change to cardiac membrane lipid composition.