EFFECTS OF FREE FATTY-ACIDS AND DICHLOROACETATE ON ISOLATED WORKING DIABETIC RAT-HEART
EFFECTS OF FREE FATTY-ACIDS AND DICHLOROACETATE ON ISOLATED WORKING DIABETIC RAT-HEART
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DOI：
10.1152/ajpheart.1991.261.4.h1053
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发表时间：
1991-10-01
影响因子：
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通讯作者：
MCNEILL, JH
中科院分区：
文献类型：
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作者：
NICHOLL, TA;LOPASCHUK, GD;MCNEILL, JH
众所周知，患有糖尿病的人类和动物都会出现与动脉粥样硬化无关的心脏功能障碍。病因很复杂，涉及许多不同的过程，其中之一可能是糖尿病心脏的脂肪酸利用增加和/或伴随的葡萄糖利用减少。我们比较了对照组和 6 周链脲佐菌素 (STZ) 诱导的糖尿病离体工作大鼠心脏，通过降低心率 (HR)、心率峰值收缩压乘积 (HR.PSP)、左心室发展压 (LVDP) 和压力上升率 (+dP/dt) 评估，能够证明糖尿病患者的心脏功能障碍。与年龄匹配的对照组相比，糖尿病患者心功能下降的同时还包括高血糖、高脂血症和体重增加减少。将 1.2 mM 棕榈酸酯形式的游离脂肪酸添加到分离的工作心脏灌注液中，除了对糖尿病心脏的 +dP/dt 产生抑制作用外，对对照或糖尿病心脏功能没有影响。但用含棕榈酸盐的灌注液加上葡萄糖氧化刺激剂二氯乙酸酯（DCA）进行灌注的糖尿病心脏显示出功能的显着改善。在 DCA 存在下灌注的糖尿病心脏中，自发跳动心脏中的 HR 和 HR.PSP 以及起搏心脏中的 LVDP 和 +dP/dt 全部恢复以控制心脏值。在所有灌注条件下，磷酸肌酸和 ATP 水平相似，因此消除了能量储存作为心脏功能的限制因素。结果表明 DCA 可以显着逆转糖尿病心脏功能抑制。因此，糖尿病心脏中的葡萄糖氧化抑制可能是导致心功能障碍的重要因素。
It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction.