Burton K P, Buja L M, Sen A, Willerson J T, Chien K R
Am J Pathol. 1986 Aug;124(2):238-45.
Alterations in triacylglycerol and phospholipid metabolism are known to occur during the evolution of myocardial ischemic injury. The purpose of this study was to explore potential relationships between the accumulation of arachidonic acid and other fatty acids, the accumulation of triacylglycerol, and the progression of myocardial injury. Measurements of the fatty acid levels in triacylglycerol, unesterified fatty acids, and calcium content were correlated with myocardial function during ischemia and ischemia with reflow in an isolated perfused rat heart preparation. After 10 minutes of ischemia in this model, myocardial dysfunction was reversible, with recovery of left ventricular +dP/dt to 82.0% +/- 4.8% of control values upon reperfusion. Hearts did not recover with reperfusion after 30 minutes of ischemia and displayed a significant increase in tissue calcium content. A significant, nearly threefold increase in the arachidonic acid content of triacylglycerol was found after 10 minutes of ischemia and continued to increase with longer periods of ischemia and reflow. Other fatty acids also showed increased levels in triacylglycerol. The time course of accumulation of unesterified arachidonic acid paralleled the loss of myocardial function. Levels of free arachidonic acid were (in nanomoles per gram wet weight) 11.1 +/- 2.1 (SEM) for control hearts, 17.3 +/- 1.9 after 10 minutes of ischemia, and 38.4 +/- 2.5 after 30 minutes of ischemia. Increases in other free fatty acids contributed to a significant increase in total free fatty acid accumulation after 30 minutes of ischemia. Thus, the content of arachidonic and other fatty acids in triacylglycerol was found to increase early during ischemia, and a major increase in free arachidonic and other unesterified fatty acids occurred after a longer period of ischemia. These findings are consistent with an initial reincorporation of free fatty acids into triacylglycerol after release from membrane phospholipids, suggesting that membrane fatty acids may be a major source of triacylglycerol that accumulates in ischemic myocardium. In addition, these results suggest that a major increase in free fatty acids during ischemia and ischemia with reflow correlates temporally with the development of severe contractile dysfunction and accumulation of calcium in the heart.
已知在心肌缺血性损伤的发展过程中会发生三酰甘油和磷脂代谢的改变。本研究的目的是探讨花生四烯酸和其他脂肪酸的积累、三酰甘油的积累与心肌损伤进展之间的潜在关系。在离体灌注大鼠心脏标本中，测量三酰甘油中的脂肪酸水平、未酯化脂肪酸和钙含量，并将其与缺血期间以及缺血再灌注期间的心肌功能相关联。在此模型中，缺血10分钟后，心肌功能障碍是可逆的，再灌注时左心室 +dP/dt 恢复至对照值的82.0%±4.8%。缺血30分钟后心脏再灌注未能恢复，且组织钙含量显著增加。缺血10分钟后，三酰甘油中的花生四烯酸含量显著增加近三倍，并随着缺血和再灌注时间延长而持续增加。其他脂肪酸在三酰甘油中的水平也有所升高。未酯化花生四烯酸的积累时间进程与心肌功能丧失平行。对照心脏的游离花生四烯酸水平（以每克湿重纳摩尔计）为11.1±2.1（标准误），缺血10分钟后为17.3±1.9，缺血30分钟后为38.4±2.5。缺血30分钟后，其他游离脂肪酸的增加导致总游离脂肪酸积累显著增加。因此，发现缺血早期三酰甘油中花生四烯酸和其他脂肪酸的含量增加，而在较长时间缺血后，游离花生四烯酸和其他未酯化脂肪酸大幅增加。这些发现与游离脂肪酸从膜磷脂释放后最初重新掺入三酰甘油一致，表明膜脂肪酸可能是缺血心肌中积累的三酰甘油的主要来源。此外，这些结果表明，缺血期间以及缺血再灌注期间游离脂肪酸的大幅增加在时间上与严重收缩功能障碍的发展以及心脏中钙的积累相关。
