ROLE OF GLYCOLYTIC PRODUCTS IN DAMAGE TO ISCHEMIC MYOCARDIUM - DISSOCIATION OF ADENOSINE-TRIPHOSPHATE LEVELS AND RECOVERY OF FUNCTION OF REPERFUSED ISCHEMIC HEARTS
ROLE OF GLYCOLYTIC PRODUCTS IN DAMAGE TO ISCHEMIC MYOCARDIUM - DISSOCIATION OF ADENOSINE-TRIPHOSPHATE LEVELS AND RECOVERY OF FUNCTION OF REPERFUSED ISCHEMIC HEARTS
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DOI：
10.1161/01.res.55.6.816
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发表时间：
1984-01-01
影响因子：
20.1
通讯作者：
GROTYOHANN, LW
中科院分区：
文献类型：
--
作者：
NEELY, JR;GROTYOHANN, LW
在大鼠心脏灌流模型上研究了缺血心肌不可逆损伤的机制。糖酵解产物的积累和细胞外Ca的增加加速了收缩功能从可逆性损伤到不可逆性损伤的过渡时间。这两种效应在很大程度上与组织中的腺嘌呤核苷酸水平无关。冠状动脉流量为零，钙浓度为1.25 mM时，缺血30分钟后再灌注心脏恢复心室功能的能力下降，与缺血期间糖酵解产物的积累（由组织乳酸盐估计）直接相关。通过在缺氧、高冠状动脉流量条件下预灌注心脏0、10或15分钟以在缺血前耗尽组织糖原，并通过在缺血期间将乳酸盐添加回这些心脏的灌注液中，来改变缺血期间乳酸盐积累的程度。心室功能的恢复与缺血期间的组织乳酸呈负相关，范围为28%至92%，即使残留ATP的组织水平几乎没有变化。增加细胞外Ca加速了不可逆损伤的发生时间，而残留ATP水平几乎没有变化。在任何给定的Ca浓度下，心脏恢复心室功能的能力的时间依赖性下降也在很大程度上与ATP水平无关。厌氧糖酵解产物（乳酸盐、氢离子或NADH）在心脏缺血性损伤中的主要作用与组织腺嘌呤核苷酸的丢失无关。在零或低血流缺血时，这种效应可能在腺嘌呤核苷酸降低到极低水平之前对心肌造成不可逆的损伤。
The mechanism of irreversible damage to ischemic myocardium was investigated in the perfused rat heart. The time of transition from reversible to irreversible damage to contractile function was accelerated by accumulation of glycolytic products and increases in extracellular Ca. Both of these effects were largely independent of adenine nucleotide levels in the tissue. With zero coronary flow and 1.25 mM Ca the decrease in ability of the heart to recover ventricular function with reperfusion after 30 min of ischemia was directly correlated with accumulation of glycolytic products (as estimated by tissue lactate) during ischemia. The extent of lactate accumulation during ischemia was varied by preperfusing the hearts for 0, 10, or 15 min under anoxic, high coronary flow conditions to deplete tissue glycogen prior to ischemia, and by adding lactate back to the perfusate of these hearts during the ischemic period. Recovery of ventricular function was inversely related to tissue lactate during ischemia and varied from 28 to 92%, even though there was little or no change in tissue levels of residual ATP. Increasing extracellular Ca accelerated the time of onset of irreversible damage with little or no change in residual ATP levels. At any given Ca concentration, the time-dependent declines in the ability of the heart to recover ventricular function was also largely independent of ATP levels. A major role of anaerobic glycolytic products (lactate, hydrogen ion, or NADH) in ischemic damage to the heart that is unrelated to loss of tissue adenine nucleotides is suggested. With zero or low flow ischemia, this effect may result in irreversible damage to the myocardium before adenine nucleotides are reduced to critically low levels.