Total ischemia III: Effect of inhibition of anaerobic glycolysis.
Total ischemia III: Effect of inhibition of anaerobic glycolysis.
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完全缺血III：无氧糖酵解的抑制作用。
DOI：
10.1016/0022-2828(89)90836-5
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发表时间：
1989
影响因子：
5
通讯作者：
Schaper,J
中科院分区：
文献类型：
--
作者：
Jennings,RB;Reimer,KA;SteenbergenJr,C;Schaper,J
研究了碘乙酸钠（IAA）抑制糖酵解对犬左心室全缺血变化的影响。取麻醉犬的心脏，灌注左冠状动脉旋支（LCC）和前降支（LAD），使LCC区暴露于48 μmol IAA（约1.5 μmol/g wet wt）。同一心脏的LAD区域作为未治疗的对照心肌。然后将心脏置于37℃的体外完全缺血状态。在对照区和iaa处理区研究了代谢物、超微结构以及培养的心脏薄片维持体积和离子梯度的能力。在iaa处理的心肌中，ATP仅在缺血4-5分钟内就消耗到对照组3-4%的水平，而在未处理的心肌中，类似的消耗需要90分钟的全缺血。这些低水平的ATP与明显的收缩严密性有关。IAA处理区域ATP的耗竭伴随着组织中腺苷水平的显著增加，在僵硬开始时（约5分钟）；此时，多达50%的腺嘌呤核苷酸库（ΣAd）以腺苷的形式存在。相比之下，肌苷是对照心肌5分钟时主要的分解代谢物，仅占ΣAd池的16%。因此，IAA预处理可大大加快完全缺血心肌中ΣAd池的消耗速度。乳酸，主要的糖酵解中间体，在完全缺血组织中积累，在iaa处理的心脏中没有形成。此外，IAA处理并没有加速中毒肌细胞超微结构致死性损伤的发生。因此，在没有发生乳酸积累的情况下，与未处理的组织相比，完全缺血的肌细胞耐受非常低水平的高能磷酸盐的时间更长，然后才出现细胞死亡的超微结构迹象。结果表明，明显的ATP耗竭并不一定会引起肌上皮的迅速破坏。
The effect of inhibition of glycolysis with sodium iodoacetate (IAA) on the changes induced by total ischemia was studied in canine left ventricle. Hearts were excised from phenobarbital anesthetized dogs and the circumflex (LCC) and anterior descending (LAD) branches of the left coronary artery were perfused in order to expose the LCC region to 48 μmol of IAA (about 1·5 μmol/g wet wt). The LAD regions of the same hearts served as untreated control myocardium. Hearts then were subjected to total ischemiain vitroat 37°C. Metabolites, ultrastructure, and the capacity of thin incubated slices of heart to maintain volume and ion gradients were studied in the control and IAA-treated regions. Depletion of ATP to levels of 3–4% of control occurred in only 4–5 min of ischemia in the IAA-treated myocardium, but similar depletion required 90 min of total ischemia in untreated myocardium. These low levels of ATP were associated with marked contracture-rigor. Depletion of ATP in the IAA treated region was accompanied by a marked increase in adenosine levels in the tissue at the onset of rigor (∼5 min); at this time, as much as 50% of the adenine nucleotide pool (ΣAd) was in the form of adenosine. In contrast, inosine was the predominant catabolite at 5 min in control myocardium, and only composed 16% of the ΣAd pool. Thus, pretreatment with IAA produced an enormous acceleration in the rate at which the ΣAd pool was consumed in totally ischemic myocardium. Lactate, the principal glycolytic intermediate which accumulates in totally ischemic tissue, was not formed in the IAA-treated heart. Moreover, IAA treatment did not accelerate the rate at which ultrastructural evidence of lethal injury developed in the poisoned myocytes. Thus, in a setting in which lactate accumulation did not occur, totally ischemic myocytes tolerated a very low level of high energy phosphate for a longer period of time than did untreated tissue before ultrastructural signs of cell death developed. The results indicate that marked ATP depletion,pe se, does not necessarity cause prompt sarcolemmal disruption.