Development of cell injury in sustained acute ischemia.
Development of cell injury in sustained acute ischemia.
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发表时间：
1990
期刊：
影响因子：
37.8
通讯作者：
Robert B. Jennings;Charles E. Murry;Charles Steenbergen;K. Reimer
中科院分区：
文献类型：
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作者：
Robert B. Jennings;Charles E. Murry;Charles Steenbergen;K. Reimer
在哺乳动物心脏中，通过阻塞冠状动脉的主要分支而突然诱导缺血，引发一系列事件，最终导致明显缺血的心肌细胞死亡。这些变化开始于闭塞的8-10秒内，包括1）有氧代谢的停止，2）磷酸肌酸的消耗，3）无氧糖酵解（AG）的开始，和4）缺血组织中缺氧代谢产物的积累。功能缺陷同时出现，包括收缩活动抑制和心电图变化。缺血心肌细胞对能量的需求超过了AG可能提供的高能磷酸盐（约P）;因此，心肌细胞腺苷二磷酸增加，腺苷酸激酶被激活以捕获腺苷二磷酸的约P键。腺苷一磷酸是这种反应的产物;它积累并逐渐降解为核苷和碱基，从肌细胞中丢失。在缺血40-60分钟后，短期代谢变化的发展速度减慢，此时大多数严重缺血的肌细胞受到不可逆的损伤。在损伤组织的不可逆阶段的早期，其特征如下：1）极低的近似P含量（磷酸肌酸少于对照的1-2%，三磷酸腺苷少于对照的10%），2）主要由单磷酸腺苷组成的降低的腺嘌呤核苷酸库，3）AG的实际停止，4）低pH和低糖原含量，5）高肌苷和次黄嘌呤含量，6）主要由乳酸盐组成的渗透压负荷显著增加，和7）特征性超微结构变化，包括细胞肿胀和广泛的线粒体和显著的肌膜损伤的证据。肌膜破坏是我们假设导致不可逆性的特征;然而，其发病机制尚不清楚。
Sudden induction of ischemia by occlusion of a major branch of a coronary artery in mammalian heart sets into motion a series of events that culminates in the death of markedly ischemic myocytes. The changes begin within 8-10 seconds of occlusion and include 1) cessation of aerobic metabolism, 2) depletion of creatine phosphate, 3) onset of anaerobic glycolysis (AG), and 4) accumulation of products of anoxic metabolism in the ischemic tissue. Functional defects appear simultaneously, including depressed contractile activity and electrocardiographic changes. The demand of the ischemic myocytes for energy exceeds the supply of high-energy phosphate (approximately P) possible from AG; as a consequence, myocyte adenosine diphosphate increases, and adenylate kinase is activated to capture the approximately P bond of adenosine diphosphate. Adenosine monophosphate is a product of this reaction; it accumulates and is progressively degraded to nucleosides and bases that are lost from the myocyte. The pace of development of the short-term metabolic changes slows after 40-60 minutes of ischemia, at which time most of the severely ischemic myocytes are irreversibly injured. Early in the irreversible phase of injury tissue is characterized as follows by: 1) very low approximately P content (creatine phosphate less than 1-2% and adenosine triphosphate less than 10% of control), 2) a depressed adenine nucleotide pool that consists principally of adenosine monophosphate, 3) virtual cessation of AG, 4) low pH and low glycogen content, 5) high inosine and hypoxanthine contents, 6) a markedly increased osmolar load consisting chiefly of lactate, and 7) characteristic ultrastructural changes including cell swelling and evidence of generalized mitochondrial and marked sarcolemmal damage. Sarcolemmal disruption is the feature that we hypothesize causes irreversibility; however, its pathogenesis is unknown.