Opie L H
Jpn Circ J. 1978 Nov;42(11):1223-47. doi: 10.1253/jcj.42.1223.
Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
缺氧已与缺血相比较。氧或血流的突然恢复可能会加速心脏损伤。在缺血期间，由于乳酸和质子在磷酸果糖激酶和甘油醛-3-磷酸脱氢酶水平的积累，缺氧对糖酵解的刺激（巴斯德效应）受到抑制。无氧糖酵解产生乳酸和ATP；ATP的分解产生质子。在局部缺血时发生的部分呼吸过程中，持续产生的二氧化碳是导致细胞内酸中毒的一个因素；线粒体ATP在通过持续呼吸形成时，最终分解也会产生质子。有氧糖酵解的终产物（丙酮酸和NADH）通过苹果酸-天冬氨酸循环和丙酮酸脱氢酶活性被转运到线粒体中。腺嘌呤核苷酸转移酶活性通常将线粒体产生的ATP转运到细胞质中，但在缺血时（或在用高循环游离脂肪酸灌注期间）酰基辅酶A积累以抑制该转移酶。线粒体肌酸激酶被认为将向外转运的ATP转化为可透过线粒体外膜的磷酸肌酸。ATP的进一步分隔可能由其他肌酸激酶同工酶或与细胞膜有关。糖原分解-肌浆网复合体将糖原池与肌浆网连接起来。环磷酸腺苷（cAMP）可能在动作电位平台期调节钙进入细胞，并通过使受磷蛋白磷酸化促进肌浆网摄取钙。后者促进钙转运ATP酶的活性。钙和cAMP也可能在收缩蛋白水平相互作用，其中cAMP使肌钙蛋白磷酸化。环磷酸鸟苷（cGMP）通常具有与cAMP相反的作用，并且在青蛙心动周期中发生与cAMP相反的变化。目前有理由推测，肾上腺素或胆碱能药物对心肌的生理作用分别由cAMP或cGMP介导，但这一假说仍缺乏确凿的支持。冠状动脉结扎后组织cAMP与心室颤动之间存在关联，并且通过对大鼠心脏心室颤动阈值的研究获得了cAMP在促进心律失常中起作用的直接证据。然而，还有其他机制，首先涉及底物对动作电位持续时间的影响，其次涉及快速通道，它们也可导致恶性心律失常的发生。
