Hearse D J
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital London, UK.
Cardiovasc Drugs Ther. 1990 Aug;4 Suppl 4:767-76. doi: 10.1007/BF00051274.
Much of the damage arising during ischemia and reperfusion can be attributed to the consequences of flow deprivation. However, while reperfusion is a prerequisite for the survival of tissue, it may have an injurious component, which, if counteracted, might enhance postischemic recovery. The complex and dynamic changes that occur during ischemia in the diseased human heart are difficult to model in experimental preparations. As a consequence, much remains to be learned about the identity and manipulability of cellular changes leading to irreversible injury. Although the subject of most studies, injury to the myocyte may not be the primary determinant of tissue injury and changes in the endothelium or vascular smooth muscle may play an important role. Once critical ischemia-induced cellular changes have been identified, interventions can be developed to delay their progression such that at the time of reperfusion more cells are potentially salvable. Suboptimal reperfusion may limit the recovery of the tissue through the induction of "reperfusion injury." Much controversy surrounds the importance and even the existence of this phenomenon. It is proposed that reperfusion injury may express itself in four distinct forms: a) reperfusion-induced arrhythmias, which are potentially lethal (but preventable or reversible) events occurring in otherwise viable tissue; b) myocardial stunning, which is expressed as prolonged (but eventually fully reversible) contractile and metabolic dysfunction; c) the induction of lethal injury in tissue that was potentially viable in the moments before reperfusion; d) accelerated necrosis in tissue that is already irreversibly injured (the "oxygen paradox"). All but the third of these categories has been shown to exist experimentally and clinically, and can be advantageously manipulated. Although it is likely that lethal reperfusion injury also exists, there is as yet no definitive proof. Clarification of this issue is of considerable importance to those undergoing angioplasty or thrombolytic procedures.
缺血和再灌注期间产生的许多损伤可归因于血流阻断的后果。然而，尽管再灌注是组织存活的先决条件，但它可能具有损伤性成分，如果能够对抗这种成分，可能会增强缺血后的恢复。患病人类心脏在缺血期间发生的复杂动态变化很难在实验制剂中模拟。因此，关于导致不可逆损伤的细胞变化的特征和可操控性，仍有许多有待了解。尽管心肌细胞损伤是大多数研究的主题，但它可能不是组织损伤的主要决定因素，内皮或血管平滑肌的变化可能起重要作用。一旦确定了关键的缺血诱导细胞变化，就可以开发干预措施来延缓其进展，以便在再灌注时更多细胞有可能被挽救。次优再灌注可能通过诱导“再灌注损伤”来限制组织的恢复。围绕这一现象的重要性甚至其存在，存在很多争议。有人提出，再灌注损伤可能以四种不同形式表现出来：a）再灌注诱导的心律失常，这是在原本存活的组织中发生的潜在致命（但可预防或可逆）事件；b）心肌顿抑，表现为延长（但最终完全可逆）的收缩和代谢功能障碍；c）在再灌注前片刻可能存活的组织中诱导致命损伤；d）在已经不可逆损伤的组织中加速坏死（“氧悖论”）。除了第三类之外，所有这些类别都已在实验和临床中得到证实，并且可以进行有益的操控。尽管可能也存在致命的再灌注损伤，但目前尚无确凿证据。对于接受血管成形术或溶栓手术的患者来说，澄清这个问题非常重要。
