Janero D R
NitroMed, Inc., Boston, MA 02118, USA.
Crit Rev Food Sci Nutr. 1995 Jan;35(1-2):65-81. doi: 10.1080/10408399509527688.
The disease state of myocardial ischemia results from a hypoperfusion-induced insufficiency of heart-muscle oxidative metabolism due to inadequate coronary circulation. Myocardial ischemia is an important, lifespan-limiting medical problem and a major economic health-care concern. Reperfusion, although avidly pursued in the clinic as essential to the ultimate survival of acutely ischemic heart muscle, may itself carry an injury component. Cardiac reperfusion injury appears to reflect, at least in part, an oxidant burden established upon reoxygenation of ischemic myocardium. Laboratory evidence demonstrates that oxidative stress to the heart-muscle cell (cardiomyocyte) can elicit the three known types of ischemia-reperfusion injury that directly affect the myocardium: arrhythmia, stunning, and infarction. The limited clinical occurrence of serious reperfusion arrhythmias has restricted the importance of antioxidants as antiarrhythmic agents against this form of myocardial ischemia-reperfusion damage. Despite the utmost clinical significance of lethal cardiomyocyte injury as a negative prognostic indicator for the ischemic heart-disease patient, inconsistent results of antioxidant interventions in reducing infarct size have somewhat tempered interest in antioxidant infarct trials. By contrast, the negative clinical consequences of stunning may indeed be preventable by utilizing antioxidants to help restore postischemic cardiac pump function. Several as yet unanswered questions remain regarding oxidative stress in the reperfused heart, its significance to cardiomyocyte damage, and its ability to elicit specific postischemic myocardial derangements. Targeted mechanistic studies are required to address these questions and to define the pathogenic role of oxidative stress (and, hence, the therapeutic potential of antioxidant intervention) in myocardial ischemia-reperfusion injury. The overall aim of current research in this area is to enable the cardiac surgeon/cardiologist to advance beyond the largely palliative drugs now available for management of the coronary heart-disease patient and attack directly the pathogenic determinants of heart-muscle ischemia-reperfusion injury. Optimal use of antioxidants may help address this important medical need.
心肌缺血的疾病状态是由于冠状动脉循环不足导致灌注不足引起的心肌氧化代谢功能不全所致。心肌缺血是一个重要的、限制寿命的医学问题，也是医疗保健领域的一个主要经济问题。再灌注虽然在临床上被积极追求，因为它对急性缺血心肌的最终存活至关重要，但它本身可能带有损伤成分。心脏再灌注损伤似乎至少部分反映了缺血心肌再氧合时产生的氧化负担。实验室证据表明，对心肌细胞的氧化应激可引发直接影响心肌的三种已知类型的缺血再灌注损伤：心律失常、心肌顿抑和梗死。严重再灌注心律失常在临床上的发生率有限，这限制了抗氧化剂作为抗心律失常药物对抗这种形式的心肌缺血再灌注损伤的重要性。尽管致命的心肌细胞损伤作为缺血性心脏病患者的负面预后指标具有极其重要的临床意义，但抗氧化剂干预在减少梗死面积方面的结果不一致，这在一定程度上降低了人们对抗氧化剂梗死试验的兴趣。相比之下，通过使用抗氧化剂帮助恢复缺血后心脏泵功能，心肌顿抑的负面临床后果可能确实是可以预防的。关于再灌注心脏中的氧化应激、其对心肌细胞损伤的意义以及引发特定缺血后心肌紊乱的能力，仍有几个尚未得到解答的问题。需要有针对性的机制研究来解决这些问题，并确定氧化应激在心肌缺血再灌注损伤中的致病作用（以及因此抗氧化剂干预的治疗潜力）。该领域当前研究的总体目标是使心脏外科医生/心脏病专家能够超越目前用于治疗冠心病患者的主要是姑息性的药物，直接攻击心肌缺血再灌注损伤的致病决定因素。最佳使用抗氧化剂可能有助于满足这一重要的医疗需求。
