Mazzone A, Pasotti D, Mazzucchelli I, Fossati G, Ricevuti G
Dipartimento di Medicina Interna e Terapia Medica, Università, IRCCS Policlinico San Matteo, Pavia.
Recenti Prog Med. 1994 Jul-Aug;85(7-8):397-406.
Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Granulocytes can release a variety of mediators tissue injury and synergize with these different mediators, cytokines and other cells resulting in amplification of neutrophil stimulation and rising to additional products with enhanced endothelial injury. Free radicals released by PMNs during ischemia or reperfusion produce deleterious effects on cell membranes, endothelial cells and myocardium. Experience in humans shows the modification of PMNs function in angina and during myocardial ischemia: upon reperfusion PMNs accumulate and produce an inflammatory response leading to endothelial injury. Rabbit derived antiserum dependent-reduction of circulating PMNs in the dog or using monoclonal antibody anti-CD11b/CD18 of PMNs resulted in smaller myocardial infarction. Another aspect of PMNs function is related to leukotriene C4 release; the vasoconstrictor effect of this leukotriene on coronary arteries is synergistic with that induced by platelet-released thromboxane A2, and the decrease in coronary flow produced by the combination of both substances is greater than the sum of changes caused by the two eicosanoids separately administered. The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in the pathophysiology of myocardial injury due to regional ischemia and reperfusion is an area of intense investigation. This overview will not attempt to be exhaustive. Experimental and clinical studies to elucidate these events should not only provide insight into acute and chronic pathologic tissue damage, but may also lead to the identification of important new targets of pharmacologic intervention.
近期研究表明，粒细胞（多形核白细胞）在急性和慢性心肌缺血的发病机制以及心肌损伤的扩展中发挥作用。粒细胞可释放多种介导组织损伤的介质，并与这些不同的介质、细胞因子及其他细胞协同作用，导致中性粒细胞刺激的放大，并产生更多具有增强内皮损伤作用的产物。缺血或再灌注期间多形核白细胞释放的自由基对细胞膜、内皮细胞和心肌产生有害影响。人体研究显示了心绞痛和心肌缺血期间多形核白细胞功能的改变：再灌注时多形核白细胞聚集并产生炎症反应，导致内皮损伤。在犬体内使用兔源性抗血清降低循环中的多形核白细胞数量，或使用抗多形核白细胞CD11b/CD18单克隆抗体，均可使心肌梗死面积减小。多形核白细胞功能的另一个方面与白三烯C4的释放有关；这种白三烯对冠状动脉的血管收缩作用与血小板释放的血栓素A2诱导的作用协同，两种物质共同作用导致的冠状动脉血流减少大于分别给予这两种类花生酸所引起变化的总和。白细胞、氧自由基、白三烯和粒细胞酶在局部缺血和再灌注所致心肌损伤病理生理学中的潜在作用是一个深入研究的领域。本综述并不试图详尽无遗。阐明这些事件的实验和临床研究不仅应能深入了解急性和慢性病理性组织损伤，还可能有助于确定重要的新药物干预靶点。
