MICA: Developmental clinical studies- Effect of elafin on myocardial injury and inflammation in coronary artery bypass surgery

心肌细胞在血流中断（心肌缺血）后容易受到损伤和死亡。冠状动脉搭桥术中发生的轻度损伤可以使用敏感的血液标志物（肌钙蛋白）来测量，为研究可能减少缺血性损伤的药物提供了有益的模型。中性粒细胞是循环的血细胞，通过释放破坏性酶（弹性酶）导致缺血性损伤。人体产生一种叫做elafin的蛋白质，可以减少中性粒细胞弹性蛋白酶的损伤。来自不同国际中心的广泛临床前工作表明，elafin在以中性粒细胞介导的损伤为特征的动脉和心脏疾病中具有治疗作用。我们认为，对接受搭桥手术的患者给予elafin将减少中性粒细胞介导的心肌损伤和术后炎症活动的增加。缺血期间心肌损伤的程度决定了临床结果。没有治疗方法可用于解决中性粒细胞介导的心肌损伤和药物的开发，以减少这提供了实质性的临床效益。

Heart muscle cells are susceptible to injury and death following interruption of blood flow (myocardial ischaemia). A mild form of injury occurs during coronary artery bypass surgey and can be measured using a sensitive blood marker (troponin) providing a helpful model to study drugs that may reduce ischaemic injury. Neutrophils are circulating blood cells that contribute to ischaemic injury by releasing destructive enzymes (elastases). Humans produce a protein called elafin that reduces neutrophil elastase injury. Extensive preclinical work from different international centres indicates that elafin has a therapeutic role in diseases of the arteries and heart characterised by neutrophil mediated injury. We believe that administering elafin to patients undergoing bypass surgery will reduce neutrophil mediated myocardial injury and the rise in post-operative inflammatory activity. The degree of heart muscle damage occurring during ischaemia determines clinical outcomes. No therapies are available to address neutrophil mediated heart muscle injury and development of a drug to reduce this offers substantial clinical benefit.