Fleisig Ani J, Verrier Edward D
Division of Cardiothoracic Surgery, University of Washington, 1959 NE Pacific Seattle, Washington, WA 98195, USA.
Expert Opin Biol Ther. 2005 Jun;5(6):833-9. doi: 10.1517/14712598.5.6.833.
Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab (Alexion Pharmaceuticals, Inc., Cheshire, CT, USA) is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms. Prospective, randomised, double-blind, placebo-controlled trials using pexelizumab during percutaneous coronary intervention following acute myocardial infarction (AMI), or in patients undergoing coronary artery bypass graft (CABG) with CPB, have demonstrated a reduction in morbidity and mortality. Thus, pexelizumab represents a promising therapeutic option with sustained benefit both in AMI and during CABG with CPB.
急性心肌梗死以及体外循环心脏手术期间的心肌损伤和功能障碍与不良的全身炎症反应相关,补体级联反应在其中起主要作用。在动物模型中,已发现抑制C5可显著减小心肌梗死面积,并减少细胞坏死和凋亡。沛西利珠单抗(美国康涅狄格州柴郡Alexion制药公司)是一种人源化单克隆单链抗体片段,可抑制C5,从而阻止其裂解为活性形式。在急性心肌梗死(AMI)后经皮冠状动脉介入治疗期间或在接受体外循环冠状动脉搭桥术(CABG)的患者中使用沛西利珠单抗进行的前瞻性、随机、双盲、安慰剂对照试验表明,发病率和死亡率有所降低。因此,沛西利珠单抗是一种有前景的治疗选择,在AMI和体外循环CABG期间均具有持续的益处。