Ansley David M, Raedschelders Koen, Chen David D Y, Choi Peter T
Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
Contemp Clin Trials. 2009 Jul;30(4):380-5. doi: 10.1016/j.cct.2009.03.004. Epub 2009 Mar 29.
Diabetes mellitus is a leading cause of death globally and results in significant morbidity and mortality following surgery. After cardiac surgery, diabetic patients are especially at risk for low cardiac output syndrome, which can quadruple the risk for postoperative death. Attempts to prevent low cardiac output syndrome have focused on increasing myocardial tolerance to ischemia (preconditioning), which involves the myocardial mitochondrial ATP-regulated K(ATP) channel, G-protein initiation, nitric oxide synthase, and protein kinase C. Unfortunately, the signal transduction pathways required for preconditioning are corrupted in diabetes. Effective antioxidant intervention during ischemia-reperfusion appears important for preserving myocardial function; thus, alleviating oxidant-mediated post-ischemic injury by increasing antioxidant defenses (cardioprotection) is an alternative to preconditioning. Our previous work suggests that propofol (2,6-diisopropylphenol), an intravenous anesthetic with antioxidant potential, may confer cardioprotection. In this paper, we describe the rationale and methodology of the Pro-TECT II Study, a Phase II randomized controlled trial designed to explore the relationships of biomarkers of oxidative or nitrosative stress in diabetes, to determine the effect of propofol cardioprotection to counteract these effects in patients undergoing elective primary coronary bypass graft surgery with cardiopulmonary bypass, and to provide feasibility and sample size data needed to conduct Phase III trials.
糖尿病是全球主要的死亡原因之一，并且在手术后会导致显著的发病率和死亡率。心脏手术后，糖尿病患者尤其易患低心排血量综合征，这会使术后死亡风险增加四倍。预防低心排血量综合征的尝试主要集中在提高心肌对缺血的耐受性（预处理），这涉及心肌线粒体ATP调节的钾离子通道（KATP）、G蛋白启动、一氧化氮合酶和蛋白激酶C。不幸的是，糖尿病会破坏预处理所需的信号转导通路。缺血再灌注期间有效的抗氧化干预对于保护心肌功能似乎很重要；因此，通过增强抗氧化防御（心脏保护）来减轻氧化应激介导的缺血后损伤是预处理的一种替代方法。我们之前的研究表明，丙泊酚（2,6 - 二异丙基苯酚），一种具有抗氧化潜力的静脉麻醉剂，可能具有心脏保护作用。在本文中，我们描述了Pro - TECT II研究的基本原理和方法，这是一项II期随机对照试验，旨在探索糖尿病患者氧化或亚硝化应激生物标志物之间的关系，确定丙泊酚心脏保护作用对接受择期冠状动脉搭桥手术并行体外循环患者这些效应的抵消作用，并提供开展III期试验所需的可行性和样本量数据。
