Rodrigo Ramón, Cereceda Mauricio, Castillo Rodrigo, Asenjo René, Zamorano Jaime, Araya Julia, Castillo-Koch Rodrigo, Espinoza Juan, Larraín Ernesto
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Pharmacol Ther. 2008 Apr;118(1):104-27. doi: 10.1016/j.pharmthera.2008.01.005. Epub 2008 Feb 15.
Atrial fibrillation is the most common complication of cardiac surgical procedures performed with cardiopulmonary bypass. It contributes to increased hospital length of stay and treatment costs. At present, preventive strategies offer only suboptimal benefits, despite improvements in anesthesia, surgical technique, and medical therapy. The pathogenesis of postoperative atrial fibrillation is considered to be multifactorial. However oxidative stress is a major contributory factor representing the unavoidable consequences of ischemia/reperfusion cycle occurring in this setting. Considerable evidence suggests the involvement of reactive oxygen species (ROS) in the pathogenic mechanism of this arrhythmia. Interestingly, the deleterious consequences of high ROS exposure, such as inflammation, cell death (apoptosis/necrosis) or fibrosis, may be abrogated by a myocardial preconditioning process caused by previous exposure to moderate ROS concentration known to trigger survival response mechanisms. The latter condition may be created by n-3 PUFA supplementation that could give rise to an adaptive response characterized by increased expression of myocardial antioxidant enzymes and/or anti-apoptotic pathways. In addition, a further reinforcement of myocardial antioxidant defenses could be obtained through vitamins C and E supplementation, an intervention also known to diminish enzymatic ROS production. Based on this paradigm, this review presents clinical and experimental evidence supporting the pathophysiological and molecular basis for a novel therapeutic approach aimed to diminish the incidence of postoperative atrial fibrillation through a non-hypoxic preconditioning plus a reinforcement of the antioxidant defense system in the myocardial tissue.
心房颤动是体外循环心脏手术最常见的并发症。它会导致住院时间延长和治疗费用增加。目前，尽管在麻醉、手术技术和药物治疗方面有所改进，但预防策略的效果仍不尽人意。术后心房颤动的发病机制被认为是多因素的。然而，氧化应激是一个主要的促成因素，代表了在此情况下发生的缺血/再灌注循环不可避免的后果。大量证据表明活性氧（ROS）参与了这种心律失常的发病机制。有趣的是，高ROS暴露的有害后果，如炎症、细胞死亡（凋亡/坏死）或纤维化，可能会被先前暴露于已知能触发生存反应机制的适度ROS浓度所引起的心肌预处理过程所消除。后一种情况可以通过补充n-3多不饱和脂肪酸来实现，这可能会引发一种适应性反应，其特征是心肌抗氧化酶和/或抗凋亡途径的表达增加。此外，通过补充维生素C和E可以进一步增强心肌抗氧化防御能力，这种干预也已知能减少酶促ROS的产生。基于这一模式，本综述提供了临床和实验证据，支持一种新的治疗方法的病理生理和分子基础，该方法旨在通过非缺氧预处理和增强心肌组织中的抗氧化防御系统来降低术后心房颤动的发生率。
