Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Basic Clin Pharmacol Toxicol. 2011 Apr;108(4):256-62. doi: 10.1111/j.1742-7843.2010.00651.x. Epub 2010 Dec 8.
Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.
缺血再灌注损伤是体外循环心脏手术后发生的一种病理生理事件。这种临床事件与心房组织中氧化和炎症损伤的诱导有关。在这里,我们测试了联合ω-3 多不饱和脂肪酸(n-3 PUFA)-抗氧化维生素方案治疗是否可以减轻氧化和炎症性心脏组织损伤。这项试验将 95 名男女患者分为 n-3 PUFA(2 克/天)补充组或匹配的安慰剂组,在体外循环手术前 7 天开始补充。抗氧化维生素 C(1 克/天)和 E(400 IU/天)或安慰剂从手术前 2 天开始添加,直到出院。在干预期间采集血液和心房组织样本。在心房组织中测定还原/氧化型谷胱甘肽(GSH/GSSG)比值、丙二醛(MDA)和蛋白质羰基化。血液中的白细胞计数和高敏 C 反应蛋白(hs-CRP)加上心房组织中的核因子(NF)-κB 激活用于炎症评估。补充组的脂质过氧化和蛋白质羰基化分别降低了 27.5%和 24%(p < 0.01)。与安慰剂相比,补充组的 GSH/GSSG 比值高 38.1%(p < 0.01)。补充组的白细胞计数和血清 hs-CRP 水平在整个方案中均明显降低(p < 0.01)。与安慰剂组相比,补充组心房组织 NF-κB DNA 激活降低了 22.5%(p < 0.05)。这里提出的联合 n-3 PUFA-抗氧化维生素方案治疗可降低体外循环心脏手术后患者的氧化应激和炎症生物标志物。