Impaired mitochondrial response to simulated ischemic injury as a predictor of the development of atrial fibrillation after cardiac surgery: In vitro study in human myocardium
Impaired mitochondrial response to simulated ischemic injury as a predictor of the development of atrial fibrillation after cardiac surgery: In vitro study in human myocardium
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DOI：
10.1016/j.jtcvs.2004.03.058
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发表时间：
2005-01-01
影响因子：
6
通讯作者：
Schwalb, H
中科院分区：
文献类型：
--
作者：
Ad, N;Schneider, A;Schwalb, H
目的：心脏手术后房颤的发生率为20%~40%，但其病理生理机制尚不清楚。最近的研究表明，先前存在的组织学标志物预示着术后房颤的发展。在这项前瞻性研究中，我们将重点放在线粒体功能障碍对缺血应激的反应，作为术后心房纤颤的潜在预测指标。方法：对50例择期心脏手术患者的右房小梁切片进行含氧葡萄糖磷酸盐缓冲液灌流。在稳定30min后，将切片暴露于模拟缺血90min(不含葡萄糖的含氮磷酸盐缓冲盐水溶液)中，然后进行90min的复氧(重新引入含氧溶液)。3-[4.5-二甲基噻唑-2-基]-2，5-二苯基四氮唑溴化法检测线粒体活力和反应。将模拟缺血后线粒体恢复量和28个可能的术后房颤危险因素进入单因素和多因素模型。结果：本组患者无死亡病例。术后发生房颤19例(38%)。有趣的是，术后有房颤和没有房颤的患者在基线(模拟缺血前)线粒体功能方面没有差别。术后心房颤动的一个独立预测因子是模拟缺血反应的线粒体功能障碍的程度，通过染色强度来衡量。结论：本研究首次确定了缺血反应的线粒体功能障碍与术后心房颤动之间的关联。这一发现提高了我们对术后心房颤动的病理生理学的理解，并最终可能导致我们确定选择性的术前或术后早期预防治疗的候选者。
Objective: Atrial fibrillation occurs in 20% to 40% of patients after cardiac surgery, but its pathophysiology remains unclear. Recent studies demonstrated preexisting histologic markers that portend the development of postoperative atrial fibrillation. In this prospective study, we focused on mitochondrial dysfunction in response to ischemic stress as a potential predictor for postoperative atrial fibrillation.Methods: Slices of right atrial trabeculae from 50 patients undergoing elective cardiac surgery were surperfused with oxygenated glucose-containing phosphate-buffered saline solution. After 30 minutes of stabilization, the sections were exposed to 90 minutes of simulated ischemia (nitrogenated phosphate-buffered saline solution without glucose) followed by 90 minutes of reoxygenation (reintroduction of the oxygenated solution). Mitochondrial viability and response were measured by staining with 3-[4.5 dimethylthiazol 2-yl]-2,5-diphenyltetrazolium bromide. The magnitudes of mitochondrial recovery after simulated ischemia and 28 possible risk factors for postoperative atrial fibrillation were entered into univariate and multivariate models.Results: There were no deaths in this group of patients. Nineteen patients (38%) had postoperative atrial fibrillation. Interestingly, no difference in baseline (before simulated ischemia) mitochondrial function was documented between patients who had postoperative atrial fibrillation and those who did not. An independent predictor for postoperative atrial fibrillation was the degree of mitochondrial dysfunction in response to simulated ischemia, as measured by the intensity of the staining.Conclusion: This study has identified for the first time an association between mitochondrial dysfunction in response to ischemia and postoperative atrial fibrillation. This finding improves our understanding of the pathophysiology of postoperative atrial fibrillation and may eventually lead us to identify candidates for selective preoperative or early postoperative prophylactic treatment.