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.

Abstract

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. 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. 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. 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.