Remote Ischemic Preconditioning Preserves Mitochondrial Function and Influences Myocardial MicroRNA Expression in Atrial Myocardium During Coronary Bypass Surgery

Abstract

RATIONALE: Remote ischemic preconditioning (RIPC) has been suggested to induce cardioprotection during cardiac surgery. Maintaining proper atrial function is imperative in preventing arrhythmia and thrombus formation. Mitochondria have been proposed as key targets in conveying RIPC mechanisms and effects. MicroRNA (miR) is emerging as an important regulator of mitochondrial function, arrhythmia, and protection from ischemia and reperfusion. OBJECTIVE: This study aimed to evaluate the effect of RIPC on mitochondrial respiration and miR expression in human atrial tissue. METHODS AND RESULTS: Sixty patients undergoing coronary artery bypass graft surgery were randomized to RIPC (n=30) or control (n=30). RIPC was performed preoperatively by inflating a blood pressure cuff on the upper arm to 200 mm Hg for 3×5 minutes, with 5 minutes reperfusion intervals. Biopsies were obtained from the right atrial appendage before and after aortic cross-clamping. Mitochondrial respiration was measured in situ and miR assessed by commercial miR array and quantitative reverse transcription polymerase chain reaction. Postoperative atrial fibrillation occurrence was monitored by biotelemetry. Maximal mitochondrial respiration was preserved throughout surgery after RIPC but significantly reduced (-28%; P<0.05) after aortic cross-clamping in control. Incidence of postoperative atrial fibrillation was lower after RIPC versus control (14% versus 50%; P<0.01). Myocardial expression of miR-133a and miR-133b increased after aortic cross-clamping in both RIPC and control, whereas miR-1 was upregulated in control only. MiR-338-3p expression was higher in RIPC versus control after aortic cross-clamping. CONCLUSIONS: RIPC preserves mitochondrial respiration and prevents upregulation of miR-1 in the right atrium during coronary artery bypass graft. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01308138.