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Remote ischemic preconditioning preserves mitochondrial function and influences myocardial microRNA expression in
Katrine Hordnes Slagsvold1, Oivind Rognmo, Morten Høydal
1From the K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and technology, Trondheim, Norway (K.H.S., O.R., M.H., U.W., A.W.); and Department of Cardiothoracic Surgery, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway (K.H.S., A.W.).
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.
Insights
Remote ischemic preconditioning (RIPC) preserves mitochondrial function and reduces atrial fibrillation after heart surgery. This cardioprotective effect involves maintaining mitochondrial respiration and altering microRNA expression.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Molecular Medicine
Background:
- Remote ischemic preconditioning (RIPC) shows promise for cardioprotection during cardiac surgery.
- Atrial function is critical for preventing arrhythmia and thrombus formation.
- Mitochondria and microRNAs (miRs) are implicated in RIPC mechanisms and atrial health.
Purpose of the Study:
- To investigate the impact of RIPC on mitochondrial respiration in human atrial tissue.
- To assess changes in microRNA expression following RIPC during cardiac surgery.
- To correlate RIPC effects with the incidence of postoperative atrial fibrillation.
Main Methods:
- Randomized controlled trial with 60 patients undergoing coronary artery bypass graft surgery.
- RIPC applied preoperatively via arm cuff inflation; atrial biopsies taken before and after aortic cross-clamping.
- In situ mitochondrial respiration assays, miR expression analysis (array and qRT-PCR), and postoperative atrial fibrillation monitoring.
Main Results:
- RIPC maintained maximal mitochondrial respiration post-surgery, unlike controls (-28% reduction).
- Postoperative atrial fibrillation incidence was significantly lower in the RIPC group (14% vs. 50%).
- RIPC modulated miR expression, notably increasing miR-338-3p and preventing miR-1 upregulation.
Conclusions:
- RIPC effectively preserves mitochondrial respiration in the right atrium during coronary artery bypass graft surgery.
- RIPC demonstrates a protective effect against postoperative atrial fibrillation.
- RIPC influences specific microRNA profiles in the atrium, contributing to cardioprotection.
