Remote ischaemic preconditioning increases serum extracellular vesicle concentrations with altered micro‐RNA signature in CABG patients

• Published in: Acta anaesthesiologica Scandinavica 2019-04, Vol.63 (4), p.483-492
• Main Authors: Frey, Ulrich H., Klaassen, Marina, Ochsenfarth, Crista, Murke, Florian, Thielmann, Matthias, Kottenberg, Eva, Kleinbongard, Petra, Klenke, Stefanie, Engler, Andrea, Heusch, Gerd, Giebel, Bernd, Peters, Jürgen
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anesthesia; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood pressure; Calcium-binding protein; Cell signaling; Coronary artery; Coronary Artery Bypass; Double-Blind Method; Extracellular Vesicles; Female; Heart Injuries - blood; Heart surgery; Humans; Ischemia; Ischemic Preconditioning, Myocardial - methods; Isoflurane; Male; Measurement methods; MicroRNAs - blood; Middle Aged; miRNA; Patients; Postoperative Complications - blood; Preconditioning; Reperfusion; Ribonucleic acid; RNA; Sufentanil; Surgery; Troponin; Troponin I; Troponin I - blood
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/aas.13296

Background Remote ischaemic preconditioning (RIPC) can attenuate myocardial ischaemia/reperfusion injury but its underlying mechanisms remain largely unknown. Recently, extracellular vesicles (EVs) containing microRNAs (miRNAs) were shown to mediate distant intercellular communication that may be involved in cardioprotection. We tested the hypothesis that RIPC in anaesthetized patients undergoing coronary artery bypass (CABG) surgery results in the release of EVs from the ischaemic/reperfused arm into the blood stream harbouring cardioprotective miRNAs. Methods In 58 patients randomised to RIPC (three 5/5 minutes episodes of left arm ischaemia/reperfusion by suprasystolic blood pressure cuff inflations/deflations) or Sham, a subprotocol comprising of parallel right radial artery and regional (left subclavian) venous blood sampling before (awake) and 5 and 60 minutes after RIPC/Sham during isoflurane/sufentanil anaesthesia could be completed. EVs were extracted by polymer‐based precipitation methods, their concentrations measured, and their miRNA signature analysed. Results Five minutes after RIPC, regional venous EV concentrations downstream from the cuff increased and arterial concentrations increased after 60 minutes (fold change [fc]: RIPC: 1.33 ± 0.5, Sham: 0.91 ± 0.31; P = 0.003 for interaction). Already 5 minutes after RIPC, expression of 26 miRNAs (threshold fc: 3.0, P