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Remote ischaemic preconditioning increases serum extracellular vesicle concentrations with altered micro‐RNA signature in CABG patients
Author(s) -
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
Publication year - 2019
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.13296
Subject(s) - medicine , cardioprotection , ischemic preconditioning , isoflurane , ischemia , anesthesia , sufentanil , venous blood , cardiology , cardiopulmonary bypass
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 < 0.05) isolated from EVs including the cardioprotective miR‐21 had increased. RIPC also decreased postoperative Troponin I concentrations (AUC RIPC: 336 ng/mL × 72 hours ± 306 vs Sham: 713 ± 1013; P = 0.041). Conclusions Remote ischaemic preconditioning increases serum EV concentrations, most likely by early EV release from the patients’ left (RIPC) arm, alters their miRNA signature, and is associated with myocardial protection. Thus, an increased EV concentration with an altered miR‐signature may mediate the RIPC effect.