Cell-Permeable Succinate Improves Platelet Respiration in Patients Undergoing Cardiopulmonary Bypass: A Pilot Study
1 Institute of Cardiovascular Diseases, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania; (A.P.M.); (L.P.)
2 Center for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania; (A.M.B.); (D.G.B.); (A.L.)
3 Department III—Functional Sciences—Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania
4 Department VII—Internal Medicine—Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania;
5 Department VI—Cardiology—Cardiovascular Surgery, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania;
6 Mitochondrial Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden
7 Abliva AB, Medicon Village, 223 81 Lund, Sweden
8 Department IX—Surgery—Surgical Semiology I, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania;
9 Center for Hepato-Biliary and Pancreatic Surgery, “Victor Babeș” University of Medicine and Pharmacy, Timișoara, 2 Eftimie Murgu Sq., 300041 Timișoara, Romania
* Correspondence: (D.M.M.); (E.E.)
† These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 24 Jul 2022 / Revised: 2 Aug 2022 / Accepted: 4 Aug 2022 / Published: 16 Aug 2022
Abstract
Open-heart surgery with cardiopulmonary bypass (CPB) remains the standard approach for complex cardiac pathologies, such as advanced coronary heart disease and severe valvular defects. Platelet dysfunction has been widely reported, with both structural and functional changes being elicited by the CPB circuit. Succinate is a mitochondrial substrate that is metabolized through complex II (CII) but is impermeable to cellular membranes when given exogenously. Cell-permeable succinates are novel prodrugs developed to support mitochondrial electron transport (ET) and prevent energy depletion in various pathologies. The aim of the present pilot study was to investigate the role of NV118 (diacetoxymethyl succinate), a cell-permeable succinate, on platelet respiration in a pilot group of patients undergoing CPB. Blood samples (20 mL) were collected from participants before (prior to heparin administration) and after CPB (within 10 min after protamine sulphate administration). Platelets were isolated through a two-step centrifugation protocol. Mitochondrial respiration was analyzed by means of high-resolution respirometry in the presence of NV118 or its solvent (DMSO). The main respiratory parameters recorded were as follows: ROUTINE respiration, LEAK respiration, and maximal uncoupled respiration for both CI and CII (ET capacity) and for CII solely after CI inhibition (ET CII capacity). Here, we report that NV118 elicited a global increase in platelet respiration both pre- and post-CPB. In conclusion, NV118, a cell-permeable succinate, improved platelet bioenergetics in the setting of cardiopulmonary bypass. Whether the compound can support platelet function and/or provide organ protection at the mitochondrial level during CPB are clearly worthy and important areas for future investigation.
Keywords: cardiopulmonary bypass; platelets; mitochondrial respiration; high-resolution respirometry; cell-permeable succinate
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CITE
Merce, A.P.; Bînă, A.M.; Avram, V.F.; Buriman, D.G.; Lascu, A.; Feier, H.B.; Petrescu, L.; Muntean, D.M.; Elmér, E.; Crețu, O.M. Cell-Permeable Succinate Improves Platelet Respiration in Patients Undergoing Cardiopulmonary Bypass: A Pilot Study. Timisoara_Med 2022, 2022, 2.
Merce AP, Bînă AM, Avram VF, Buriman DG, Lascu A, Feier HB, Petrescu L, Muntean DM, Elmér E, Crețu OM. Cell-Permeable Succinate Improves Platelet Respiration in Patients Undergoing Cardiopulmonary Bypass: A Pilot Study. Timisoara Medical Journal. 2022; 2022(2):2.
Merce, Adrian P.; Bînă, Anca M.; Avram, Vlad F.; Buriman, Darius G.; Lascu, Ana; Feier, Horea B.; Petrescu, Lucian; Muntean, Danina M.; Elmér, Eskil; Crețu, Octavian M. 2022. "Cell-Permeable Succinate Improves Platelet Respiration in Patients Undergoing Cardiopulmonary Bypass: A Pilot Study." Timisoara_Med 2022, no. 2: 2.
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