Myocardial Physiology in Individuals Undergoing Heart Surgery
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Mitochondria are essential organelles in all eukaryote cells. They produce the vast majority of all the energy the heart needs to continuously pump oxygenated blood throughout the body. The myocardium is entirely dependent on well-functioning mitochondria. There are indications that altered mitochondrial function is implicated in mediation of cardioprotection from remote ischemic preconditioning (RIPC), as well as in atrial fibrillation (AF). RIPC involves exposing a part of the body to repeated brief periods of ischemia to evoke a protective effect in another organ such as the heart. Although ischemic preconditioning has been a focus of research for nearly three decades, there are still several aspects that remain unexplained. AF is the most prevalent cardiac arrhythmia of clinical relevance, and a thorough understanding of the underlying pathophysiology is important to improve therapeutic and preventive strategies. MicroRNA (miRNA) are a group of small molecules that regulate protein expression at a post-transcriptional level through inhibition and degradation of mRNA. There is emerging evidence that miRNA may have a role in cardiac ischemiareperfusion injury, as well as in AF. However, due to their relatively recent discovery, there are still many unanswered questions. The main aims of this thesis are to investigate human myocardial physiology during cardiac surgery in association with RIPC and AF. Atrial and ventricular biopsies were obtained upon consent from patients undergoing open heart surgery at Clinic of cardiothoracic surgery, St. Olav’s hospital. Mitochondrial function was assessed in situ after tissue permeabilization by saponin. MiRNA expression was investigated through array and PCR technology. We found that RIPC preserves myocardial mitochondrial respiration in heart surgery, and affects microRNA expression. Mitochondrial respiratory capacity was elevated in patients with AF as compared to patients with normal sinus rhythm. The expression of microRNA differed between the right vs. left atrium of patients with sinus rhythm and AF, whereas mitochondrial function was similar in the right and left atrium of both groups. The main conclusion of our study is that there are indications that mitochondrial function and microRNA are involved in AF pathophysiology, as well as in RIPC, and should be investigated further for future clinical application.
Består avPaper 1: Slagsvold, Katrine Hordnes; Rognmo, Øivind; Høydal, Morten Andre; Wisløff, Ulrik; Wahba, Alexander. Remote ischemic preconditioning preserves mitochondrial function and influences myocardial MicroRNA expression in atrial myocardium during coronary bypass surgery. Circulation Research 2014 ;Volum 114.(5) s. 851-859, is not included due to copyright. Available at http://dx.doi.org/ 10.1161/CIRCRESAHA.114.302751
Paper 2: Slagsvold, Katrine Hordnes; Moreira, Jose Bianco Nascimento; Rognmo, Øivind; Høydal, Morten; Bye, Anja; Wisløff, Ulrik; Wahba, Alexander. Remote ischemic preconditioning preserves mitochondrial function and activates pro-survival protein kinase Akt in the left ventricle during cardiac surgery: A randomized trial. International Journal of Cardiology 2014 ;Volum 177.(2) s. 409-417 http://dx.doi.org/ 10.1016/j.ijcard.2014.09.206
Paper 3: Slagsvold, Katrine Hordnes; Johnsen, Anne Berit; Rognmo, Øivind; Høydal, Morten; Wisløff, Ulrik; Wahba, Alexander. Mitochondrial respiration and microRNA expression in right and left atrium of patients with atrial fibrillation. Physiological Genomics 2014 ;Volum 46.(14) s. 505-511 is not included due to copyright. available at http://dx.doi.org/ 10.1152/physiolgenomics.00042.2014
Paper 4: Slagsvold, Katrine Hordnes; Johnsen, Anne Berit; Rognmo, Øivind; Høydal, Morten; Wisløff, Ulrik; Wahba, Alexander. Comparison of left versus right atrial myocardium in patients with sinus rhythm or atrial fibrillation - an assessment of mitochondrial function and microRNA expression.. Physiological Reports 2014 ;Volum 2.(e12124) http://dx.doi.org/10.14814/phy2.12124 Copyright © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
SerieDoctoral thesis at NTNU;