Myocardial Physiology in Individuals Undergoing Heart Surgery
Doctoral thesis
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http://hdl.handle.net/11250/278473Utgivelsesdato
2014Metadata
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Sammendrag
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 av
Paper 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.114.302751Paper 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.
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NTNUSerie
Doctoral thesis at NTNU;;2014:356