- First opponent: Professor Godfrey Smith, Institute of Cardiovascular and Medical science, University of Glasgow, Scotland
- Second opponent: Professor Ellen Aasum, Cardiovascular Research Group, Department of Medical Biology, Faculty of Health Science– The Arctic University of Norway, Tromsø
- Third member and chair of the evaluation committee: Professor Torbjørn Omland, Institute of Clinical Medicine, Akershus University Hospital and University of Oslo
Chair of the defence: Professor Em. Ingebjørg Seljeflot, University of Oslo
Principal Supervisor: Professor Mathis Korseberg Stokke, University of Oslo
Regular physical activity protect against cardiovascular disease. However, exercise can provoke fatal heart rhythm disturbances in some conditions. Patients with heart failure have increased risk of heart rhythm disturbances. On a cellular level, heart failure share some alterations with the rare disease catecholaminergic polymorphic ventricular tachycardia (CPVT). Both diseases have altered ryanodine receptor (RyR) function. Calcium release by RyR in the cardiomyocytes controls electric activity and contraction of the heart. Release of calcium in the diastole due to RyR dysfunction increases the propensity for arrhythmias, cardiac arrest and sudden cardiac death. Previous research has indicated that exercise can modify RyR function.
In this doctoral thesis, Tore Kristian Danielsen and coworkers have investigated the mechanisms behind disrupted calcium handling in CPVT and heart failure and the effect of exercise on this mechanism for arrhythmias.
The first paper confirmed that stress-stimulation of the heart is the most important stimuli for arrhythmia development in CPVT, but also that increased heart rate might contribute independently through potentiated release of calcium.
In paper two and three, we investigate the anti-arrhythmic effect of exercise in CPVT and heart failure, respectively. We found that exercise attenuated abnormal calcium release in cardiomyocytes, which might decrease the propensity for arrhythmias.