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The Role of Mitochondria in Cyanotic and Acyanotic Congenital Heart Disease

Objectives: Congenital heart disease (CHD) is one of the most specialized field of heart surgery and compelling approaches such as mitochondrial transplantation is creating promising options. Therapeutic options are available, but lack of data on mitochondrial function in this disease group. Hence, we hypothesized that there is a differential level mitochondrial dysfunction in cyanotic vs acyanotic CHD groups and aimed to indicate any potential pediatric patient group that is suitable for this innovating therapeutic approach. Hence, in this study, mitochondrial morphology and function, myocardial fibrosis, and myocyte atypia were evaluated in myocardial tissue of pediatric patients with cyanotic and acyanotic CHD. Additionally, cardiac enzymes have been reviewed as a potential indicator for postoperative follow-up. 
 
Methods: 5 acyanotic CHD and 5 cyanotic CHD patients were included according to clinical parameters of patients. During the open heart surgery, myocardial biopsies (2–3 mm³) were obtained from right atrium. Mitochondrial morphology was evaluated by immunofluorescence staining using anti-Tom20 antibody, electron transport chain complexes of myocardium were examined by histological cytochrome c oxidase/succinate dehydrogenase (COX/SDH) histochemical staining and ATP production was measured. Hematoxylin and eosin, and Masson ’ s trichrome staining were used to determine histopathological changes. In both preoperative and postoperative period, cardiac enzymes of each patient were monitored. Myocyte atypia, and fibrosis were classified on a scale of 1 to 4. All data were analyzed to determine any correlation between all parameters. 
 
Results: In the research study, unlike patients with acyanotic CHD, alterations in mitochondrial network and reduction in ATP production were detected in all pediatric patients with cyanotic CHD. These findings may be assumed as an evidence for the relationship between mitochondrial dysfunction and cyanotic CHD. As well as, statistically significant correlation was determined between mitochondrial dysfunction and cardiac enzyme levels. Conclusion: Due to the fact that mitochondrial in myocardium of pediatric patient group with cyanotic CHD were determined, mitochondrial transplantation may be considered as a futuristic therapeutic approach to increase the surgical success in patients with cyanotic CHD. 
 
Funding Statement: This work was supported by Hacettepe University Scientific Research Projects Coordination Unit, Project Number: THD-2018-16687 
 
Declaration of Interests: There is no conflict of interest. 
 
Ethics Approval Statement: This study protocol was approved by Hacettepe University Faculty of Medicine Ethical Review Board (GO 17/651). Additionally, on behalf of all named authors, I, the Corresponding Author, declare that all experiments were performed in accordance with guidelines, and regulations of Declaration of Helsinki.