Part 1 :
EDCA stands for “emergency department cardiac arrest” (Kim et al., 2023). In 2019, 232,000 cases of this condition occurred in the U.S. alone. That means the approximate incident rate in America was 0.2% that year (Kim et al., 2023).
There are many risk factors associated with cardiac arrest. Lifestle and medical condition-based risks include heavy alcohol use or binge-drinking, physical exertion, stress, emotional exertion, and previous or ongoing heart conditions such as coronary heart disease and congenital heart defects. These factors significantly increase the risk of cardiac arrest (National Heart, Lung, and Blood Institute, 2022). Additional risk factors are associated with age, gender, and race as well. According to the National Heart, Lung, and Blood Institute, people past the age of 30 are more likely to experience cardiac arrest. Furthermore, men are particularly vulnerable to cardiac arrest compared to women. However, black women and all women who have experienced or are experiencing menopause also face an increased risk of cardiac arrest.
As of 2022, the American Heart Association released a report on heart and stroke statistics.” According to the report, cardiac arrest remains a public health crisis. There are more than 356,000 out-of-hospital cardiac arrests (OHCA) annually in the U.S., nearly 90% of them fatal” (Sudden Cardiac Arrest Foundation, 2022).
Ischemia/reperfusion is a type of tissue damage that is caused by a lack of oxygen and blood supply to an area of the body. When the oxygen and blood supply return, the body attempts to repair itself, which leads to inflammation in the affected area (Wikipedia, 2024). This is a serious issue, as it prevents cells from creating ATP and other essential resources needed for cellular function and the body’s overall health.
“Intercellular Mitochondrial Transfer (IMT) is a dynamic cellular process central to intercellular communication, where mitochondria, the vital energy-producing organelles, are exchanged between adjacent or distant cells”(Regad, 2024). By transferring mitochondria, the adjacent cells are able to provide healthy mitochondria to cells that are in need of energy support (Kim et al., 2023). This is extremely beneficial to animal cells, as the mitochondria are extremely prone to damage if something goes wrong in a cell. It is also beneficial because the mitochondria play the important role of a component in maintaining homeostasis within cells (Kim et al., 2023). This process suggests that it is possible to artificially transplant a mitochondrion into an animal cell to combat mitochondrial diseases.
Part 2:
In the study by Hayashida et al. (2023), the researchers tested the effects of mitochondrial transplantation by utilizing rat subjects induced into cardiac arrest. Cardiac arrest leads to critical levels of oxygen deprivation in tissues, resulting in damage to cellular components and the failure of critical physiological functions. This study explored whether mitochondrial transplantation, specifically with cultured mitochondria, could improve outcomes following cardiac arrest. Based on the results presented in the article, transplanting cultured mitochondria into the rats was successful and provided the treated rats with more baseline function than the negative control specimens that received no mitochondrial intervention (Hayashida et al., 2023).
The study revealed significant findings in terms of survival rates and neurological outcomes among the experimental groups. As displayed in the results and accompanying figures, survival rates and levels of neurological function were consistently superior in rats treated with fresh mitochondria. Conversely, rats that received no mitochondrial treatment exhibited the worst survival rates and neurological performance. These findings highlight the efficacy of mitochondrial transplantation in improving critical outcomes following cardiac arrest.
In examining blood lactate levels, which serve as an indicator of metabolic dysfunction, the results showed an increase beyond baseline levels at 15 minutes following resuscitation. Among the experimental groups, the largest increase in blood lactate was observed in rats that received thawed mitochondria, but these levels were nearly identical to those observed in rats that received no treatment at all. This finding suggests that thawed mitochondria do not provide a significant benefit in terms of reducing lactate levels. On the other hand, rats treated with fresh mitochondria exhibited the lowest lactate levels. These findings point to the superiority of fresh mitochondrial transplantation in managing the metabolic consequences of cardiac arrest. Notably, at 120 minutes post-resuscitation, blood lactate levels in all groups returned to baseline values, indicating a natural recovery trend regardless of treatment. However, the earlier differences in lactate levels show the potential of fresh mitochondria to improve early metabolic recovery (Hayashida et al., 2023).
Another critical parameter examined in the study was tissue swelling, which serves as a marker of cellular damage and dysfunction. The results showed that rats treated with thawed mitochondria and those that received no treatment exhibited similar levels of swelling, which were the highest among all groups. By contrast, rats treated with fresh mitochondria displayed significantly lower levels of swelling. This observation supports the notion that fresh mitochondria are more effective at mitigating the cellular damage caused by cardiac arrest. The parallel findings between the thawed mitochondria group and the untreated group further suggest that the freezing and thawing process diminishes the efficacy of mitochondrial transplantation (Hayashida et al., 2023).
An additional finding of the study pertains to the persistence of transplanted mitochondria in the tissues of the rats. In the group treated with fresh mitochondria, the transplanted mitochondria remained detectable in the tissues for an extended period, with a gradual fade over the course of 24 hours. This persistence was especially evident when compared to the cells of the negative control group, which exhibited no transplanted mitochondria. The lingering presence of mitochondria in the treated rats suggests that these transplanted organelles integrate with host cells, potentially contributing to the observed improvements in survival and neurological outcomes (Hayashida et al., 2023).
Based on these findings, the researchers concluded that fresh mitochondrial transplantation provides the best results for survival, neurological function, and cellular recovery. The study highlights the superiority of fresh mitochondrial samples in terms of their ability to restore metabolic function, reduce swelling, and integrate into host tissues. These outcomes indicate that fresh mitochondria are a promising therapeutic option for improving outcomes following cardiac arrest. However, the study also demonstrated that frozen mitochondrial transplantation often produced results similar to those observed in the negative control group. This was particularly evident when examining parameters such as blood lactate levels and tissue swelling. These findings suggest that the freezing and thawing process may damage the mitochondria, rendering them less effective at improving outcomes. (Hayashida et al., 2023)
While fresh mitochondria consistently produce the best results, it should be acknowledged that thawed mitochondria are not entirely without potential. Although thawed mitochondria were less effective than fresh samples, their use still warrants further exploration, especially in scenarios where the availability of fresh mitochondria is limited. The logistical challenges associated with using fresh mitochondria in clinical settings, such as the need for immediate preparation and transplantation, highlight the importance of optimizing frozen mitochondrial protocols for future therapeutic use (Hayashida et al., 2023).
The findings of this study carry important implications for the development of novel treatments for cardiac arrest and other conditions associated with mitochondrial dysfunction. Cardiac arrest remains a major cause of mortality and neurological disability worldwide, and current treatment options are limited in their ability to address the underlying cellular damage caused by oxygen deprivation. By demonstrating the efficacy of mitochondrial transplantation, this study provides a potential pathway for improving outcomes in patients who suffer from cardiac arrest. However, additional research is needed to translate these findings into clinical practice. Future studies should focus on optimizing the preparation and delivery of mitochondria, particularly in terms of enhancing the viability and functionality of frozen samples. Furthermore, the mechanisms underlying the integration and function of transplanted mitochondria in host tissues require further investigation to maximize the therapeutic potential of this approach (Hayashida et al., 2023). This research represents an important step forward in the development of mitochondrial-based therapies. The study not only highlights the potential of mitochondrial transplantation as a therapeutic intervention but also the need for continued research to address the technical and logistical challenges associated with its implementation.
References:
Hayashida K., Takegawa R., Endo Y., Yin T., Choudhary R. C., Aoki T., Nishikimi M., Murao A., Nakamura E., Shoaib M., Kuschner C., Miyara S. J., Kim J., Shinozaki K., Wang P., & Becker L. B. (2023). Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest. BMC Medicine, 21(1), Page. 10.1186/s12916-023-02759-0
Regad T. (2021, July 9). Intercellular Mitochondrial Transfer. Publication_Title, https://healthquestionsmatters.com/intercellular-mitochondrial-transfer/
Hsu S., Sung C., Lu T., Wang C., Chou E. H., Ko C., Huang C., & Tsai C. (2024). The incidence, predictors, and causes of cardiac arrest in United States emergency departments. Resuscitation Plus, 17(Issue), 100514. 10.1016/j.resplu.2023.100514
https://www.sca-aware.org/about-sudden-cardiac-arrest/latest-statistics