In 2024, cardiac arrest remain the leading cause of death in the US and taking around 450,000 lives each year as most attacks occur outside a clinical setting with only a 10% chance of survival (Latest Statistics). In 2010, research concluded that about three percent of adults over 20 years old in the US will experience a heart attack in his or her lifetime. Based on the 2022 Heart and Stroke Statistics research done by the American Heart Association, 90% of out-of-hospital cardiac arrests are fatal, and 74% of in-hospital occurrences are fatal. Risks factors associated with cardiac arrest may include lifestyle habits such as heavy alcohol consumption, recreational drugs, stress-heavy work, low exercise, or poor diet. Additionally, the risks of a heart attack may increase based on age, family history, or other prevalent heart problems such as arrhythmias (irregular heart beat). For the most part, cardiac arrest can be heavily dependent on lifestyle, which is why doctors may always recommend diet changes, exercise, or even recommend meditation as a form of stress relief to lower risks.
Ischemia is a health condition where there is a lack of blood supply for a part of the body which can lead to tissue damage or organ dysfunction. In relation to the cardiovascular system, this means that the heart is not getting enough blood and therefore not enough oxygen to continue functioning properly. To counteract this, the repercussion is the restoration of blood flow to an ischemic tissue or organ such as the heart. Although this may sound like a good thing, reintroducing blood flow to ischemic tissue or organs may cause further damage. This is known as ischemia-reperfusion injury and can be summarised as cellular damage after reperfusion occurs. This injury includes symptoms such as pain with no visual physical damage, decreased pulsation, and decreased feeling in the affected limb. When it comes to the cardiovascular system, ischemia-reperfusion injury directly effects cardiomyocytes (muscle cells found in the heart) due to the increased production of oxygen free radicals as this damages them, leading to apoptosis and necrosis of the cardiomyocytes. Circling back to cardiac arrests, because of the risks of reperfusion injury to the heart after a heart attack, timing is everything; healthcare professionals have found that as long as an angioplasty (widening of an obstructed vein or artery) is done and reperfusion occurs within two hours of the attack, recovery is at a lesser risk (Brodie).
Intercellular mitochondrial is a type of intercellular communication in which the mitochondria move from cell to cell. This process is very important to cellular health as it can regulate development, reprogram cells, and alleviate injury. When it comes to mitochondrial transplants, this suggests possible therapeutic approaches for diseases caused by mitochondrial dysfunction such as metabolic disorders and cancer. Based on research published by the NLM in 2023, scientists found that the mitochondria were more active than initially interpreted when it came to travelling across cells (Chile F.). For humans, this means that there is potential to restore dysfunctional mitochondria by transferring mitochondria from donor cells to cells in need. In relation to the thousands of Americans who suffer cardiac arrests each year and have damaged cardiomyocytes; mitochondrial transplants have the potential to allow for the exchange of functional mitochondria to other cells in the heart, which allows for the cells to receive more support. This is very significant because when heart cells are damaged after a cardiac arrest, the injured mitochondria may transfer to other cells to signal for help from healthier mitochondria; in turn, this may cause more damage if healthier mitochondria are not in abundance.
Based on Fig.1 in the research article, mitochondria can successfully be transplanted into neural cells. This is evident as the figure shows the complete overlap of endogenous mitochondria and exogenous mitochondria; building a yellow rings in the fully merged image in the A row. In the B row of Fig.1, the claim is supported as the endogenous and exogenous mitochondria overlap, and create yellow dots in the fully merged image.
In Fig.2, it is suggested that the transplanted mitochondria are functional to an extent. The B graph was an insight on the mitochondrial membrane charge, and reveal if the transplanted mitochondria are functional, or not. This includes the tests of fresh mitochondria that were transferred as well as frozen-thawed mitochondria to fully evaluate and compare the amount of healthy mitochondria and unhealthy mitochondria. Based on this graph, the JC-1 dye used for testing glowed red particularly for fresh mitochondria which suggests the presence of healthy, functioning mitochondria. However, frozen-thawed mitochondria showed little to no healthy, functioning mitochondria as the JC-1 dye turned green and indicated unhealthy mitochondria. Based on these figures, it is scientifically proven that mitochondria can successfully be transplanted into neural cells, and function properly; however, there are limitations to function. These figures revealed the poor outcome of using frozen-thawed mitochondria cells for transplantation as they will not function properly. Therefore, this data suggests scientist must use fresh mitochondria when performing transplantations to have a more successful outcome of healthy, transplanted mitochondria. It is important to note that the study continues to compare the outcomes of using frozen-thawed mitochondria versus fresh mitochondria as this gives scientists more data for comparison.
One of the main purposes of this study is to discover if mitochondrial transplants increase survival following cardiac arrest which is notated in Fig. 3. In Fig.3 A, the use of fresh mitochondria in transplant showed a greater survival rate of the rats between 12-72 hours post cardiac arrest compared to rats with frozen-thawed transplanted mitochondria. This could suggest that transplanted mitochondria has the potential to increase survival rate post cardiac arrest.
The scientist next test the neurological state of the rats, separated by whether they received fresh mitochondria or frozen-thawed mitochondria. In Fig. 3 B, scientists released the data of the test they conducted called the Neurological Function Test for the rats 72 hours post cardiac arrest. The data was surprisingly close between the rats who received frozen-thawed mitochondrial transplants and fresh mitochondrial transplants as the difference was 0.0469 between score with the fresh mitochondria rats in the lead. This could indicate the improvement of neurological function following a cardiac arrest with a mitochondrial transplant.
In this study, it was important for scientists to discover of the impact on overall health post cardiac arrest with mitochondrial implantation. In Fig. 3 C, scientists measured the body weights of the rats as this is a large indicator of health; less weight could mean potential illness, and more weight could mean the rat is healthier. The figure almost immediately signifies the weight loss of all rats between 12-48 hours post cardiac arrest; however, the rats with fresh mitochondria showed small weight increase around hour 72 post cardiac arrest. When compared to frozen-thawed mitochondria, these rats were continuing to slope downward, and losing weight with no sign of improvement around hour 72 of post cardiac arrest. Next, data was collected regarding the lactate blood levels, lung edema, and heart function of the rats two hours post cardiac arrest. Fig. 4 A indicated that the lactate blood levels of the rats returned to baseline quicker when they received a fresh mitochondria transplant versus frozen-thawed mitochondria and the vehicle. When it came to lung edema, in Fig. 4 B, the fresh mitochondria, again, had better recovery two hour post cardiac arrest when compared to frozen-thawed mitochondria and the vehicle. Additionally, it should be noted that there was almost no improvement for rats with frozen-thawed mitochondria and showed less improvement than the vehicle. Scientists then looked at heart function which resulted in almost tie between frozen and fresh mitochondria; however, the frozen mitochondria showed slightly better improvement in heart function two hours post cardiac arrest. Next, scientists tested the glucose levels of the rats as after cardiac arrest, glucose levels will normally rise. In Fig. 5 C, the goal is for the glucose levels of the rats to return to baseline post cardiac arrest, and the figure indicates the rats with fresh mitochondria were returning to the glucose baseline at much greater length than the frozen mitochondria and vehicle. Lastly, scientists looked at the blood flow to the brain post cardiac arrest for rats with frozen-thawed and fresh mitochondrial transplants. In Fig. 7 A, this is interpreted as the fresh mitochondria showed improvement of blood flow to brain post cardiac arrest when compared to the baseline; additionally, these mitochondria had the most improvement overall when compared to frozen-thawed and vehicle. The frozen-thawed and vehicle mitochondria showed less blood flow to the brain on hour two post cardiac arrest compared to hour one. Overall, the data points towards fresh mitochondria for implant transplants to lead to better health improvements post cardiac arrest.
In this study, it was also important for scientists to determine if the transplanted mitochondria persisted in the tissues. Based on Fig. 8, the figure indicates that not only did the mitochondria persist in the tissue, but the numbers of mitochondria slightly grew.
References
Hayashida, K., Takegawa, R. Endo, Y., Yin., Yin, T., Choudhary, R. C., Aoki, T., … & Becker, L. B. (2023). Exogenous mitochondrial transplantation improves survival and neurological outcomes after rescuscitatin from cardiac arrest. BMC medicine, 21 (1), 56.
Chile F., Clemente-Suárez V., Martín-Rodríguez A., Spain F., Tornero-Aguilera J., & Yáñez-Sepúlveda R. (Publication_Date). Mitochondrial Transfer as a Novel Therapeutic Approach in Disease Diagnosis and Treatment. PubMed Central (PMC), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218908/
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(2022, May 19). Causes and Risk Factors. NHLBI, NIH, https://www.nhlbi.nih.gov/health/cardiac-arrest/causes
TA; B. Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction. PubMed, https://pubmed.ncbi.nlm.nih.gov/9809941/