Cardiac arrest is a medical issue that continues to plague the American population. The current rate of cardiac arrest incidence is estimated to be 200,000 to 250,000 people every year (Chugh et al., 2008). These findings are based on emergency department admittance across the United States (Hsu et al., 2024). There are multiple risk factors that can increase the risk of cardiac arrest, the greatest of which being heart problems, specifically coronary heart disease (USDHHS). Coronary heart disease and cardiac arrest have similar risk factors like increasing age, being a man, family history, and ethnicity. Specifically, black people have a higher risk than white people, while Hispanic and Asian people have a lower risk. Poor metabolic health can greatly increase your risk of cardiac arrest due to the increased rate of coronary heart disease and decreased heart performance.

An additional statistic includes about 350,000 hospital cardiac arrest events that occur every year. Of the outside hospital events, approximately 90 percent result in fatality. (Sudden Cardiac Arrest Foundation) That is a total of 600,000 cardiac events a year. The fatality rate does go down in the hospital, but the one-year survival rate is only about 20% (Hickman, 2023).

Ischemia is defined as a lack of blood flow to an organ or area of the body. This can be caused by atherosclerosis, low blood pressure, blood clots, or certain medical devices. In some instances, it can be as serious as near instant death due to lack of blood flow and therefore oxygen to the brain or heart. In other instances, it can result in tissue death, like gangrene to an affected body part. This is also a possibility if someone applies a tourniquet to an extremity because it would cause a lack of blood flow to the limb. This may also save their lives because it prevents an excess loss of blood depending on the wound (Cleveland Clinic).

Reperfusion, on the other hand, is the introduction of blood to a body part that has previously experienced an ischemic condition. Restoring blood flow to an area that has previously lacked blood flow and oxygen can result in serious problems depending on the time without blood flow. This condition can result in damage to blood vessels and result in cells abnormally diffusing to other tissues that results in damage, making it a delicate process (Project C, 2024).

Simply put, intercellular mitochondrial transfer is the transfer of mitochondria between different cells. This is generally done for the purpose of rejuvenating and aiding damaged cells. This can be done physiologically or pathologically as well as during more focused treatments. These mechanisms provide inspiration for mitochondrial transplant, which uses medical innovation to treat mitochondrial disorders by transporting mitochondria as well as the contents of mitochondria like RNA and DNA. (Liu D. et al, 2021).

The process of transplant and transfer can be executed by multiple mechanisms, including tunneling nanotubes, extracellular junctions, and gap junction channels. (Liu Z. et al, 2022). There is an effort to develop this field as it has shown promise with mtDNA mutations and cancer treatments. These methods have specific applications related to neurons and neurology. Additionally, there exist links to ischemia related issues that the transplant and transfer due to the reactive oxygen species localizing in the mitochondria resulting in degraded mitochondrial performance. Research is on going in this field. One promising study discusses exogenous mitochondrial transplant in rats.

The study was used to assess the use of exogenous mitochondrial transplant of neural cells following cardiac arrest. The hypothesis from the experiment states that exogenous mitochondrial transport will increase the length of life after resuscitation from a cardiac event (Hayashida et al., 2023). The study varied a couple of factors in the experiment, including the use of a vehicle standard, frozen then thawed non-functional mitochondria, and fresh mitochondria in both in vitro and in vivo experiments.

In these experiments, it is determined that mitochondria are able to transfer into neural cells, and they are functional if fresh mitochondria are inserted. The mitochondria from the exogenous implant were stained red while the endogenous mitochondria were stained blue. After being inserted in vitro into the neural cell culture media, it was depicted that both sets of mitochondria remained. Since the nonfunctional and vehicle groups were two different versions of a negative control group, the team expects the two groups to remain the same while the fresh group is expected to have better results if the mitochondria were functional.

Overall survival of the rats following resuscitation from a cardiac arrest event was 55% for both negative control groups and 91% for the fresh group. This demonstrates that the rats with the exogenous mitochondria had a much higher rate of survival at the 72-hour point than those that did not. The frozen then thawed group of rats did show a slight increase in mitochondrial function compared to the vehicle standard, but was three times less efficient than the fresh mitochondria group producing around 320 nano-mol per liter per 10 microliters. Another metric assessed by the team noted that neurological function was slightly raised by the frozen then thawed group and greatly bettered by the fresh group. Even in the fresh group, the neurological function scores achieved the rate were 200 less than the average rat before a cardiac event but 150 greater than the vehicle standard. The scale of zero being a dead rat and 500 being a normal rat. In the rats who received the fresh mitochondria, the body weight of the rats had the closest return to normal 72-hours following the event, while both negative control groups had a similarly lower number.

Arterial lactate was measured on all the rats, and it was discovered that 15 minutes after the resuscitation, the rats who received the fresh mitochondria had about half the level of lactate in their blood compared to both negative control groups. After 120 minutes, all three groups returned to approximately the same original baseline. Another measured factor was the occurrence of pulmonary edema measured by water content in the lungs, which had a ratio over 1.5 lower than both negative control groups. One relatively stable factor amongst all groups was heart rate, arterial pressure and left ventricle ejection pressure, which was consistent amongst all three groups studied when monitored for two hours following resuscitation. Glucose normally increases immediately after in patients who endure cardiac arrest. For rats that received the fresh mitochondria, levels only rose 1.25 times the baseline compared to 1.6 x the baseline in both negative control groups in the first fifteen minutes. After two hours, all groups returned to approximately baseline. Other measured metrics include pH and pCO2. After 15 minutes, pH lowered by half of what both negative control groups did before all three groups stabilized near baseline after 120 minutes. PCO2 had similar benefits, raising only slightly compared to both negative control groups after 15 minutes. All pCO2 returned to baseline following two hours after the resuscitation.

Laser speckled contrast imaging showed that the fresh mitochondria group had nearly identical blood flow to the brain before and after the induced cardiac arrest event. This differs from the slightly weakened blood flow linked to the frozen then thawed group and the greatly weakened vehicle group. Fresh mitochondria was documented to remain in the rats’ hearts, lungs, and spleen both one hour and twenty-four hours after the resuscitation. When analyzed past 24 hours, the amount of mitochondria does not persist in the tissues.

Overall, the injection of rats in vivo with fresh mitochondria seemed to have numerous positive effects for rats that experienced resuscitation ten minutes after an induced cardiac arrest event. The rats had an increased survival rate, increased ATP production from increased mitochondrial function, and increased neurological function after the induced event. These all demonstrate a greater life efficacy compared to the control group. Additionally, the rats who received intravenous fresh mitochondria had a closer return to original body weight and a lower instance of pulmonary edema. The rats also had smaller spikes in pCO2, pH, glucose and lactate than both negative control groups in the 15 minutes following the induced event. While they saw no changes in the heart rate, mean arterial pressure, or left ventricle ejection pressure, they did notice increased blood flow to the brain compared to both negative control groups.

When comparing the frozen then thawed mitochondria to the fresh mitochondria, the frozen then thawed mitochondria are not one hundred percent non-functional. The team documented some increased ATP production, increased blood flow to the brain, and increased neurological function, implying there is some functionality to the frozen then thawed exogenous mitochondria. However, these results pale in comparison to the exogenous fresh mitochondria which as improvement in nearly every monitored metric as well as life expectancy. Therefore, one could use mitochondria that were originally frozen, but it would not yield all the benefits that fresh mitochondria do. So, the use of fresh mitochondria is preferred and the only way out of these three groups will increase the survival chance of the rats after an induced cardiac arrest event.

This paper demonstrated multiple facets of mitochondrial function discussed in class. We have seen that for the electron transport chain in the mitochondria to produce ATP, oxygen is required, and we can see increased ATP production from the fresh mitochondria injections. There is increased blood flow to the body and increased production of ATP consequently. The increase in glucose consumed and lactate present makes sense due to the strain on the body after resuscitation in both negative control groups. That is, lactate dehydrogenase produces lactate as opposed to continuing to the citric acid cycle when breaking down glucose due to the lack of effective oxygen consumption. This is less of a problem in the rats injected with the fresh mitochondria. In conclusion, there were more functioning mitochondria in the rats injected intravenously with both frozen than thawed and fresh mitochondria, demonstrated by the amount of ATP produced, respectively. This is demonstrated by measured ATP levels, glucose levels, lactate levels, survival rate, and more in the research paper.