Targeting Mitochondrial Injury: The Future of Post-Cardiac Arrest Resuscitation Care - TMED 801

TMED Blog

| 8 January 2025

By: Karam Alosta, TMED MSc '26 (Candidate) and TMED 801 Student

On November 7, 2024, the Department of Medicine hosted a thought-provoking Medical Grand Rounds presentation by Dr. Willard W. Sharp, an emergency physician-scientist who treats critical care patients at UChicago. Dr. Sharp’s talk, titled "Targeting Mitochondrial Injury: The Future of Post-Cardiac Arrest Resuscitation Care," delved into innovative approaches for post-cardiac arrest treatment.

Dr. Sharp highlighted the remarkable role of mitochondrial injury in post-cardiac arrest recovery. Mitochondria are the cell’s powerhouses, responsible for generating energy. When cardiac arrest occurs, a shortage of oxygen (ischemia) causes instant mitochondrial damage, and when blood flow is restored (reperfusion), furthermore mitochondrial injury could occur. This double damage is a prime cause of cell death, organ dysfunction, and poor recovery in cardiac arrest survivors.

Emergency medicine has made significant strides since the 1960s. Innovations such as the introduction of epinephrine, defibrillation, CPR, and mild hypothermia in 1999 have substantially improved patient survival after cardiac arrest. However, challenges remain, specifically in addressing multi-organ failure, brain injury, and the realization of the oxygen management mechanisms after resuscitation.

Dr. Sharp emphasized Drp1 (Dynamin-related protein 1), a chief regulator of mitochondrial fission, as a potential target for therapy. Inhibiting Drp1 could decrease mitochondrial fragmentation and prohibit further damage, enhancing recovery after cardiac arrest. Moreover, enhancing mitochondrial respiration and protecting key complexes (such as Complex I) from oxidative damage can stabilize cellular energy production and decrease harmful Reactive Oxygen Species (ROS).

Current post-cardiac arrest protocols typically include CPR, epinephrine administration, and ventilation support, followed by post-resuscitation interventions such as Targeted Temperature Management (TTM) and drugs targeting mitochondrial fission and fusion, like Drp1. These interventions are intended to protect mitochondria from the harmful effects of ischemia and reperfusion, eventually, improving survival and neurological outcomes.

According to Dr. Sharp, oxygen plays a crucial role during the recovery phase. Fairly controlled oxygen delivery assists in stabilizing mitochondrial function and supports neurological recovery. Striking the correct balance of oxygen can decrease oxidative stress while enhancing mitochondrial health and promoting overall survival rates.

The pathophysiology of post-cardiac arrest includes ischemia, reperfusion injury, inflammation, mitochondrial dysfunction, and multi-organ failure. Finally, Dr. Sharp shared his vision for the future of post-cardiac arrest care includes a multi-faceted approach to managing post-cardiac arrest patients, where advancements in mitochondrial biology and precision medicine could dramatically improve outcomes for cardiac arrest survivors. He emphasized that targeting mitochondrial dysfunction, alongside improving oxygen utilization, might transform the prognosis for these patients, even in cases with delayed resuscitation will improve both survival rates and neurological recovery.

After the presentation, Dr. Sharp engaged with the TMED students in a wide-ranging discussion. He began by sharing his career journey, explaining how he chose to pursue a clinical career after completing his PhD. The conversation then shifted to how his research can be applied in translational medicine to enhance patient care. He assured that the understanding of mitochondrial dysfunction in post-cardiac arrest is vital for improving clinical outcomes in patients who experience cardiac arrest, myocardial infarction, or traumatic injury. Dr. Sharp concluded the discussion by highlighting the importance of ongoing research into the role of oxygen in post-cardiac arrest recovery. He expressed optimism that in the next 5-10 years, breakthroughs in mitochondrial biology, precision medicine, and post-cardiac arrest care will significantly improve survival rates and the quality of life for patients.

References

Piao L, Fang YH, et al. Dynamin-related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury. FASEB J. 2024 Jan;38(1):e23379. doi: 10.1096/fj.202301040RR. PMID: 38133921.
Jain IH, Zazzeron L, et al. Hypoxia as a therapy for mitochondrial disease. Science. 2016 Apr 1;352(6281):54-61. doi: 10.1126/science.aad9642. Epub 2016 Feb 25. PMID: 26917594; PMCID: PMC4860742.
Sharp WW, Beiser DG. Hands free pulse checks: The future of CPR. Resuscitation. 2024 Feb;195:110121. doi: 10.1016/j.resuscitation.2024.110121. Epub 2024 Jan 24. PMID: 38272387.
Couper K, Ji C, et al. Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3). Resusc Plus. 2023 Dec 30;17:100544. doi: 10.1016/j.resplu.2023.100544. PMID: 38260121; PMCID: PMC10801302.
Meilandt C, et al. Intravenous vs. intraosseous vascular access during out-of-hospital cardiac arrest - protocol for a randomised clinical trial. Resusc Plus. 2023 Jul 14;15:100428. doi: 10.1016/j.resplu.2023.100428. PMID: 37502742; PMCID: PMC10368931.

Targeting Mitochondrial Injury: The Future of Post-Cardiac Arrest Resuscitation Care - TMED 801

Share this article

Targeting Mitochondrial Injury: The Future of Post-Cardiac Arrest Resuscitation Care - TMED 801

Recent News and Events