From the Laboratory… to Better Cardiac Arrest Treatment

Each year more than 605,000 Americans suffer cardiac arrest, and despite improved cardiopulmonary resuscitation (CPR), post-resuscitation therapy and cardiovascular support, overall outcomes remain poor. Post-cardiac arrest syndrome occurs after resuscitation, causing widespread organ injury, especially to the brain and heart. It is characterized by development of systemic inflammatory response, which contributes to additional organ damage.

A Relationship Starts and Research Takes Off

Sergey Ryzhov, PhD, MD, MaineHealth Institute for Research (MHIR) faculty scientist, and David Seder, MD, Critical Care physician, have a long-standing collaboration. For over nine years, they have been working together to investigate the role of inflammation after cardiac arrest and how those differences result in different outcomes, seamlessly connecting research to patient care.

This work includes identifying protective pathways that would allow immunomodulatory approaches to improve post-cardiac arrest care. Immunomodulatory approaches or immunotherapy is the treatment of disease by activating or suppressing the immune system.

Supporting Translational Science at MaineHealth

The fusion of basic research with clinical practice is also known as translational science, a field of research that aims to translate scientific discoveries from the laboratory into practical applications that improve human health.

The Foundations of Future Work

“We’re lucky to have a dedicated team on both the basic science and clinical sides,” said Sergey Ryzhov, PhD, MD. “Our basic science team developed a mouse cardiac arrest model, which is the foundation for our future work. Meanwhile, our clinical team has enrolled several hundred patients over the years. This collaboration has been my dream, to fuse basic research with clinical practice.”

Grant Funding Bridges Knowledge Gap

In April of 2024, Drs. Ryzhov and Seder received a $3 million National Institutes of Health (NIH) R01 grant to further their work. This funding is being used to determine the role of CD73 (an enzyme found on the surface of many cells in the body) in the protection against excessive inflammation and secondary heart and brain tissue damage after cardiac arrest.

With over eight years of sample collection, the team is ready to take a deeper dive into what mechanisms modulate the immune response after cardiac arrest.  They will take their patient observation data gathered in clinical settings and use them in the lab with mouse models. CD73 is a key enzyme in the generation of adenosine, a type of molecule characterized by potent anti-inflammatory properties. If their hypothesis is correct, these findings will be used to develop clinical trials that test which therapies help regulate adenosine in patients recovering after cardiac arrest.

“I am looking forward most to finding meaningful scientific results that we can turn into practical treatments for our patients.”

–Dave Seder, MD

Promise for Cardiac Arrest Treatment & More

For a long time, the physical connection of white blood cells (monocytes and lymphocytes) and tissue inflammation were ignored in the recovery of the cardiac arrest population. It appears they come together to form biologically active complexes, and Drs. Ryzhov and Seder believe these complexes have a protective role in the brain and heart, by modulating the inflammatory responses.

“This is a novel idea that has not been looked at in the cardiac arrest population – specifically how the immune system either damages or repairs organs after an arrest – our aim is to work out these mechanisms,” said Dr. Seder.

This research also applies to other diseases, like acute lung injury and sepsis.  Even though this work is most promising in cardiac arrest, the underlying biology also applies to other diseases as well – happy coincidence and an opportunity to help patients with a wide range of problems.

National Institutes of Health (NIH) R01 Grant

The NIH R01 is the “gold standard” of research grants awarded by the National Institutes of Health. It is generally a five-year grant in the range of $250,000 – $500,000 direct costs per year and is an investigator-initiated research project addressing a biomedical question that can be basic, translational or clinical research. The five years gives the researcher time needed to achieve publishable results. R01s are highly competitive; roughly 19% of R01s are funded by NIH each year. MHIR investigators currently hold a total of 14 R01s. The R01 is evaluated through a rigorous peer review process which scores research design, significance of the problem, institutional environment, and investigator’s record. MHIR’s track record in obtaining R01s reflects a rich scientific and academic environment at MaineHealth that provides the resources, research infrastructure, and intellectual support for investigator success.