The Foundation for Anesthesia Education and Research has awarded Duke Anesthesiology’s Quintin Quinones, MD, PhD, a two-year, $175,000 mentored research training grant, titled “Reversible Immunomodulation as a Strategy for Ischemia Tolerance in Hibernation.” His mentor for this grant is Dr. Mihai Podgoreanu, chief of the Cardiothoracic Anesthesia Division.
During surgery or critical illness, patients sometimes suffer organ dysfunction related to uncontrolled inflammation. There are currently no drugs that effectively treat this problem. To work towards new treatments, Dr. Quinones and a team of investigators have developed a surgical model to study a hibernating mammal known as the arctic ground squirrel (AGS). These animals show a remarkable, natural resistance to injury in a robust surgical model that closely mirrors what humans experience during major heart surgery. To understand how arctic ground squirrels are different, they’re comparing them to rats in the same surgical model; rats do not show any natural resistance and suffer organ dysfunction much in the way that humans do.
The focus of the study is a unique trait found in hibernators – the AGS can regulate its innate immune system to decrease inflammation following surgical injury. Dr. Quinones and his co-investigators will examine protein levels and the function of white blood cells in the AGS vs. the rat. They will also look at protein levels in human white blood cells. By understanding how the AGS is able to regulate its innate immune system, they hope to identify potential targets that will lead to treatments for human patients during surgery and critical illness.
There is a fundamental knowledge gap regarding the role of innate immunity in injury during ischemia and reperfusion in the perioperative period and during critical illness. Hibernating mammals enjoy natural resistance to ischemia/reperfusion injury as a result of adaptations that allow them to survive winter torpor-arousal cycles without injury. One such adaptation is natural reversible modulation of innate immunity that reduces responses to danger-associated molecular patterns and pathogen-associated molecular patterns. A comparative biology approach provides the opportunity to study animals that are naturally adapted to survive ischemia and reperfusion. Dr. Quinones hypothesizes that hibernator resistance to ischemia/reperfusion is secondary to reversible modulation of innate immunity.
Dr. Quinones is an assistant professor of anesthesiology in the department’s Cardiothoracic Anesthesia Division. His research on hibernation biology has been featured in several publications, including the journal, Anesthesiology (June 2016), as well as the 2016 edition and 2013 edition of Duke Anesthesiology’s annual BluePrint magazine.