2019 DIG Research Project | “Can a Structured Exercise Intervention Modulate the Vagal Inflammatory Response in High-Risk Surgical Patients?”
John Whittle, MB BS, MD (Res), FRCA, FFICM, is an anesthesiology, perioperative medicine and critical care physician-scientist within Duke Anesthesiology at Duke University Medical Center and a member of the department’s General, Vascular and Transplant Anesthesia Division where he practices in perioperative medicine and clinical anesthesiology. He has a specific interest in the high-risk patient presenting for non-cardiac surgery and provides anesthesia services as part of the liver transplant team. Whittle also serves the department’s Critical Care Medicine Division where he practices as an intensivist in the Surgical Intensive Care Unit at Duke University Hospital. Additionally, he is a fellow of the Royal College of Anaesthetists and the Faculty of Intensive Care Medicine in the United Kingdom.
Whittle is originally from the United Kingdom. As an undergraduate, he attended King’s College London where he earned a degree in aerospace physiology. He first participated in research where he studied the feasibility of using oxygen generated from a molecular sieve oxygen generator to supply passenger drop down masks on civilian and military aircraft. His subsequent work included aiding with the design and testing of an arterialized earlobe blood collector for use in microgravity, which he was able to test at the European Space Agency in a parabolic flight campaign. As a clinical medical student at King’s, Whittle was awarded a scholarship for excellence in basic sciences as well as a university prize for exam performance and the International Journal of Surgery’s Howard Ellis prize for best research paper of the year. He embarked on post graduate training in anesthesia and intensive care medicine in the Central London School of Anaesthesia, based around University College London (UCL) during which he earned fellowship of the Royal College of Anaesthetists and of the Faculty of Intensive Care Medicine. During his training, he was awarded a two-year National Institute for Health Research Academic Clinical Fellowship, which he carried out at UCL. This fellowship, alongside his clinical training, sparked an abiding and strong interest in the use of translational research methodology to understand and ultimately improve the outcomes of high-risk patients undergoing major surgery.
Whittle continued his academic training at UCL with two years of combined intensive care and academic training with the Health Care America Fellowship, completing his Doctor of Medicine (research) thesis on the subject of perioperative autonomic dysfunction; this research resulted in several peer reviewed publications, as well as the award of a research prize by the London Academy of Anaesthesia. He then completed an additional fellowship in perioperative medicine at UCL where he was involved in the development and implantation of a novel perioperative care model for the high-risk surgical patient. Following award of his certificate of completion of training and specialist registration with the General Medical Council (UK), Whittle worked as a consultant in anaesthesia and perioperative medicine at the Royal Free Hospital prior to moving to Duke to continue to develop his research and clinical interests.
Whittle’s research interests involve investigating strategies to reduce perioperative risk in high-risk patients undergoing major surgery. Specifically, he is interested in modulating the autonomic nervous system to optimize immune and bioenergetic pathways with a view to preventing or blunting perioperative organ injury. Whittle’s current research uses exercise training in the preoperative period to improve aerobic fitness, a clear correlate with perioperative outcome and function of the parasympathetic nervous system. He aims to explore the impact of improving parasympathetic function on the ability of the body to use oxygen and defend itself from the trauma of surgery.
DREAM Innovation Grants (DIG) support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management research and are made possible through Duke Anesthesiology’s Duke DREAM Campaign. Whittle is excited to have received a 2019 DIG to further pursue studies examining the role of low exercise capacity and parasympathetic function in surgical outcome. Impaired preoperative aerobic exercise capacity is strongly associated with established inflammation, an increased inflammatory response to surgical trauma, mitochondrial dysfunction and the development of postoperative complications. The mechanisms underlying these associations are not currently established. Parasympathetic autonomic dysfunction (PAD) is one potential unifying mechanism for these relationships. PAD is common in aerobically-unfit individuals and in older surgical patients. It is associated with established inflammation, mitochondrial dysfunction and an increased risk of perioperative complications. Aerobic exercise training can improve parasympathetic function in older and multimorbid patients and is a promising non-invasive intervention to reduce perioperative risk. He will employ a four- week supervised preoperative aerobic exercise training protocol in older surgical patients listed for major abdominal surgery. Using established laboratory techniques, Whittle will assess baseline and post-intervention parasympathetic autonomic function, aerobic exercise capacity, inflammatory biomarkers and markers of mitochondrial function in anticipation of a greater understanding of mechanisms underlying the development of perioperative morbidity, and in anticipation of the development of strategies to enhance perioperative organ protection through the modulation of parasympathetic activity.
He will conduct his studies under the mentorship of Dr. William Maixner, an expert on autonomic function and head of Duke Anesthesiology’s Center for Perioperative Organ Protection, and Dr. Paul Wischmeyer, a critical care physician-scientist with expertise in preoperative assessment and optimization of the high-risk surgical patient. Collaborators include: Dr. David MacLeod, director of Duke’s Human Physiology and Pharmacology Laboratory, Dr. Amy Pastva, who has extensive experience of how rehabilitative strategies influence mechanisms to improve patient outcomes, Dr. Raquel Bartz, chief of the Critical Care Medicine Division at Duke with a strong background in mitochondrial research, and Dr. Brant Inman, a urological surgeon with a strong background in immune therapies for cancer and trials in surgical patients.
These awarded DIG funds are expected to underpin the development of novel therapies designed to improve autonomic function, which will have a significantly positive impact on perioperative and critically ill patients. They will also provide seed funding to collect preliminary data for future grant applications that will allow Whittle to establish himself as an independent investigator.