John Whittle, MD
Duke University Medical Center
Assistant Professor, Honorary Associate Professor in Perioperative Medicine
Durham, NC

Preoperative exercise to improve vagal tone (PREVENT) study

Post-operative morbidity is a significant public health burden and is associated with reduced quality of life and mortality. 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 an established inflammatory phenotype, mitochondrial dysfunction and an increased risk of intraoperative and perioperative morbidity. Aerobic exercise training can improve parasympathetic function in older and multimorbid patients and is a promising non-invasive intervention to reduce perioperative risk. We will employ an effective four- week supervised preoperative aerobic exercise training protocol in older surgical patients listed for major abdominal surgery. Using established laboratory techniques, we will assess baseline and post-intervention parasympathetic autonomic function, aerobic exercise capacity, inflammatory biomarkers and markers of cellular 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. This project is of direct relevance to the field of anesthesiology by addressing the modification of an underexplored mechanistic pathway (autonomic dysfunction) for the development of postoperative complications.