Michael Manning, MD, PhD, Assistant Professor in the Division of Cardiothoracic Anesthesiology, has been awarded a two-year, $150,000 International Anesthesia Research Society (IARS) 2015 Mentored Research Award for his project entitled, “Mechanisms In the Development of Post Operative Atrial Fibrillation.”
Postoperative atrial fibrillation (POAF) occurs in 40%-60% of patients and is the most common complication following cardiac surgery; it is associated with increased length of stay, stroke, and both short- and long-term mortality. While some moderately effective treatments for POAF are available, there are no prevention strategies. Given the aging population and the related increase in cardiac surgeries, development of prevention strategies is necessary to reduce the impact of POAF.
A key factor in POAF development may be inflammation. The exact mechanism by which inflammation influences POAF is unknown, however, one potential mediator is angiotensin II (AngII). Following acute myocardial infarction, local production of AngII as part of the local inflammatory response has been shown to induce atrial remodeling and shorten the atrial effective refractory period. Blocking AngII signaling with angiotensin receptor blockers decreases inflammation-related damage after myocardial infarction. Although multiple similarities exist between the inflammatory processes of acute myocardial infarction and cardiac surgery, it has not been directly evaluated in postoperative inflammation or as a factor in POAF.
The central hypothesis is AngII is produced within the myocardium in association with CPB and ischemia/reperfusion (CPB-I/R), and triggers the pro-inflammatory and pro-fibrotic arrhythmogenic mechanisms underlying the acute development of POAF following cardiac surgery. Using both animal and human studies, Dr. Manning will focus on the mechanism of AngII production during CPB and the role of AngII in perioperative cardiac inflammation while determining whether AngII functions as a primary modulator or secondary regulator in the inflammatory cascade leading to POAF. The objective of these studies is to deconstruct the major cellular contributors of inflammation and identify pharmacologically modifiable points in the pathway to allow new interventions to prevent POAF and improve patient outcomes. Mihai Podgoreanu, MD, Associate Professor with tenure, Division Chief of Cardiothoracic Anesthesiology, will be mentoring Dr. Manning during this project.