Congratulations to Joern Karhausen, MD, Assistant Professor in the Cardiac Division of Anesthesiology who has been awarded a three-year, $231,000 Mid-Atlantic Affiliate Winter 2015 Scientist Development Grant from the American Heart Association (AHA) entitled, “Platelets as regulators of inflammation and tissue injury after cardiac surgery.”
Platelet activation is a prominent event during cardiac surgery and previous works have shown that blunting platelet responses can improve perioperative outcomes. Based on strong preliminary data, Dr. Karhausen proposes that platelets can initiate inflammatory responses within the small vessels embedded in organ tissues. Specifically, Dr. Karhausen provides, for the first time, evidence that platelets directly activate perivascular mast cells, a cell type known to rapidly launch powerful inflammatory and tissue injurious responses (e.g., in asthma or anaphylaxis). The hypothesis is that platelets and mast cells work together to propagate inflammation and tissue injury, and that modifying this interaction provides a unique opportunity to improve organ protection during cardiac surgery. In their experiments, the investigators will define platelet/mast cell interactions by in vivo imaging of the microvascular interface and fluorescent labeled platelets and mast cells. Next, they aim to identify the mast cell-activating platelet factor(s) by combining state of the art proteomic analysis of the platelet secretome with comprehensive testing of mast cell responses. Lastly, the investigators will pursue the strong translational opportunities of the proposed mechanism by characterizing the impact of modifying mast cell and platelet responses on the inflammatory and tissue injurious responses observed in a pre-clinical model of cardiopulmonary bypass circulation and circulatory arrest. A team of experts in the fields of mast cell (Dr. Soman Abraham, Dept. of Pathology), animal models of cardiopulmonary bypass (Dr. Ma Qing, Anesthesiology), and clinical statistics and epidemiology (Dr. Miklos Kertai, Anesthesiology) provide strong support for successful completion.