Funding: NIH K08NS069817 (Project period: 9/15/10 to 8/31/15)
Dr. Dezfulian is an adult and pediatric critical care physician acutely aware of the paucity of post-resuscitation therapies for the cardiac arrest survivors he cares for. This career development award supplements his research background with senior mentorship and lab-based and didactic training in neurosciences and redox signaling. The research plan is based on preliminary observations which support the hypothesis that nitrite-mediated neuroprotection after cardiac arrest occurs through nitric oxide (NO) and S-nitrosothiol (S-NO)-based signaling that prevents subsequent signaled neuronal death and mitochondrial dysfunction. This hypothesis will be tested along three aims: (1) to define the optimal nitrite dose and timing and quantify the relative contributions of NO- and S-NO based signaling in neuroprotection, (2) to test whether nitrite-mediated neuroprotection results from nitrosylation of critical cell survival signals, and (3) to test whether nitrite-mediated NO and S-NO production effects mitochondrial function and prevents apoptosis.