Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Propofol is an anesthetic that has intrinsic anti-oxidant capacity. Our preliminary data indicated that when high dose propofol was administered during surgeries to treat severe coronary disease, this drug conferred cardioprotective effects. Patients given propofol in this novel way had shorter intensive care unit stay and improved cardiac function compared to other treatment groups. Animal and cell culture studies suggested that propofol exerted its cardioprotective effect via an anti-oxidative mechanism. But this speculation hasn't been proven in clinical settings. To answer this question, I plan to work on the following projects: 1) determine the real concentration of propofol achieved in patients; 2) answer if high dose propofol is associated with reduced level of reactive oxygen species; 3) investigate if high dose propofol is related with decreased level of reactive nitrogen species; 4) use oxidative DNA damage products to verify our results; 5) identify and validate what downstream effectors of reduced oxidative stress will rescue cardiac cells. To this point, I have developed a straightforward method to confirm propofol concentration in whole blood. I have also developed plans to assess reactive oxygen species, reactive nitrogen species, and oxidative DNA damage products. But because the plasmas of patients have diverse backgrounds, specific, sensitive and reliable analytical methods are urgently needed for detecting small but relevant differences between treatment groups. Our lab has expertise with capillary electrophoresis, gas chromatography, liquid chromatography and mass spectrometry. These analytical techniques ensured specificity, sensitivity and reliability of the analysis. This translation of contemporary analytical techniques into clinical applications will provide molecular evidences to guide further refinement of clinical maneuvers.