Boston - American Association for Thoracic Surgery

89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSL4. Atorvastatin at Reperfusion Reduces Myocardial Infarct Sizein Mice by Activating eNOS of Bone Marrow-Derived CellsZequan Yang, 1 Gorav Ailawadi, 1† Joel Linden, 2 Brent A. French, 3 Irving L. Kron 1*1. Surgery, University of Virginia Health System, Charlottesville, VA, USA;2. Medicine, University of Virginia Health System, Charlottesville, VA, USA;3. Biomedical Engineering, University of Virginia Health System, Charlottesville,VA, USAOBJECTIVE: Myocardial injury occurs after cardiac surgery despite optimal myocardialprotective strategy. Recently, clinical and experimental studies indicate thatthe advantage of early statin use after acute coronary syndromes is independent ofbaseline levels of cholesterol. We hypothesized that atorvastatin could reduce infarctsize in intact mice by activation of eNOS, specifically the eNOS on bone marrowderivedcells.METHODS: C57BL/6J mice (B6) and congenic eNOS knockout (KO) miceunderwent 45 min LAD occlusion and 60 min reperfusion. Chimeric mice, createdby bone marrow transplantation to post-irradiation mice between B6 and eNOSKO mice, underwent 40 min LAD occlusion and 60 min reperfusion. Mice weretreated either with vehicle or atorvastatin in 5% ethanol at a dose of 10 mg/kg IV 5min before initiating reperfusion. Infarct size was evaluated by TTC and Phthaloblue staining.RESULTS: In B6 and eNOS KO mice, risk regions (RR, % of LV mass) were comparableamong the four study groups. In vehicle-control B6 mice, post-ischemicreperfusion resulted in an infarct size of 62 ± 2% of RR. Atorvastatin treatmentcaused a 19% decrease in infarct size in B6 mice (vs. vehicle control, p < 0.05). IneNOS KO vehicle-control mice, infarct size was comparable to that of B6 vehiclecontrolmice (65 ± 2 vs. 62 ± 2%, p = NS). Atorvastatin treatment had no effect oninfarct size in eNOS KO mice (vs. eNOS KO vehicle-control, p = NS). In chimeras,Atorvastatin significantly reduced infarct size in B6/B6 (donor/recipient) mice andB6/KO mice, but not in KO/KO mice or KO/B6 mice (see figure).* AATS Member† Resident Traveling Fellowship 200660