Abstract 994: Cardioprotection Against Myocardial Infarction by Ischemic Pre- and Post-Conditioning are Both Completely Abrogated by Acute Hyperglycemia

Abstract

Introduction: Acute hyperglycemia (HG) is associated with larger infarct size, impaired cardiac function and increased mortality, independent of diabetes. We hypothesized that the cardioprotective effects of both ischemic pre- and post-conditioning (pre-C & post-C) would be impacted by acute HG. Methods: A total of 37 C57BL/6 mice were assigned to 6 groups. All mice underwent 40 min of LAD occlusion followed by 60 min of reperfusion. Acute HG (~400 mg/dl) was induced in 3 groups with an IP injection of dextrose (2g/kg body weight) given 40 min prior to the start of index ischemia. The ischemic pre-C protocol (2 groups) was 2 cycles of 5 min ischemia and 5 min reperfusion prior to index ischemia. The post-C protocol (2 groups) was 3 cycles of 5 sec reperfusion and 5 sec ischemia following index ischemia. Results: Risk region (RR, % of LV) as determined by Phthalo blue staining was similar among study groups (Fig , p = NS). In euglycemic control mice, infarct size (by TTC staining) without cardioprotection was 51.6 ± 2.0 % of RR (Fig ). Early pre-C reduced infarct size to 25.5 ± 3.7 (a 50% reduction, p < 0.05 vs control) while post-C reduced it to 37.9 ± 0.5 (a 27% reduction, p < 0.05 vs control). In HG mice, infarct size was significantly exacerbated to 63.1 ± 2.9 (a 22% increase, p < 0.05 vs euglycemic controls). Cardioprotection by pre-C was completely abrogated in HG mice (55.9 ± 3.6 of RR, p = NS vs HG controls). Similarly, post-C was completely ineffective in protecting HG mice against infarction (59.4 ± 2.5, p = NS vs HG controls). Conclusion: Acute hyperglycemia in non-diabetic mice completely abolishes the cardioprotective effects of both ischemic pre-C and post-C against myocardial infarction.