Abstract 16377: Long-Term Treatment with Eicosapentaenoic Acid Ameliorates Myocardial Ischemia-Reperfusion Injury in Pigs in vivo. -A Potential Role of Rho-kinase Pathway-
Background: Epidemiological studies have suggested that eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, may exert cardioprotective effects against ischemic heart disease; however, the detailed mechanisms remain to be elucidated. Rho-kinase, the effectors of the small GTP-binding protein Rho, plays an important role in the pathogenesis of cardiovascular diseases including ischemia-reperfusion (I/R) injury. Thus, we tested our hypothesis that long-term EPA treatment ameliorates myocardial I/R injury through inhibition of Rho-kinase pathway in pigs in vivo.
Methods:Male pigs were treated with either a control chow or EPA (600 mg/kg/day, PO) for 3 weeks (n=8 each). They were subjected to myocardial ischemia by 90-min occlusion of the left circumflex coronary artery and subsequent 60-min reperfusion. We confirmed that the membrane EPA level in red blood cells was 4.4±0.3 mol%, a comparable level with that in humans treated with EPA.
Results: Hemodynamic changes during I/R were similar between the two groups. However, the EPA treatment significantly ameliorated myocardial I/R injury, including regional wall motion abnormality (EPA 5.3±3.6 vs. control 35.1±3.8 unit, P<0.0001) and LV ejection fraction (EPA 43±9% vs. control 32±7%, P<0.05), the occurrence of ventricular arrhythmias (EPA 181±73 vs. control 389±51 events, P<0.0001) and histological accumulation of inflammatory cells in ischemic myocardium (EPA 69±34 vs. control 170±107 cells/mm2, P<0.001). Importantly, the EPA treatment significantly inhibited myocardial Rho-kinase activity (assessed by the extent of phosphorylation of myosin-binding subunit) (EPA 0.47±0.11 vs. control 0.77±0.14, P<0.05) with the enhanced expression of eNOS mRNA (EPA 0.56±0.13 vs. control 0.23±0.07, P<0.01) in ischemic myocardium (Figure).
Conclusions: These results indicate that long-term treatment with EPA ameliorates I/R injury through inhibition of Rho-kinase pathway in vivo.
- © 2010 by American Heart Association, Inc.