Abstract 12284: Second Window of Ischemic Preconditioning Normalizes the Contribution of Long Chain Fatty Acids to β-Oxidation during Coronary Stenosis
A major mechanism by which the heart can induce protection is by altering metabolism. Whereas preconditioning is the most powerful mechanism mediating ischemic cardioprotection, little is known regarding the metabolic changes involved. We examined the effects of the second window of preconditioning (SWOP) on long chain fatty acid (LCFA) oxidation in chronically instrumented, conscious pigs: 1) normal baseline perfusion (CON, n=5), 2) coronary artery stenosis (STEN, n=5), and 3) coronary artery stenosis 24 hr following preconditioning, (SWOP+STEN, n=6). Myocardial ischemia was induced by a LAD stenosis (40% flow reduction) for 90 minutes in STEN and SWOP+STEN pigs. Long chain fatty acid (LCFA) oxidation was assessed by infusing [2,4,6,8,10,12,14,16–13C8]-palmitate (blood concentration = 0.4 mmol/L, 40 minutes) into the LAD during control perfusion (CON) or the final 40 minutes of stenosis (STEN and SWOP+STEN). 13C NMR of extracts from frozen epi- (EPI) and endocardium (ENDO) indicated the fraction of palmitate entering β-oxidation by mitochondria. With STEN, blood flow was reduced in ENDO, but not EPI, of both STEN and SWOP+STEN. Wall thickening was less severely reduced in SWOP+STEN (−51±3%) than STEN (−64±3%, P<0.05). Hypoperfusion in STEN dropped the contribution of palmitate by 29% in EPI and 52% in ENDO, and increased accumulation of glycolytic end products (lactate and alanine). In contrast, SWOP normalized the contribution of palmitate (SWOP+STEN: EPI = 0.26±0.03, ENDO = 0.22±0.03, CON: EPI = 0.24±0.03, ENDO = 0.27±0.04), despite elevated glycolytic end products. ENDO malonyl-CoA content was similar in SWOP+STEN (0.95±0.07 nmol/g) and CON (0.99±0.07), but lowered in STEN (0.32±0.05), corresponding to the extent of palmitate entry into β-oxidation. Thus, SWOP enhanced regional wall function as previously shown, but also induced normal contributions of LCFA to oxidative metabolism. Thus, SWOP restores β-oxidation of LCFA during LAD stenosis despite the presence of both reduced regional blood flow and increased anaerobic glycolysis. The findings indicate that factors other than blood flow and tissue oxygenation regulate LCFA metabolism in hypoperfused myocardium and that LCFA oxidation supports the enhanced function afforded by SWOP.
- © 2010 by American Heart Association, Inc.