Abstract 1137: Effects of Ischemic Preconditioning on Fatty Acid Oxidation at the Sub-Acute Stage After Reperfusion in the Rat Heart
Background: Ischemic preconditioning (IP) is known to have cardioprotective action against following sustained ischemia and reduce the accumulation of long-chain fatty acid (FA) CoA that might be deleterious to cardiac energy metabolism and electrical stability. However, it remains unclear whether IP might affect FA oxidation late after reperfusion in an in situ heart. Accordingly, we investigated the influences of IP on myocardial ischemia-reperfusion (MI-R) injury and FA metabolism including FA oxidation and myocardial accumulation of long-chain FA CoA at the sub-acute stage after reperfusion.
Methods: (1) Determination of infarct size: MI-R was induced by coronary artery occlusion for 30 min followed by 2-hr reperfusion. IP was achieved with 5-min ischemia followed by 5-min reperfusion before MI-R. (2) FA metabolism: Using a tracer of 131I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), myocar-dial FA metabolism with or without the pretreatment of PC was assessed 3 days after reperfusion following 15-min ischemia to avoid the occurrence of myocardial necrosis by the sustained ischemia. FA oxidation was determined by a thin-layer chromatography.
Results: Infarct size was smaller in PC (n=6) than in control MI-R (CON, n=8) (13±8 vs 48±15%, p<0.01). In CON rats (n=7), myocardial 9MPA accumulation was reduced in ischemic region (IR) as compared to non-IR (0.38±0.13 vs 0.53±0.15 %kg dose/g, p<0.01), but the non-metabolized 9MPA fraction was greater in the IR (n=8, 60±13 vs 56±13%, p<0.05). In IR of PC rats, however, the reduction of 9MPA accumulation was attenuated (n=9, 0.43±0.13 %kg dose/g) and increases in the non-metabolized 9MPA fraction was suppressed (n=8, 57±6%). The final product of 9MPA processed by α- and β-oxidation was greater in PC than in CON in both IR (17±7 vs 8±5%, p<0.05) and non-IR (19±5 vs 8±4%, p<0.05).
Conclusion: PC inhibited the accumulation of non-metabolized FA fraction, namely, long-chain FA CoA, and accelerated FA oxidation in a rat heart. These alterations in FA metabolism induced by PC may partially contribute to its infarct-limiting effect or a quick recovery from myocardial stunning.