Abstract

Arctic Ground Squirrels (AGS) are resistant to myocardial ischemia/reperfusion (IR) injury when compared to Brown Norway (BN) rats. Intralipid (IL) provides additional species-dependent cardioprotection. We hypothesized that this endogenous and exogenous cardioprotection in AGS is due to higher lipids levels. Samples from 17 AGS and 41 BNs, as well as IL, underwent mass spectrometry for lipid profiling. Each of the >1800 obtained lipid types were compared between species and to IL. The distribution of 64% of all lipids was identical between AGS and BN, 19% were higher in AGS vs 17% in BN. Compared to IL, AGS had 66%, 5% and 29%, and BN 76%, 2% and 22% of all lipids at the same, higher or lower levels, respectively. Several groups were markedly increased in both AGS and IL vs BN: phosphatidyl(P)cholines, lyso-P-ethanolamines(E), PEs, and ether-linked PEs by 1.5/4.5, 2.1/17.0, 8.3/136.9, and 1.3/28.7 times, respectively. Better cardioprotection in AGS under non-hibernating conditions suggests that other endogenous metabolic and/or signaling mechanisms may play a role. The largely improved outcome in IL-perfused AGS vs BN hearts challenges the paradigm of increased glucose and decreased lipid metabolism as beneficial during IR. Thus, the role of metabolism of specific endogenous and/or exogenously supplied lipids and their signaling in cardioprotection warrant further investigation. Supported by VA (CARA-026-10F), NSF, NIH and USAMRMC.

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