Abstract 336: Critical Level of Intramyocardial Lipid Impairs Transmural Principal Strains in Hearts of Low Overexpressing PPARalpha Mice Due to High Fat Diet
Intramyocadial lipid accumulation precedes some cardiomyopathies, but little information is known of direct, short term effects on cardiac mechanics. Thus, we tested the hypothesis that intramyocardial lipid accumulation, during high fat diet, affects wall mechanics and stiffness in the left ventricle (LV) of hearts in nontransgenic mice and transgenic mice predisposed to elevated triacylglyceride (TG) storage due to low-overexpression of PPARalpha. Myocardial lipid and transmural, 2-D principal strains were determined by in vivo MRS/MRI (14.1 T) before and after 2 weeks of high fat diet (HF) in anesthetized, MHC-PPARalpha (PPARa, n=17) and nontransgenic littermate (NTG, n=19) mice (age 5 months). 1H MRS of acyl-chain methylene groups in LV septum at midbase (1×1×1mm3), provided in vivo mobile lipid content relative to water. End-point in vitro assays of TAG were performed on frozen LV. Cardiac MRI tagging (0.3mm × 0.3mm) at midbase, provided transmural E1 (stretch) and E2 (compression) strains in epi- and endo-cardium of the same LV septal region as for MRS. Heart rates during MRS/MRI in all mice ranged 400–590 bpm. With HF, mobile lipid increased 133% in NTG and 88% PPARa (P<0.05), but PPARa displayed higher lipid than NTG before and after HF. After HF, PPARa had higher lipid and TAG than NTG, by 125% and 67%, respectively. With HF, E1 and E2 dropped in both epi- and endocardium of PPARa, but strains in NTG were unaffected (Table⇓). Lipid content correlated negatively to the magnitudes of endocardial E1 (r=−0.76) and E2 (r=−0.78) in all hearts (P<0.05). As a consequence of increased dietary fat, reduced strains resulted from either mechanical effects of lipid infiltration on myocardial elasticity and/or biochemical affects of acyl-derivatives on myofilaments. NTG never attained lipid levels as high as PPARa in which strains were reduced, suggesting a threshold, or critical lipid content, affects LV wall function.