Heart failure (HF) is a global term for the physiological state where the volume of blood pumped by the heart is insufficient in meeting the needs of the body. Although there is an agreement that advanced HF is characterized by metabolic abnormalities, studies conflict about the nature of these defects. Whole human hearts were procured from two separate patient groups at the time of orthotopic heart transplantation; non-failing brain dead organ donors with no history of heart failure, and end stage HF heart transplant patients. The patients were selected upon the following criteria; the absence of a history of heart failure in the non-failing (NF) control cohort (n=8), and the presence of HF in the cases (n=8). After snap frozen heart tissue (around 50 mg of dry tissue) where homogenized in ice cold buffer the tissue samples underwent extraction by a modified Folch procedure, the organic phase was concentrated and analyzed by high-resolution nanospray ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Two different software platforms (SIEVE 2.0-Thermo and XCMS- Scripps) were used to analyze the data.  Pair-wise comparison of the HF cases with the NF controls revealed more than a thousand dysregulated features. Initial identification of the features was accomplished through accurate mass database searching. The vast majority of species were found to be decreased in HF as compared to NF. This approach led to the identification of several carnitines and others classes of lipids, including ceramides, phospholipids, and triglycerides. Selected dyregulated molecules were quantified by stable isotope dilution with a chemically similar internal standard. Final identification was done by comparison with authentic standards acquired commercially and/or by total synthesis.

Metabolomics of heart failure

248th National Meeting (2014)

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