Analysis of metabolic remodeling and mitochondrial function in heart failure

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Although mitochondria play pivotal roles in heart failure, there are few feasible methods for cardiac assessing mitochondrial function in vivo. We validated that the retention of technetium-99m sestamibi (99mTc-MIBI) is useful for assessing cardiac mitochondrial function in vivo and that increased washout (or decreased retention) of 99mTc-MIBI occurs in an animal model of HF and patients with HF, associated with the severity of the disease.Next, we examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function. The uptake of analogs of glucose or fatty acids and the phosphocreatine/ATP ratio at rest were normal. The levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered, and the capacity of mitochondrial function was decreased.