Metabolic and Functional Phenotype of Pathologic Cardiac Hypertrophy in Rodents

Abstract

The metabolic phenotype of pathologic cardiac hypertrophy has been well characterized in rats but not yet in mice. Thus, we set out to determine the metabolic phenotype of pathologic cardiac hypertrophy in mice and compared it to that in rats. Accordingly, function, glycolysis and oxidation of glucose, lactate and palmitate were measured in non-ischemic, normoxic isolated working hypertrophied (H) and control (C) hearts from male SD rats (R) and CD-1 mice (M) with and without abdominal aortic constriction. Similar to that observed in rats, palmitate oxidation (PO) was decreased (28%) and glycolysis (GF) was increased (27%) in pathologically hypertrophied hearts compared to control hearts in mice with no significant change in lactate (LO) or glucose oxidation (GO). In rats, the contribution of palmitate oxidation to ATP production, calculated from rates of substrate utilization, was reduced in hypertrophied hearts while that of GO and GF were increased compared to control hearts. In contrast, only an increased contribution of GF to ATP was observed in hypertrophied hearts in mice. Thus, while the profile of substrate utilization in hypertrophied hearts in mice is similar to that in rats, the relative contribution of catabolic pathways that generate ATP differs between hypertrophied mouse and rat hearts. Table 1:. Hydraulic work per gram wet wt (HW/g) and metabolism (nmol/min/g dry wt)