When the close relationship between function and substrate metabolism in ex vivo working mouse hearts goes beyond differences in genetic background

Abstract

Transgenic mice are valuable study model for cardiovascular research. The choice of appropriate control is, however, crucial given the impact of mouse genetic background on various parameters, including cardiac function. In this study, we tested for a link between the cardiac functional and metabolic phenotype of 5 different mouse strains (Bl6J, Bl6CR, SJL, 129SV and ATX). We used our model of working hearts perfused ex vivo with physiological concentrations of 13C‐labeled carbohydrates (CHO) and fatty acids (FA) to assess flux through energy producing pathways. Results reveal marked differences in most functional and metabolic flux parameters measured amongst all control strains. Most striking was the 129SV heart, which showed a better ex vivo function and a shift from FA to glucose oxidation. Beyond all these variations, we found significant correlations between specific metabolic flux and functional parameters, suggesting the role of i) glycolysis as a determinant of cardiac work (cardiac power: r=0.54; dP/dtmax; contractility: r=0.43), ii) CHO oxidation of heart rate (r=0.51) and stroke volume (r=−0.72), and iii) FA oxidation of MVO2 (r=0.70) and coronary flow (r=0.64). Our results highlight a close link between specific functional and metabolic flux parameters in mouse hearts, which goes beyond differences in genetic background and ought to be considered for data interpretation. Supported by the CIHR.