Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts

Abstract

In the present study, we tested the reliability of measurements of pressure-volume area (PVA) and oxygen consumption (MV̇o₂) in ex vivo mouse hearts, combining the use of a miniaturized conductance catheter and a fiber-optic oxygen sensor. Second, we tested whether we could reproduce the influence of increased myocardial fatty acid (FA) metabolism on cardiac efficiency in the isolated working mouse heart model, which has already been documented in large animal models. The hearts were perfused with crystalloid buffer containing 11 mM glucose and two different concentrations of FA bound to 3% BSA. The initial concentration was 0.3 ± 0.1 mM, which was subsequently raised to 0.9 ± 0.1 mM. End-systolic and end-diastolic pressure-volume relationships were assessed by temporarily occluding the preload line. Different steady-state PVA-MV̇o₂relationships were obtained by changing the loading conditions (pre- and afterload) of the heart. There were no apparent changes in baseline cardiac performance or contractile efficiency (slope of the PVA-MV̇o₂regression line) in response to the elevation of the perfusate FA concentration. However, all hearts ( n = 8) showed an increase in the y-intercept of the PVA-MV̇o₂regression line after elevation of the palmitate concentration, indicating an FA-induced increase in the unloaded MV̇o₂. Therefore, in the present model, unloaded MV̇o₂is not independent of metabolic substrate. This is, to our knowledge, the first report of a PVA-MV̇o₂relationship in ex vivo perfused murine hearts, using a pressure-volume catheter. The methodology can be an important tool for phenotypic assessment of the relationship among metabolism, contractile performance, and cardiac efficiency in various mouse models.