Cardiometabolic adaptations to altered fuel supply, Ca2+ handling and exercise

Abstract

The thesis consists of experimental studies elucidating the mechanisms that contribute to changes in cardiac efficiency by i) the increase in fatty acid supply to the heart (chronic and acute), ii) changes in cardiac calcium handling and iii) physical exercise. By measuring the heart's oxygen consumption for both mechanical and non-mechanical processes, we have shown for the first time, that oxygen-cost of basal metabolism and excitation-contraction coupling is increased as a result of an acute high fat supply and a chronic exposure to high fat to the heart (i.e. diabetes). We have also shown that the initiation of oxygen wasting processes in the heart after an acute elevation of fatty acids is due to the presence of fat and not solely due to an increase in fatty acid oxidation in the heart. Furthermore, we have demonstrated in a heart failure model in which calcium handling is altered, that the cardiac oxygen consumption for its mechanical work has increased, while oxygen consumption for non-mechanical processes was reduced. Finally we have demonstrated that exercise can increase the heart's efficiency and substrate utilization if the intensity of the training is high.