Trening og energistoffskifte
Heart failure (HF) impairs resting myocardial energetics and exercise training is included in most rehabilitation programs and benefits HF patients. The aim of this study was to investigate the effects of exercise training at different intensities in HF rats. In this study, we firstly used rats underwent myocardial infarctions or sham operations and were separated into three exercise groups: sedentary control, moderate intensity, or high intensity. The impact of HF and exercise training on energy metabolism was evaluated by 31P MRS and mitochondrial respirometry. The concentrations of key bioenergetic metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified by MRS. VO2max was measured by treadmill respirometry. From the methodology, we obtained the data from whole body oxygen consumption test, in vitro MR spectroscopy and in situ mitochondrial function. In summary, our study investigated the effect of different exercise training intensities on energy metabolism in HF. Heart failure induced a significant reduction in PCr/ATP ratio, the clinically examined biomarker of heart failure, in our HF rat models. This reduction was induced by decreased level of PCr with unchanged ATP levels. As we hypothesized, the energy metabolism was impaired in HF rats and could be recovered after exercise training. This is reflected in relatively increased ATP level. Furthermore, the reduced mitochondrial respiratory capacity in HF rats was partially recovered by high-intensity exercise training, through increased complex I respiration. These adaptations were associated with an improvement in VO2max and running capacity. The experimental rat model mimics human physiology and helps us to further understand the mechanism of cardiac performance improvement by exercise training. Taken together, our results show that the repressed PCr levels in MI hearts may not be crucial to exercise adaptation. Exercise training in our HF rat model resulted in significant improvement in exercise capacity, and modulated mitochondrial function, VO2max, and ATP availability through mitochondrial respiration. These findings support the hypothesis that exercise training could have potentially important implications in clinical treatment for patients with HF. Considering the close association between ATP and PCr transfer, the molecular mechanism in which unchanged PCr and increased ATP synthesis could improve energy metabolism post exercise training remains to be investigated.
Information on energy metabolism from magnetic resonance spectroscopy may reveal important details of heart muscle function. The aim of the present project is to determine whether magnetic resonance spectroscopy (MRS) can be used to evaluate the function of the heart muscle. Previous studies have shown that reduced heart muscle function in heart failure is associated with impaired energy metabolism in the heart, and that this can be detected noninvasively by this method. We have already shown that exercise training improves heart muscle function in heart failure. Therefore, the working hypothesis of the present PhD project was that exercise training improves cardiac function and partially restores myocardial energy metabolism. If this is the case, then in vivo MRS could be used as a noninvasive method to evaluate the effects of training and other treatments in heart failure patients. The project started in May 2015, and the first part was to determine the changes in energy metabolism in an experimental model of heart failure and exercise training in rats. Analysis of tissue samples from the heart muscle showed that myocardial infarction and exercise training influenced the level of two high-energy phosphor metabolites (phosphocreatine and adenosine triphosphate). It is likely that these changes resulted from reduced mitochondrial function, which is a central part of energy metabolism. These early results have been reported in a manuscript that has been submitted to the Journal of Applied physiology. The next part of the project will be to test out whether we are able to detect similar changes using noninvasive MRS measurements in the same model. Even if there is still much work to do, the project is proceeding according to plan.