Effect of exercise training on cardiac metabolism in rats with heart failure

Abstract

Objectives. Heart failure (HF) impairs resting myocardial energetics, myocardial mitochondrial performance, and maximal oxygen uptake (VO_2max). Exercise training is included in most rehabilitation programs and benefits HF patients. However, the effect of exercise intensity on cardiac mitochondrial respiration and concentrations of the key bioenergetic metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi) is unclear. This study aimed to investigate the effects of exercise training at different intensities in rats with HF. Methods. Rats underwent myocardial infarction or sham operations and were divided into three subgroups: sedentary, moderate intensity, or high intensity. The impact of HF and 6 weeks of exercise training on energy metabolism was evaluated by ³¹P magnetic resonance spectroscopy and mitochondrial respirometry. The concentrations of PCr, ATP, and Pi were quantified by magnetic resonance spectroscopy. VO_2max was measured by treadmill respirometry. Results. Exercise training increased VO_2max in sham and HF. PCr/ATP ratio was reduced in HF (p < .01) and remained unchanged by exercise training. PCr concentration was significantly lower in HF compared to sham (p < .01). Moderate and high-intensity exercise training increased ATP in HF and sham. HF impaired complex I (CI) and complex II (p = .034) respiration. High-intensity exercise training recovered CI respiration in HF rats compared to HF sedentary (p = .014). Conclusions. Exercise training improved cardiac performance, as indicated by increased VO_2max and higher exercise capacity, without changing the myocardial PCr/ATP ratio. These observations suggest that the PCr/ATP biomarker is not suited to evaluate the beneficial effects of exercise training in the heart. The exact mechanisms require further investigations, as exercise training did increase ATP levels and CI respiration.

Keywords: 31P MRS; ATP; Myocardial infarction; exercise; high-energy phosphate; magnetic resonance spectroscopy; mitochondrial respirometry; phosphocreatine.