BACKGROUND: Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure. MATERIALS AND METHODS: The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides. RESULTS: Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy. CONCLUSION: Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.
BACKGROUND: Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure. MATERIALS AND METHODS: The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides. RESULTS: Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy. CONCLUSION: Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.
Authors: Aslan T Turer; Craig R Malloy; Christopher B Newgard; Mihai V Podgoreanu Journal: Curr Opin Clin Nutr Metab Care Date: 2010-07 Impact factor: 4.294
Authors: Andrea M Cordero-Reyes; Anisha A Gupte; Keith A Youker; Matthias Loebe; Willa A Hsueh; Guillermo Torre-Amione; Heinrich Taegtmeyer; Dale J Hamilton Journal: J Mol Cell Cardiol Date: 2014-01-09 Impact factor: 5.000
Authors: Jianru Shi; Wangde Dai; Sharon L Hale; David A Brown; Miao Wang; Xianlin Han; Robert A Kloner Journal: Life Sci Date: 2015-10-06 Impact factor: 5.037