Energy metabolism in patients with diabetes and heart failure

2019 ◽  
pp. 32-36
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
High Energy ◽  
Energy Deficit ◽  
Diabetic Patients ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Myocardial Energy Metabolism

The heart has a very high energy demand, which is mostly met by mitochondrial oxidative phosphorylation and, to a lesser extent, by glycolysis. In heart failure, there are substantial alterations in myocardial energy metabolism that lead to an “energy-deficient” state. This includes a marked reduction in overall mitochondrial oxidative phosphorylation and an uncoupling between high glycolysis rates and low glucose oxidation, which together contributes to the energy deficit and deteriorates contractile dysfunction. Cardiac ketone oxidation is also increased in heart failure, although it has yet to be determined whether this is an adaptive or maladaptive alteration. Diabetes is a major risk factor for heart failure development. It induces alterations in myocardial energy metabolism and is often associated with ventricular dysfunction. Similar to heart failure, a major change in myocardial energy metabolism in diabetic patients is a reduction in glucose oxidation, which negatively influences cardiac function. In both heart failure and diabetes, a growing body of evidence suggests that targeting myocardial energy metabolism by optimizing cardiac energy substrate preference could be a potential therapeutic approach to improve patient outcomes.

Barth Syndrome-Related Cardiomyopathy is Associated with a Reduction in Myocardial Glucose Oxidation

2021 ◽  
Author(s):  
Amanda A. Greenwell ◽  
Keshav Gopal ◽  
Tariq Altamimi ◽  
Christina T. Saed ◽  
Faqi Wang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Glucose Oxidation ◽  
Genetic Disorder ◽  
Left Ventricular ◽  
Barth Syndrome ◽  
Acid Oxidation ◽  
Functional Impairments ◽  
Myocardial Energy Metabolism ◽  
Oxidation Rates

Heart failure presents as the leading cause of infant mortality in individuals with Barth syndrome (BTHS), a rare genetic disorder due to mutations in the tafazzin (TAZ) gene affecting mitochondrial structure and function. Investigations into the perturbed bioenergetics in the BTHS heart remain limited. Hence, our objective was to identify the potential alterations in myocardial energy metabolism and molecular underpinnings that may contribute to the early cardiomyopathy and heart failure development in BTHS. Cardiac function and myocardial energy metabolism were assessed via ultrasound echocardiography and isolated working heart perfusions, respectively, in a mouse model of BTHS (doxycycline-inducible Taz knockdown (TazKD) mice). In addition, we also performed mRNA/protein expression profiling for key regulators of energy metabolism in hearts from TazKD mice and their wild-type (WT) littermates. TazKD mice developed hypertrophic cardiomyopathy as evidenced by increased left ventricular anterior and posterior wall thickness, as well as increased cardiac myocyte cross sectional area, though no functional impairments were observed. Glucose oxidation rates were markedly reduced in isolated working hearts from TazKD mice compared to their WT littermates in the presence of insulin, which was associated with decreased pyruvate dehydrogenase activity. Conversely, myocardial fatty acid oxidation rates were elevated in TazKD mice, whereas no differences in glycolytic flux or ketone body oxidation rates were observed. Our findings demonstrate that myocardial glucose oxidation is impaired prior to the development of overt cardiac dysfunction in TazKD mice, and may thus represent a pharmacological target for mitigating the development of cardiomyopathy in BTHS.

Abstract 13320: Direct Cardiac Actions of Empagliflozin Improve Mitochondrial Oxidative Phosphorylation and Attenuate Pressure-overload Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Xuan Li ◽  
Jussara M do Carmo ◽  
Zhen Wang ◽  
Alexandre A da Sivla ◽  
Alan J Mouton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Molecular Docking ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Biogenesis ◽  
Glucose Transporters ◽  
Left Ventricular ◽  
Mitochondrial Morphology ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Docking Analysis ◽  
Molecular Docking Analysis

Introduction: The underlying mechanisms by which empagliflozin (EMPA) and other sodium glucose co-transporter 2 (SGLT2) inhibitors attenuate heart failure (HF) are still poorly understood. However, this protection does not appear to be fully explained by their antihyperglycemic or diuretic effects. Hypothesis: EMPA attenuates HF by direct effects on the heart to improve its metabolism and function. Methods: C57BL/6J mice (4-6 months) were subjected to transverse aortic constriction (TAC) or sham surgeries. Two weeks after TAC, EMPA (10 mg/kg/day) or vehicle was administered daily for 4 additional weeks. Cardiac function was assessed by echocardiography and cardiac substrate metabolism measured in isolated perfused hearts. Transmission electron microscopy was used to evaluate mitochondrial morphology and molecular docking analysis to predict potential cardiac targets of EMPA. Results: EMPA increased survival and attenuated adverse left ventricle remodeling and cardiac fibrosis after TAC. EMPA also attenuated left ventricular systolic dysfunction (ejection fraction 51.6 vs. 40.2% p<0.05; fraction shortening 28.8 vs 18.4% p<0.05). EMPA rescued impaired glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. Molecular docking analysis and isolated perfused heart experiments indicated that EMPA can directly bind glucose transporters in the heart to reduce glycolysis, and enhance AMP-activated protein kinase. EMPA treatment enhanced mitochondrial biogenesis, restored mitochondria cristae integrity, increased expression of endogenous antioxidants, and reduced cellular apoptosis caused by leakage of cytochrome C from mitochondria into the cytosol. These beneficial cardiac effects of EMPA occurred despite no alterations in fasting blood glucose, body weight, or daily urine volume. Conclusions. Our study demonstrated that EMPA may directly bind glucose transporters and reduce excessive glycolysis in failing hearts. EMPA enhanced mitochondrial biogenesis, improved mitochondrial oxidative phosphorylation, and reduced mitochondria-mediated apoptosis, thereby attenuating cardiac dysfunction and progression of HF.

scholarly journals Effect of Allopurinol on Myocardial Energy Metabolism in Chronic Heart Failure Rats After Myocardial Infarct

2016 ◽  
Vol 57 (6) ◽  
pp. 753-759 ◽  
Author(s):  
Zhenzhen Wang ◽  
Juan Ding ◽  
Xiang Luo ◽  
Siliang Zhang ◽  
Gang Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Chronic Heart Failure ◽  
Myocardial Infarct ◽  
Myocardial Energy Metabolism

scholarly journals Creatine deficiency and heart failure

2021 ◽  
Author(s):  
Annamaria Del Franco ◽  
Giuseppe Ambrosio ◽  
Laura Baroncelli ◽  
Tommaso Pizzorusso ◽  
Andrea Barison ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Adenosine Triphosphate ◽  
Creatine Supplementation ◽  
Energy Deficit ◽  
Clinical Value ◽  
Comprehensive Overview ◽  
Cardiac Energy Metabolism ◽  
Creatine Deficiency ◽  
Cardiac Energy

AbstractImpaired cardiac energy metabolism has been proposed as a mechanism common to different heart failure aetiologies. The energy-depletion hypothesis was pursued by several researchers, and is still a topic of considerable interest. Unlike most organs, in the heart, the creatine kinase system represents a major component of the metabolic machinery, as it functions as an energy shuttle between mitochondria and cytosol. In heart failure, the decrease in creatine level anticipates the reduction in adenosine triphosphate, and the degree of myocardial phosphocreatine/adenosine triphosphate ratio reduction correlates with disease severity, contractile dysfunction, and myocardial structural remodelling. However, it remains to be elucidated whether an impairment of phosphocreatine buffer activity contributes to the pathophysiology of heart failure and whether correcting this energy deficit might prove beneficial. The effects of creatine deficiency and the potential utility of creatine supplementation have been investigated in experimental and clinical models, showing controversial findings. The goal of this article is to provide a comprehensive overview on the role of creatine in cardiac energy metabolism, the assessment and clinical value of creatine deficiency in heart failure, and the possible options for the specific metabolic therapy.

scholarly journals Impact of circadian time of dosing on cardiac-autonomous effects of glucocorticoids

2021 ◽  
Author(s):  
Michelle Wintzinger ◽  
Manoj Panta ◽  
Karen Miz ◽  
Ashok D.P. Pragasam ◽  
Michelle Sargent ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Demand ◽  
Heart Function ◽  
Daily Intake ◽  
Metabolic Stress ◽  
Single Pulse ◽  
High Energy ◽  
Dark Phase ◽  
Light Phase ◽  
Circadian Time

Bioenergetic capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates cardiac bioenergetics through the primary receptor of these drugs, the glucocorticoid receptor (GR). While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism and heart function in dystrophic mice. However, the effects of glucocorticoid intermittence on heart failure beyond muscular dystrophy remain unknown. Here we investigated the extent to which circadian time of dosing regulates the cardiac-autonomous effects of the glucocorticoid prednisone in conditions of single pulse or chronic intermittent dosing. In WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted GR ablation, and depended on an intact activating clock complex, as shown by hearts from BMAL1-KO mice. Conjugating time-of-dosing with chronic intermittence, we found that once-weekly light-phase prednisone improved metabolism and function in heart after myocardial injury. Our study identifies cardiac-autonomous mechanisms through which circadian time and chronic intermittence reconvert glucocorticoid drugs to bioenergetic boosters for the heart.

Abstract 289: Relationship Between Myocardial Glycogen Concentrations and Amplitude Spectrum Area During Ventricular Fibrillation in a Rat Model of Cardiac Arrest and Resuscitation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Qiaohua Hu ◽  
Xiangshao Fang ◽  
Zhengfei Yang ◽  
Wanchun Tang
Keyword(s):  
Cardiac Arrest ◽  
Energy Metabolism ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Glycogen Content ◽  
Amplitude Spectrum ◽  
High Energy ◽  
Myocardial Energy Metabolism ◽  
Spectrum Area ◽  
The Relationship

Introduction: Myocardial high-energy phosphate (ATP) levels has been demonstrated correlating with amplitude spectrum area (AMSA) during ventricular fibrillation (VF) in previous experimental studies. In the present study, we investigated the relationship between AMSA and myocardial glycogen content (MGC),which can be used to reflect the status of myocardial energy metabolism indirectly during VF. Hypothesis: AMSA has a significantly correlation with MGC during VF in a rat model of cardiac arrest and resuscitation. Methods: Twenty male Sprague-Dawley rats weighing 350 to 450 g were utilized and randomized into two groups: VF and cardiopulmonary resuscitation (CPR) (VF/CPR group) or untreated VF (VF group). 5 mins of CPR was performed after 10 mins of untreated VF in VF/CPR animals. Amplitude spectrum area (AMSA) at VF 5, 10 and 15 mins were calculated from ECG signals. The rats’ hearts were quickly removed at the predetermined time of 15 min for determines the glycogen contents by the anthrone reagent method using a glycogen assay kit. Results: AMSA values significantly decreased during untreated VF in both VF and VF/CPR animals. However, much greater AMSA during CPR was achieved by the VF/CPR group in comparison with the VF group. There was a marked and negative relationship between AMSA at VF 15 min and MGC. (Figure). Conclusion: MGC was significantly and negatively correlated with AMSA during VF in this rat model of cardiac arrest and resuscitation. In clinical practice, we can use AMSA to reflect the state of myocardial energy metabolism indirectly. Figure The changes of AMSA and relationship between AMSA and glycogen content:(A) The change of AMSA between VF/CRP group and VF group;(B) The relationship between AMSA and glycogen content. AMSA, amplitude spectrum area; V, time of ventricular fibrillation; # p <0.05 vs. V4.

scholarly journals Clinical motivation for31P MRS studies on the myocardial energy metabolism of brain dead cats

2003 ◽  
Vol 17 (2-3) ◽  
pp. 503-510
Author(s):  
G. J. Brandon Bravo Bruinsma ◽  
C. J. A. Van Echteld
Keyword(s):  
Energy Metabolism ◽  
Brain Death ◽  
Hemodynamic Instability ◽  
High Energy ◽  
Exclusion Criterion ◽  
High Energy Phosphates ◽  
Myocardial Energy Metabolism ◽  
Brain Dead ◽  
The Brain ◽  
Death Group

Hemodynamic instability of the brain dead potential heart donor is an exclusion criterion for heart donation for transplantation. Based on the results of myocardial biopsies it has been reported that brain death-related catecholamine induced damage of the heart causes depletion of high-energy phosphates which could explain contractile dysfunction. Our group has shown in a series of31P MRS experiments in cats that neither the onset of brain death, nor the hemodynamic deterioration which follows, nor its treatment with high dosages of dopamine affect the heart energetically as expressed by PCr/ATP ratios. However, after cardioplegic arrest and explantation, an initial and prolonged lower ATP content and an anomalous higher PCr/ATP ratio in the brain death group was found when compared with controls during long-term unperfused cold storage of the hearts. During subsequent reperfusion of the hearts, ATP and PCr levels in the brain death group were lower than in controls but equal partial recovery of PCr/ATP ratios was observed in both groups. It was concluded that PCr/ATP ratios need to be interpreted with great caution. Secondly, brain death-related hemodynamic instability is not related to significant changes of myocardial energy metabolism. Thirdly, brain death does affect the myocardial energy metabolism but the impact became apparent only during hypothermic storage and subsequent reperfusion of the donor heart.

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