glycogen and Heart-Failure

Parenteral nutrition has been one of the major advances in clinical medicine in the 20th century. By maintaining or re-establishing optimal nutritional status, one can help to ensure an optimal response to appropriate medical or surgical management of the primary disease process. In order to plan an appropriate nutritional regimen, the health-care provider must be equipped to pursue the following thought processes: Understand the consequences of malnutrition. Identify the patient who may benefit from nutritional support. Assess the underlying clinical and metabolic setting. Assess the current nutritional status. Formulate a goal of nutritional intervention--a therapeutic plan. Determine the route and method of administration; the quantity and source of energy and nitrogen; and requirements for fluid, electrolytes, minerals, vitamins, and trace elements. Monitor the patient. Evaluate the efficacy and determine the duration of therapy.

Topics: Catheterization; Dietary Carbohydrates; Dietary Proteins; Energy Metabolism; Female; Glycogen; Heart Failure; Hepatic Encephalopathy; Humans; Intraoperative Period; Kidney Diseases; Male; Metabolic Diseases; Parenteral Nutrition, Total; Pregnancy; Starvation; Stress, Physiological; Triglycerides

Topics: Fatty Acids, Nonesterified; Glucose; Glucosyltransferases; Glycogen; Glycolysis; Heart Diseases; Heart Failure; Humans; Hydrogen-Ion Concentration; Hypoxia; Ketone Bodies; Lipid Metabolism; Myocarditis; Myocardium; Oxidative Phosphorylation; Phosphofructokinase-1; Pyruvates; Triglycerides

Topics: Bronchodilator Agents; Dipyridamole; Endoplasmic Reticulum; Glycogen; Heart; Heart Failure; Humans; Isoproterenol; Metaproterenol; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Phenethylamines; Resorcinols

Plasma levels of ammonia and hypoxanthine (HX) can be indices of purine nucleotide degradation. The present study determined if patients with heart failure (HF) have altered exercise plasma ammonia and HX levels relative to the peak work rate performed. Blood lactate, plasma ammonia, and plasma HX levels were measured in 59 patients with HF (New York Heart Association [NYHA] classes I:20, II:21, and III:18) and 21 controls at rest and after a maximal cardiopulmonary exercise test. The peak work rate (normal and NYHA I, II, and III, 163+/-11, 152+/-9, 94+/-5, and 69+/-5 W) and peak oxygen uptake ([VO2] 32.3+/-1.7, 25.1+/-0.9, 18.6+/-0.5, and 14.1+/-0.6 mL/min/kg) decreased as the NYHA functional class increased. The increment from rest to peak exercise (delta) for lactate ([(delta)lactate] 6.1+/-0.3, 4.8+/-0.4, 4.6+/-0.3, and 2.9+/-0.3 mmol/L), (delta)ammonia (132+/-14, 119+/-20, 94+/-13, and 32+/-6 microg/dL), and (delta)HX (33.5+/-3.4, 24.9+/-4.7, 20.6+/-3.0, and 9.9+/-1.2 micromol/L) was progressively smaller as HF worsened. The ratio for (delta)lactate to peak work rate (0.037+/-0.003, 0.032+/-0.004, 0.049+/-0.003, and 0.042+/-0.005) was higher in classes II to III HF, while the ratio for (delta)ammonia to peak work rate (0.81+/-0.14, 0.78+/-0.16, 0.99+/-0.11, and 0.47+/-0.11) was significantly lower in class III HF. In summary, patients with HF exhibited a smaller ammonia response with a higher lactate response to exercise when normalized with the peak work rate. These results suggest there may be an altered purine and glycogen metabolism during exercise in skeletal muscle in patients with HF.

Topics: Ammonia; Blood Pressure; Exercise; Exercise Test; Female; Glycogen; Heart Failure; Heart Rate; Humans; Hypoxanthine; Lactic Acid; Male; Middle Aged; Muscle, Skeletal; Purines; Respiratory Mechanics

The objective of the study was to investigate the impact of alteration of glycogen stores and metabolism on exercise performance in patients with heart failure.. In normal subjects, muscle glycogen depletion results in increased exertional fatigue and reduced endurance. Skeletal muscle biopsies have revealed reduced glycogen content in patients with congestive heart failure (CHF). Whether glycogen depletion contributes to reduced endurance and abnormal ventilation in these patients is unknown.. Bicycle exercise tests with measurement of respiratory gases were performed following dietary manipulations to induce glycogen depletion (60% protein, 40% fat) and slow glycogen utilization (60% carbohydrate, 30% fat, 10% protein) in 13 patients with CHF (left ventricular ejection fraction 22+/-6%; age 48+/-9 years) and 7 control subjects (age 45+/-5 years). Maximal exercise, exercise at 75% of peak workload until exhaustion and 1-min cycles of supramaximal exercise at 133% of peak were performed on three occasions over a two-week period.. Significant changes in resting respiratory quotients (RQs) in normal (Baseline: 0.78+/-0.03; Depleted: 0.69+/-0.05) and CHF subjects (Baseline: 0.84+/-0.05; Depleted: 0.72+/-0.05) were observed (both p<0.05). Peak Vo2 (oxygen consumption) in both groups was unchanged. The ventilatory response to exercise was analyzed by correlating CO2 production (V(CO2)) to minute ventilation (VE) in each test. The slopes of these correlations were not affected in either group. With glycogen depletion, exercise endurance was reduced from 17 to 6.1 min (57+/-19%) in normal subjects versus a reduction of 9.4 to 8.1 min (11+/-19%) in patients (p<0.05). With slowed glycogen use, CHF patients increased exercise endurance from 9.4 to 16.5 min (65%) versus 17 to 20.6 min (18%) in normal subjects (p<0.05).. Glycogen depletion minimally affects maximal exercise performance, endurance or ventilation in CHF patients, whereas slowed glycogen utilization markedly enhances exercise endurance. Therapeutic interventions that increase or slow use of glycogen stores may have clinical benefit.

Topics: Adult; Cardiomyopathy, Dilated; Coronary Disease; Diet; Exercise; Exercise Test; Female; Glycogen; Heart Failure; Humans; Male; Middle Aged; Muscle, Skeletal; Physical Endurance; Prospective Studies

By using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation of muscle metabolism in patients with chronic heart failure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a double-blind manner to receive either placebo (n = 11) or enalapril (n = 11) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril.

Topics: Adenosine Triphosphate; Aged; Aged, 80 and over; Biopsy; Double-Blind Method; Drug Therapy, Combination; Enalapril; Energy Metabolism; Exercise Test; Female; Furosemide; Glycogen; Heart Failure; Hemodynamics; Humans; Lactates; Lactic Acid; Male; Middle Aged; Muscles; Phosphocreatine; Survival Rate

Diabetic cardiomyopathy (DCM) is linked to disturbance in cardiac glucose handling and increased cardiac glycogen storage. This study tested the potential role of sacubitril/valsartan on the progression of DCM in high fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic rats compared to valsartan alone, including their effects on the cardiac glycophagy process.. Rats were fed on HFD for 6 weeks followed by single low-dose STZ (35 mg/kg). After confirming hyperglycemia, diabetic rats were continued on HFD and divided into three subgroups: Untreated-diabetic, Valsartan-treated diabetic and Sacubitril/valsartan-treated diabetic groups; in addition to a control group. Changes in ECG, blood glucose, serum insulin, lipid profile, and Homeostasis model of assessment of insulin resistance (HOMA-IR) were assessed and the degree of cardiac fibrosis was examined. Cardiac glycogen content and glycophagy process were evaluated.. Sacubitril/valsartan administration to diabetic rats resulted in improvement of metabolic changes more than valsartan alone. Also, sacubitril/valsartan effectively prevented diabetes-associated cardiac hypertrophy, QTc prolongation, and fibrosis. Finally, cardiac glycogen concentrations in diabetic rats were decreased by sacubitril/valsartan combination, coupled with significant induction of glycophagy process in the diabetic rats' heart.. Sacubitril/valsartan therapy provides a more favorable metabolic and cardioprotective response compared to valsartan alone in a rat model of DCM. These findings may be due to a direct cardioprotective impact of sacubitril/valsartan and secondary beneficial effects of improved hyperglycemia and dyslipidemia. In addition, these beneficial cardiac effects could be attributed to the induction of the glycophagy process and alleviating cardiac glycogen overload.

Topics: Aminobutyrates; Animals; Biphenyl Compounds; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Drug Combinations; Glycogen; Heart Failure; Hyperglycemia; Mice; Rats; Stroke Volume; Tetrazoles; Valsartan

Myocardial remodelling is important pathological basis of HF, mitochondrial oxidative stress is a promoter to myocardial hypertrophy, fibrosis and apoptosis. ECH is the major active component of a traditional Chinese medicine Cistanches Herba, plenty of studies indicate it possesses a strong antioxidant capacity in nerve cells and tumour, it inhibits mitochondrial oxidative stress, protects mitochondrial function, but the specific mechanism is unclear. SIRT1/FOXO3a/MnSOD is an important antioxidant axis, study finds that ECH binds covalently to SIRT1 as a ligand and up-regulates the expression of SIRT1 in brain cells. We hypothesizes that ECH may reverse myocardial remodelling and improve heart function of HF via regulating SIRT1/FOXO3a/MnSOD signalling axis and inhibit mitochondrial oxidative stress in cardiomyocytes. Here, we firstly induce cellular model of oxidative stress by ISO with AC-16 cells and pre-treat with ECH, the level of mitochondrial ROS, mtDNA oxidative injury, MMP, carbonylated protein, lipid peroxidation, intracellular ROS and apoptosis are detected, confirm the effect of ECH in mitochondrial oxidative stress and function in vitro. Then, we establish a HF rat model induced by ISO and pre-treat with ECH. Indexes of heart function, myocardial remodelling, mitochondrial oxidative stress and function, expression of SIRT1/FOXO3a/MnSOD signalling axis are measured, the data indicate that ECH improves heart function, inhibits myocardial hypertrophy, fibrosis and apoptosis, increases the expression of SIRT1/FOXO3a/MnSOD signalling axis, reduces the mitochondrial oxidative damages, protects mitochondrial function. We conclude that ECH reverses myocardial remodelling and improves cardiac function via up-regulating SIRT1/FOXO3a/MnSOD axis and inhibiting mitochondrial oxidative stress in HF rats.

Topics: Animals; Apoptosis; Cardiomegaly; Cell Line; Forkhead Box Protein O3; Glycogen; Glycosides; Heart Failure; Isoproterenol; Male; Mitochondria; Myocardium; Oxidative Stress; Rats, Sprague-Dawley; Sirtuin 1; Superoxide Dismutase; Up-Regulation; Vascular Endothelial Growth Factor A; Ventricular Remodeling

Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes, including enhanced insulin sensitivity. However, the function of myostatin in the heart is barely understood, although it is upregulated in the myocardium under several pathological conditions.. Here, we aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for cardiac function and cardiac metabolism in adult mice. To avoid potential counterregulatory mechanisms occurring in constitutive and germ-line-based myostatin mutants, we generated a mouse model that allows myostatin inactivation in adult cardiomyocytes.. Cardiac MRI revealed that genetic inactivation of myostatin signaling in the adult murine heart caused cardiac hypertrophy and heart failure, partially recapitulating effects of the age-dependent decline of the myostatin paralog growth and differentiation factor 11. We found that myostatin represses AMP-activated kinase activation in the heart via transforming growth factor-β-activated kinase 1, thereby preventing a metabolic switch toward glycolysis and glycogen accumulation. Furthermore, myostatin stimulated expression of regulator of G-protein signaling 2, a GTPase-activating protein that restricts Gaq and Gas signaling and thereby protects against cardiac failure. Inhibition of AMP-activated kinase in vivo rescued cardiac hypertrophy and prevented enhanced glycolytic flow and glycogen accumulation after inactivation of myostatin in cardiomyocytes.. Our results uncover an important role of myostatin in the heart for maintaining cardiac energy homeostasis and preventing cardiac hypertrophy.

Topics: AMP-Activated Protein Kinases; Animals; Cardiomyopathy, Hypertrophic, Familial; Cell Lineage; Energy Metabolism; Gene Expression Regulation; Glycogen; Glycolysis; Heart Failure; Homeostasis; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Myostatin; Recombinant Fusion Proteins; RGS Proteins; Signal Transduction

Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure.. Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion.. Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3±6.9% of initial value vs. 28.5±5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0±16.3% while in Control hearts 19.7±4.0%. LDH release in these hearts was also 3 fold lower compared to Control.. Consecutive Iso/Ade treatment of normal heart can be effective at clinically-relevant doses and this effect appears to be mediated by glycogen depletion and inhibition of MPTP. This intervention protects clinically relevant failing heart model making it a promising candidate for clinical use.

Topics: Adenosine; Animals; Glycogen; Heart Failure; Hemodynamics; In Vitro Techniques; Isoproterenol; Male; Myocardium; Rats; Rats, Wistar; Reperfusion Injury

Metabolism of contractile cardiomyocyte in experimental pulmonary stenosis complicated or not complicated by heart failure was studied by histochemical methods. In pulmonary stenosis not complicated by heart failure, intensification of glycolysis, more intense oxidation of free fatty acids and their metabolites, and acceleration of the citric acid cycle were found in the contractile cardiomyocytes. In pulmonary stenosis complicated by heart failure, glycogen content in the myocardium was sharply decreased. The histochemical enzyme profile of contractile cardiomyocytes is similar in pulmonary stenosis with and without heart failure. Comparative analysis of changes occurring in acute increase in afterload of the left or right ventricle suggested that in the latter case, metabolic abnormalities in the contractile cardiomyocytes are relatively unimportant in the pathogenesis of heart failure.

Topics: Animals; Citric Acid Cycle; Fatty Acids, Nonesterified; Glycogen; Glycolysis; Guinea Pigs; Heart Failure; Heart Ventricles; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Oxidation-Reduction; Pulmonary Valve Stenosis

The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Adaptation, Physiological; Animals; ATP Citrate (pro-S)-Lyase; Disease Models, Animal; Energy Metabolism; Female; Glycogen; Glycolysis; Heart Failure; Hindlimb; Hypertension; Muscle Contraction; Muscle, Skeletal; Physical Exertion; Rats; Rats, Inbred SHR; Rats, Inbred WF; RNA, Messenger; Running; Time Factors

Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury.. CrT-OE mice were selected for left ventricular (LV) creatine 20-100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury.. Elevation of myocardial creatine by 20-100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia.

Topics: Animals; Cell Line; Creatine; Disease Models, Animal; Energy Metabolism; Glycogen; Heart Failure; Magnetic Resonance Imaging, Cine; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardial Stunning; Myocardium; Necrosis; Oxidative Stress; Phosphocreatine; Time Factors; Up-Regulation; Ventricular Function, Left; Ventricular Remodeling

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficiency in glycogen-branching enzyme (GBE1) activity that results in the accumulation of amylopectin-like polysaccharide, which presumably leads to osmotic swelling and cell death. This disease is extremely heterogeneous in terms of tissue involvement, age of onset and clinical manifestation. The most severe fetal form presents as hydrops fetalis; however, its pathogenetic mechanisms are largely unknown. In this study, mice carrying a stop codon mutation (E609X) in the Gbe1 gene were generated using a gene-driven mutagenesis approach. Homozygous mutants (Gbe(-/-) mice) recapitulated the clinical features of hydrops fetalis and the embryonic lethality of the severe fetal form of GSD-IV. However, contrary to conventional expectations, little amylopectin accumulation and no cell degeneration were found in Gbe(-/-) embryonic tissues. Glycogen accumulation was reduced in developing hearts of Gbe(-/-)embryos, and abnormal cardiac development, including hypertrabeculation and noncompaction of the ventricular wall, was observed. Further, Gbe1 ablation led to poor ventricular function in late gestation and ultimately caused heart failure, fetal hydrops and embryonic lethality. We also found that the cell-cycle regulators cyclin D1 and c-Myc were highly expressed in cardiomyocytes and likely contributed to cardiomyocyte proliferation and trabeculation/compaction of the ventricular wall. Our results reveal that early molecular events associated with Gbe1 deficiency contribute to abnormal cardiac development and fetal hydrops in the fetal form of GSD-IV.

Topics: 1,4-alpha-Glucan Branching Enzyme; Amylopectin; Animals; Cell Cycle Proteins; Cell Proliferation; Codon, Terminator; Cyclin D1; Embryo Loss; Fluorescent Antibody Technique; Genes, myc; Glycogen; Glycogen Storage Disease Type IV; Heart; Heart Defects, Congenital; Heart Failure; Heart Rate; Hydrops Fetalis; Mice; Myocytes, Cardiac; Polymerase Chain Reaction; Sequence Analysis, DNA; Ventricular Function

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. The antihyperglycaemic drug MET (metformin) affects substrate metabolism, and its use might be associated with improved outcome in diabetic HF. The aim of the present study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Volume-overload HF was induced in male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized to placebo/MET (300 mg·kg(-1) of body weight·day(-1), 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6-12/group) in advanced HF stage (week 21). A separate cohort served for survival analysis (n=10-90/group). The ACF group had marked cardiac hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) and lung weight confirming decompensated HF, increased circulating NEFAs (non-esterified 'free' fatty acids), intra-abdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triacylglycerol (triglyceride) content and attenuated myocardial (14)C-glucose and (14)C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels (2.2±0.7 μg/ml). In conclusion, MET-induced enhancement of myocardial fatty acid oxidation had a neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Blood Glucose; Body Weight; Disease Models, Animal; Drug Evaluation, Preclinical; Glycogen; Heart Failure; Hemodynamics; Hypoglycemic Agents; Lipid Metabolism; Lung; Male; Metformin; Mitochondria, Heart; Myocardium; Organ Size; Protein Kinases; Rats; Rats, Wistar; Survival Analysis; Ultrasonography

Topics: Animals; Biological Transport; Genes; Glucose; Glucose Transporter Type 1; Glycogen; Heart Failure; Hypertrophy, Left Ventricular; Mice; Monosaccharide Transport Proteins; Myocardium

To investigate the metabolic response of skeletal muscle to exercise in patients with chronic heart failure and determine its relation to central haemodynamic variables.. University hospital in Sweden.. 16 patients in New York Heart Association class II-III and 10 healthy controls.. Skeletal muscle biopsies were obtained from the quadriceps muscle at rest and at submaximal and maximal exercise. Right sided heart catheterisation was performed in eight patients.. The patients had lower maximal oxygen consumption than the control group (13.2 (2.9) v 26.8 (4.4) ml/kg/min, P < 0.001). They had reduced activities of citrate synthetase (P < 0.05) and 3-hydroxyacyl-CoA dehydrogenase (P < 0.05) compared with the controls. At maximal exercise adenosine triphosphate (P < 0.05), creatine phosphate (P < 0.01), and glycogen (P < 0.01) were higher whereas glucose (P < 0.001) and lactate (P < 0.06) were lower in the patients than in the controls. Citrate synthetase correlated inversely with skeletal muscle lactate at submaximal exercise (r = -0.90, P < 0.003). No correlations between haemodynamic variables and skeletal muscle glycogen, glycolytic intermediates, and adenosine nucleotides during exercise were found.. Neither skeletal muscle energy compounds nor lactate accumulation were limiting factors for exercise capacity in patients with chronic heart failure. The decreased activity of oxidative enzymes may have contributed to the earlier onset of anaerobic metabolism, but haemodynamic variables seemed to be of lesser importance for skeletal muscle metabolism during exercise.

Topics: Adenosine Triphosphate; Aged; Cardiac Catheterization; Exercise; Exercise Test; Female; Glucose; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Heart Failure; Humans; Lactates; Lactic Acid; Male; Middle Aged; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine

To distinguish between the effects of reduced oxidative capacity and reduced metabolic efficiency on skeletal muscle bioenergetics during exercise in patients with congestive heart failure.. Patients were studied by 31P magnetic resonance spectroscopy during aerobic exercise and recovery, and results compared with controls.. In flexor digitorum superficialis muscle (26 patients) there was a 30% decrease in oxidative capacity compared with control (mean (SE) 36 (2) v 51 (4) mM/min) and also a 40% decrease in "effective muscle mass" (5 (1) v 9 (1) arbitrary units), probably at least partly the result of reduced metabolic efficiency. Both contribute to increased phosphocreatine depletion and intracellular acidosis during exercise. However, an increased concentration of ADP (an important mitochondrial regulator) during exercise permitted near-normal rates of oxidative ATP synthesis. Results were similar in gastrocnemius muscle (20 patients), with a 30% decrease in maximum oxidative capacity (29 (4) v 39 (3) mM/min) and a 65% decrease in effective muscle mass (5 (1) v 13 (2) arbitrary units). Exercise training improved maximum oxidative capacity in both muscles, and in gastrocnemius effective muscle mass also.. Skeletal muscle exercise abnormalities in patients with congestive heart failure results more from decreased metabolic efficiency than from the abnormalities in mitochondrial oxidation. Both decreased efficiency and defective mitochondrial oxidation result in an increased activation of glycogen phosphorylase, and may be improved by exercise training.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Energy Metabolism; Exercise; Glycogen; Heart Failure; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal

A 14-year-old boy with mild mental retardation, myopathy, and nonobstructive hypertrophic cardiomyopathy (HCM) with clinical and histopathologic features consistent with lysosomal glycogen storage disease with normal acid maltase is described. The case illustrates the aggressive nature of the cardiomyopathy of this syndrome. This condition is associated with malignant ventricular arrhythmias, relentlessly progressive ventricular dilatation, dysfunction, and sudden death. It is important to recognize this unusual and malignant form of HCM to precipitate low early diagnosis by muscle biopsy. Patients with this condition would be excellent candidates for life-saving heart transplant as the myopathy and mental retardation are mild and nonprogressive. The underlying biochemical defect and mode of inheritance of this syndrome are unclear. However, a significant proportion are genetically related and thus, relatives may benefit from family screening.

Topics: Adolescent; Cardiomyopathy, Hypertrophic; Glucan 1,4-alpha-Glucosidase; Glycogen; Heart Failure; Humans; Intellectual Disability; Lysosomal Storage Diseases; Male; Syndrome

We have assessed the deleterious effects of methyl methacrylate (MMA) on cardiac function and metabolism in the isolated heart-lung preparation and their protection by ulinastatin. Twenty-four male Wistar rats were prepared for the heart-lung model. They were randomly divided into 3 groups. In the MMA (M) and ulinastatin (U) groups, MMA 1000 micrograms.ml-1 was administered 7 minutes after the start of perfusion. At the end of the experimental period, the hearts were freeze-clamped and then myocardial high energy phosphates, lactate and glycogen were measured. Cardiac output decreased significantly in the M and U groups. Po2 of the perfusion blood in the M and U groups was significantly lower than that in the control (C) group. Myocardial ATP in the M and U groups was significantly lower than that in the C group. ADP and AMP in the M and U groups were higher than those in the C group. Although there was no significant difference in lactate levels among the 3 groups, glycogen in the U and C groups was significantly higher than that in the M group. MMA 1000 micrograms.ml-1 is much higher than the blood level (0.05-31.89 micrograms.ml-1) reported clinically in patients who had femoral prosthesis. Ulinastatin increased myocardial glycogen content which had been reduced by MMA. This may suggest that ulinastatin has a protective effect on heart damaged by MMA.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Animals; Bone Cements; Cardiac Output; Glycogen; Glycoproteins; Heart Failure; Hemodynamics; Humans; In Vitro Techniques; Male; Methylmethacrylate; Methylmethacrylates; Myocardium; Rats; Rats, Wistar

Rapid ventricular pacing (RVP) is used as an experimental model of congestive heart failure (CHF). The purpose of this study was to determine the energy status of the dog myocardium after the development of CHF via chronic RVP. The myocardium had a significantly lower (P < 0.05) energy charge (EC) during CHF (0.63 +/- 0.01) than in sham-operated controls (0.82 +/- 0.02). This was due to significant differences in concentrations in ATP (-48%), ADP (29%), and AMP (275%) in the RVP group. However, the total adenine nucleotide pool was not different between groups. Myocardial lactate concentration was also similar. Glycogen was significantly lower (P < 0.05) by 20% at peak CHF. The adenine nucleotides were similar among the different myocardial layers (endo-, mid-, and epicardium). The administration of enalapril (an inhibitor of angiotension-converting enzyme) to decrease vascular resistance had no effect on the myocardial energy status of CHF dogs. These findings suggest that the lower EC in CHF animals is not the result of subendocardial ischemia. Also, lower EC is not associated with endogenous glycogen depletion or increased lactate concentration. The energy status of the myocardium in RVP-induced CHF is unlike that seen in ischemia-induced heart failure. This suggests that CHF in RVP is not vascular in origin.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Cardiac Pacing, Artificial; Dogs; Enalapril; Energy Metabolism; Glycogen; Heart; Heart Failure; Lactates; Myocardium; Vascular Resistance; Ventricular Function

A case of 25-year-old woman with glycogen storage myopathy is reported here. She was hospitalized for acute heart failure after alcohol drinking. The electrocardiogram on admission showed marked ST elevation. Laboratory data showed elevated levels of serum myogenic enzymes but no rise in cardiomyogenic enzyme: CK 3862 IU/l CK-MB 35 IU/l, LDH 427 IU/l, GOT 203 IU/l. After several days, she recovered from acute heart failure and could walk without supporting. ST elevation in ECG and elevated myogenic enzymes were also normalized. The occurrence of acute myocardial infarction was ruled out because a coronary angiogram and 99 Tcm scintigram were normal. Physical examination revealed proximal muscular weakness and mental retardation (WAIS, total 72). Venous lactate response was normal after semi-ischemic forearm exercise. PAS staining of muscle specimen showed an excess deposit of glycogen. Ragged-red fibers were not seen on Gomori-trichrome stain. By electron microscopy, a large amount of glycogen particles were demonstrated in the subsarcolemma, but there were no abnormal mitochondrial changes. Biochemical analysis showed accumulation of glycogen in muscles: 28.7 mg/g muscle (normal 11.4 +/- 4.2 mg/g muscle). The activities of enzyme in the pathway of glycogen and glycogenosis (alpha-glucosidase, amylo-1,6-glucosidase, phosphorylase a, phosphorylase kinase, phosphofructokinase, etc.) were within normal limits. The spectrum of glycogen iodine complex was normal. Our case was different from any type of muscle glycogen storage disease previously reported. The etiology of an excess of glycogen deposit in muscles is unknown.

Topics: Acute Disease; Adult; alpha-Glucosidases; Female; Glycogen; Glycogen Storage Disease; Heart Failure; Humans; Muscles; Muscular Diseases

A male patient is reported with a mutation of acid alpha-glucosidase causing an altered Km toward natural substrates. Cardiac arrhythmia was found at 12 years of age, and he died of heart failure at 15 years. No skeletal muscle involvement was observed either clinically or histologically. Acid alpha-glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4-methylumbelliferyl alpha-D-glucoside. The hydrolysis of glycogen was markedly decreased (14% of the control mean), and the Km for maltose was increased 4-fold and for glycogen 5-fold. The biosynthesis and the posttranslational processing of the mutant enzyme appeared normal, but the total amount of the enzyme was lower than normal. This mutant enzyme comigrated with normal acid alpha-glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid alpha-glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycogenesis II are discussed.

Topics: Adolescent; alpha-Glucosidases; Arrhythmias, Cardiac; Cardiomyopathies; Fibroblasts; Glycogen; Heart Failure; Humans; Kinetics; Male; Muscles; Myocardium; Substrate Specificity

The endurance capacities of rats with myocardial infarctions (MI) and of rats having undergone sham operations (SHAM) were tested during a submaximal exercise regimen that consisted of swimming to exhaustion. During this test, a decrement in the endurance capacity of the MI rat was demonstrated as the SHAM rat swam 25% longer than the MI rat (65 +/- 4 vs. 52 +/- 4 min). Glycogen concentrations were measured in the liver and the white gastrocnemius, plantaris, and soleus muscles of SHAM and MI rats that were randomly divided into four subgroups, which consisted of resting control, swim to exhaustion, swim to exhaustion + 24 h recovery, and swim to exhaustion + 24 h recovery + a second swim to exhaustion. The results demonstrated that the glycogen concentrations found in the liver, white gastrocnemius, plantaris, and soleus muscles of the SHAM and MI rats belonging to the resting control groups were similar. After swimming to exhaustion the glycogen concentrations in these tissues were significantly reduced compared with those found in the resting control groups of rats, and after 24 h of recovery the glycogen concentrations in these tissues were again similar to those found in the resting control groups of rats. Since the magnitude of the glycogen depletion in the liver and the white gastrocnemius, plantaris, and soleus muscles was similar in the SHAM and MI rats and because the SHAM rats consistently swam for longer periods of time in each of the experimental groups, it would be logical to assume that the rates of glycogen utilization for the various tissues may have been greater in the MI rat during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Chronic Disease; Fatigue; Female; Glycogen; Heart Failure; Liver Glycogen; Muscles; Myocardial Infarction; Physical Endurance; Physical Exertion; Random Allocation; Rats; Rats, Inbred Strains

Topics: Echocardiography; Female; Furosemide; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Heart Failure; Humans; Infant; Infant, Newborn; Muscles; Myocardium; Prognosis; Twins, Monozygotic

Electron-microscopical examination of myocardial biopsy material obtained from a 58-year-old man revealed giant mitochondria having a length of 30 micron. Such giant mitochondria (also called megamitochondria) evolve by fusion of the membranes of numerous large individual organelles. Initially they are polymorphous and of diverse shapes, but later they are seen to be arranged among and parallel with the filaments of the myocardial fibres, where they present a smooth, cigar-like appearance. Deposits of glycogen in the giant mitochondria result from the accidental inclusion of glycogen granules during fusion. The abundance of cristae, which often form dense stacks in the megamitochondria, is evidence for the genuine synthesis of new cristal material. The aetiological and exact pathogenetic mechanisms of the evolution of giant mitochondria in the myocardium, as also their function, remain unclear. Particularly large specimens are obviously inefficient and disturbing to the cell. They are degraded by autophagy.

Topics: Autophagy; Biopsy; Glycogen; Heart Failure; Humans; Male; Microscopy, Electron; Middle Aged; Mitochondria, Heart; Myocardium

In exsudate cells separated from serous body cavities of 29 tumour patients and 30 patients with inflammatory and congestive effusion in cardiac failure or liver cirrhosis respectively the activities of acid and alkaline phosphatase were determined. In addition to sudanophilia the cell content of glycogen and that of ribonucleinic acid were evaluated. By means of cytochemical findings it could be found that an increase of unspecific esterase, acid phosphatase and ribonucleic acid in atypical cells points to a malignous ethiology of the exudate.

Topics: Acid Phosphatase; Alkaline Phosphatase; Ascitic Fluid; Esterases; Exudates and Transudates; Glycogen; Heart Failure; Histocytochemistry; Hodgkin Disease; Humans; Leukemia; Liver Cirrhosis; Lymphoma, Large B-Cell, Diffuse; Neoplasms; Peritonitis; Pleural Effusion; Pleurisy; RNA

Skeletal muscle metabolite concentrations were determined in 19 patients in either cardiogenic shock or severe left ventricular failure by obtaining a needle biopsy specimen of lateral thigh muscle. Evidence of anaerobic skeletal muscle metabolism was found in both patient groups with the greatest lactate accumulation and most severe high-energy phosphate depletion present in the patients in cardiogenic shock. The skeletal muscle lactate accumulation was most pronounced in the patients that died. Blood lactate values did not absolutely predict skeletal muscle lactate concentrations in those patients in whom skeletal muscle lactate concentrations were the highest. The patients in cardiogenic shock and severe left ventricular failure who survived demonstrated a reduction in skeletal muscle lactate levels and a restoration of high-energy phosphates over several days which correlated with clinical and hemodynamic improvement.

Topics: Adenosine Triphosphate; Adult; Aged; Biopsy, Needle; Carbon Dioxide; Female; Glucose; Glucosephosphates; Glycogen; Heart Failure; Humans; Hydrogen-Ion Concentration; Lactates; Male; Middle Aged; Muscles; Oxygen; Partial Pressure; Phosphocreatine; Shock, Cardiogenic

Topics: Animals; Glycogen; Golgi Apparatus; Heart Failure; Histocytochemistry; Hyperthyroidism; Lipids; Lysosomes; Male; Mitochondria, Muscle; Myocardium; Myofibrils; Oxygen Consumption; Papillary Muscles; Rats; Sarcoplasmic Reticulum; Thyroid Function Tests

Topics: Adult; Animals; Cardiomegaly; Cell Nucleus; Dogs; Endocardial Fibroelastosis; Glycogen; Heart Arrest; Heart Diseases; Heart Failure; Humans; Hypoxia; Male; Middle Aged; Mitochondria, Muscle; Myocardium; Tetralogy of Fallot; Wolff-Parkinson-White Syndrome

Topics: Animals; Aortic Valve Stenosis; Capillaries; Cardiomegaly; Cats; Cineangiography; Collagen; Coronary Vessels; Disease Models, Animal; Dogs; Electrocardiography; Glycogen; Heart Conduction System; Heart Failure; Histological Techniques; Microscopy, Electron; Myocardium; Myofibrils; Organ Size; Organoids; Pulmonary Valve Stenosis; Rabbits

Topics: Adenine Nucleotides; Animals; Cardiomegaly; Collagen; Disease Models, Animal; DNA; Glycogen; Heart Failure; Mitochondria, Muscle; Muscle Proteins; Myocardium; Myofibrils; Organ Size; Rabbits; RNA; Sarcoplasmic Reticulum; Time Factors

Topics: Adolescent; Adult; Biopsy; Cardiomyopathies; Endoplasmic Reticulum; Female; Glycogen; Heart Failure; Heart Ventricles; Histocytochemistry; Humans; Lipids; Male; Microscopy, Electron; Middle Aged; Mitochondria; Myocardium; Myofibrils; Organoids

Topics: Adaptation, Physiological; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Aortic Valve Insufficiency; Biopsy; Cardiomegaly; Glycogen; Heart Failure; Heart Ventricles; Lactates; Muscle Proteins; Myocardium; Phosphocreatine; Rabbits

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Disease Models, Animal; Glycogen; Glycolysis; Heart; Heart Failure; Heart Rate; Hypoxia; In Vitro Techniques; Lactates; Male; Methods; Mitochondria, Muscle; Myocardium; Phosphorylases; Rats; Time Factors

Topics: Aged; Aging; Blood Pressure; Cardiac Output; Cardiomyopathies; Cell Nucleus; Climate; Digitalis Glycosides; Electrocardiography; Glycogen; Heart Failure; Heart Rate; Humans; Insecta; Mitochondria, Muscle; Physical Exertion; Time Factors; Vectorcardiography; Virus Diseases

Topics: Cardiomegaly; Electrocardiography; Electromyography; Female; Glucosidases; Glycogen; Glycogen Storage Disease; Heart; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Infant; Liver; Lymphocytes; Muscles; Myocardium; Radiography

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adenylyl Cyclases; Adolescent; Adult; Aged; Animals; Cardiac Surgical Procedures; Child; Chromatography; Epinephrine; Female; Glucose-6-Phosphatase; Glutamates; Glycogen; Guinea Pigs; Heart Failure; Heart Ventricles; Humans; Lactates; Malates; Male; Middle Aged; Norepinephrine; Papillary Muscles; Pyruvates; Radionuclide Imaging

Topics: Adrenergic beta-Antagonists; Animals; Arrhythmias, Cardiac; Cardiovascular System; Digestive System; Glycogen; Heart Failure; Hemodynamics; Humans; Hypertension; Lipid Metabolism; Lung; Myocardial Infarction; Spleen; Sympatholytics

Topics: Biopsy; Cardiomyopathies; Child; Cytoplasm; Electrocardiography; Female; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Golgi Apparatus; Heart Failure; Hepatomegaly; Humans; Infant; Infant, Newborn; Liver; Male; Microscopy, Electron; Mitochondria, Liver; Mitochondria, Muscle; Muscles; Myocardium; Myofibrils; Respiratory Distress Syndrome, Newborn

Topics: Adult; Beer; Biopsy; Cardiomyopathies; Edema; Electrocardiography; Glycogen; Heart Failure; Humans; Leg; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardium

Topics: Adaptation, Physiological; Altitude; Animals; Aortic Coarctation; Cerebral Cortex; Disease Models, Animal; Glycogen; Heart; Heart Failure; Hypoxia; Methods; Muscle Contraction; Myocardium; Phosphocreatine; Protein Biosynthesis; Rats; RNA

Topics: Coronary Disease; Diagnosis, Differential; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycolysis; Heart Failure; Histocytochemistry; Humans; Hypokalemia; Lactates; Myocardium; Potassium; Rheumatic Heart Disease

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Glucose; Glycogen; Glycolysis; Heart Failure; Hexosephosphates; Lactates; Myocardium; Nitrobenzenes; Perfusion; Phosphates; Phosphocreatine; Pyruvates; Rabbits

Topics: Cardiomegaly; Death, Sudden; Female; Glycogen; Heart Failure; Heart Neoplasms; Humans; Infant; Infant, Newborn; Male; Rhabdomyoma; Rhabdomyosarcoma

Topics: Acetylcholine; Animals; Aorta, Abdominal; Aortic Diseases; Electrocardiography; Glycogen; Heart; Heart Failure; Myocardium; Potassium; Rabbits; Radiography; Sodium; Tachycardia; Vagotomy

Topics: Acetylcholine; Adrenal Cortex Hormones; Adrenal Glands; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Aorta, Abdominal; Aortic Diseases; Diphtheria Toxin; Electrocardiography; Glycogen; Heart; Heart Failure; Myocardium; Potassium; Rabbits; Radiography; Sodium

Topics: Acetylcholine; Animals; Aorta; Bradycardia; Cholinesterase Inhibitors; Diphtheria Toxin; Glycogen; Heart; Heart Failure; Potassium; Rabbits; Reserpine

Topics: Adrenal Cortex Hormones; Adrenalectomy; Carbohydrate Metabolism; Glycogen; Heart Failure; Homeostasis; Lactates; Myocardium; Physiology; Pyruvates; Rabbits; Research

Topics: Animals; Glucose; Glycogen; Heart Failure; Myocardium; Physical Exertion; Rats

Topics: Biopsy; Chlorides; Collagen; Electrolytes; Glycogen; Heart Failure; Histocytochemistry; Humans; Muscle Proteins; Muscles; Potassium; Sodium; Water-Electrolyte Balance

Topics: Acetylcholine; Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Blood Chemical Analysis; Cardiomegaly; Cholinesterases; Constriction; Electrocardiography; Electrolytes; Follow-Up Studies; Glycogen; Heart Failure; Histocytochemistry; Rabbits; Research; Water; Water-Electrolyte Balance

Topics: Animals; Carbohydrate Metabolism; Cardiomegaly; Glycogen; Heart Failure; Lactates; Metabolism; Myocardium; Pyruvates; Pyruvic Acid; Rabbits; Research

Topics: Child; Diabetes Mellitus; Edema; Edetic Acid; Glycogen; Heart Failure; Humans; Infant

Topics: Ascorbic Acid; Glycogen; Heart; Heart Failure; Myocardium; Sulfhydryl Compounds

Topics: Glycogen; Heart Failure; Humans; Liver; Muscles