glycogen and Cardiomegaly

5'-AMP-activated protein kinase (AMPK) is a pivotal regulator of endogenous defensive molecules in various pathological processes. The AMPK signaling regulates a variety of intracellular intermedial molecules involved in biological reactions, including glycogen metabolism, protein synthesis, and cardiac fibrosis, in response to hypertrophic stimuli. Studies have revealed that the activation of AMPK performs a protective role in cardiovascular diseases, whereas its function in cardiac hypertrophy and cardiomyopathy remains elusive and poorly understood. In view of the current evidence of AMPK, we introduce the biological information of AMPK and cardiac hypertrophy as well as some upstream activators of AMPK. Next, we discuss two important types of cardiomyopathy involving AMPK, RKAG2 cardiomyopathy, and hypertrophic cardiomyopathy. Eventually, therapeutic research, genetic screening, conflicts, obstacles, challenges, and potential directions are also highlighted in this review, aimed at providing a comprehensive understanding of AMPK for readers.

Topics: Adolescent; AMP-Activated Protein Kinases; Animals; Cardiomegaly; Cardiomyopathies; Child, Preschool; Glycogen; Heart; Humans; Hypoglycemic Agents; Male; Metformin; Molecular Targeted Therapy; Myocardium; Signal Transduction

Topics: Adaptation, Physiological; Adenosine Triphosphatases; Animals; Blood Pressure; Blood Volume; Cardiac Output; Cardiomegaly; Cardiovascular Physiological Phenomena; Coronary Vessels; Energy Metabolism; Glycogen; Heart; Heart Rate; Hemoglobins; Humans; Lung; Male; Myocardium; Oxygen Consumption; Physical Conditioning, Animal; Physical Education and Training; Rats; Sports Medicine

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; DNA; Fatty Acids, Nonesterified; Glycogen; Glycolysis; Humans; Hypoxia; Mitochondria, Muscle; Muscle Proteins; Myocardial Infarction; Myocardium; Oxidation-Reduction; Oxygen Consumption; Rats; Regeneration

Topics: Adrenal Insufficiency; Animals; Biomechanical Phenomena; Blood Pressure; Calcium; Cardiac Glycosides; Cardiomegaly; Citric Acid Cycle; Cyclic AMP; Fatty Acids; Glycogen; Glycolysis; Heart; Hemodynamics; Homeostasis; Humans; Hypertrophy; In Vitro Techniques; Intercellular Junctions; Mitochondria, Muscle; Muscle Contraction; Myocardium; NAD; Phosphofructokinase-1; RNA; Ventricular Function

Topics: Animals; Birth Weight; Blood Glucose; Carbohydrate Metabolism; Cardiomegaly; Female; Fetus; Glucose; Glycogen; Haplorhini; Humans; Hydrocortisone; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Lipids; Liver; Polycythemia; Pre-Eclampsia; Pregnancy; Prognosis; Rabbits; Sex Factors; Time Factors

Topics: Animals; Animals, Newborn; Blood Pressure; Cardiac Output; Cardiomegaly; Death, Sudden; Electrocardiography; Female; Fetal Heart; Glycogen; Heart; Heart Conduction System; Heart Rate; Heart Ventricles; Hemodynamics; Hindlimb; Humans; Infant; Infant, Newborn; Myocardium; Organ Size; Oxygen Consumption; Pregnancy; Regional Blood Flow; Sheep; Sleep; Swine; Vascular Resistance; Ventricular Fibrillation

During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.

Topics: Animals; Animals, Newborn; Cardiomegaly; Diet, High-Fat; Enzyme Activation; Feeding Behavior; Female; Gene Deletion; Glucose Intolerance; Glycogen; Glycogen Synthase; Glycogen Synthase Kinase 3; Insulin Resistance; Lipid Metabolism; MAP Kinase Signaling System; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 12; Mitogen-Activated Protein Kinase 13; Myocardium; Myocytes, Cardiac; Organ Specificity; Phosphorylation

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

Topics: Animals; Cardiomegaly; Crosses, Genetic; Enzyme-Linked Immunosorbent Assay; Fever; Gene Expression Profiling; Glycogen; Heart Rate; Hypothyroidism; Lipolysis; Liver; Male; Mental Retardation, X-Linked; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Phenotype; Telemetry; Thermogenesis; Thermography; Thyroid Hormones; Time Factors; Triiodothyronine

PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many phenotypes of PRKAG2 cardiac syndrome including cellular enlargement, electrophysiological irregularities and glycogen storage. In addition, we found that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC-cardiomyocytes would be a very useful platform for understanding the pathogenesis of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome.

Topics: Adult; AMP-Activated Protein Kinases; Base Sequence; Calcium; Cardiomegaly; Cell Differentiation; Electrophysiological Phenomena; Glycogen; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Male; Mitochondria; Models, Biological; Mutation; Myocardial Contraction; Myocytes, Cardiac; Oxidation-Reduction; Phenotype; Reproducibility of Results; Syndrome

AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.

Topics: AMP-Activated Protein Kinases; Animals; Blood Glucose; Blood Pressure; Cardiomegaly; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Glycogen; Heart; Heterocyclic Compounds; Holoprosencephaly; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Jaw Abnormalities; Metformin; Mice; Mice, Obese; Muscle, Skeletal; Rats; Stroke Volume

5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades of investigation, the biological roles of AMPK and its potential as a drug target remain incompletely understood, largely because of a lack of optimized pharmacological tools. We developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.

Topics: AMP-Activated Protein Kinases; Animals; Benzimidazoles; Blood Glucose; Cardiomegaly; Fasting; Glucose; Glycogen; Homeostasis; Hypoglycemia; Imidazoles; Insulin; Macaca mulatta; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Pyridines

Cardiac failure has been widely associated with an increase in glucose utilization. The aim of our study was to identify factors that mechanistically bridge this link between hyperglycemia and heart failure. Here, we screened the Hybrid Mouse Diversity Panel (HMDP) for substrate-specific cardiomyocyte candidates based on heart transcriptional profile and circulating nutrients. Next, we utilized an in vitro model of rat cardiomyocytes to demonstrate that the gene expression changes were in direct response to substrate abundance. After overlaying candidates of interest with a separate HMDP study evaluating isoproterenol-induced heart failure, we chose to focus on the gene

Topics: Animals; Cardiomegaly; Cardiotonic Agents; Cell Size; Cells, Cultured; Gene Expression Profiling; Gene Knockdown Techniques; Glucose; Glycogen; Glycolysis; In Vitro Techniques; Isoproterenol; Mice; Myocytes, Cardiac; Rats; RNA, Small Interfering; Substrate Specificity; Transcription Factors

Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF.. To analyze the histological changes associated with isolated MS and compare between changes in AF and SR.. This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF.. On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm.. In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria.

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Biopsy; Cardiomegaly; Female; Fibrosis; Glycogen; Heart Atria; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Stenosis; Multivariate Analysis; Odds Ratio; Prospective Studies; Rheumatic Heart Disease; Risk Factors; Young Adult

Exercise-induced cardiac hypertrophy has been recently identified to be regulated in a sex-specific manner. In parallel, women exhibit enhanced exercise-mediated lipolysis compared with men, which might be linked to cardiac responses. The aim of the present study was to assess if previously reported sex-dependent differences in the cardiac hypertrophic response during exercise are associated with differences in cardiac energy substrate availability/utilization. Female and male C57BL/6J mice were challenged with active treadmill running for 1.5 h/day (0.25 m/s) over 4 wk. Mice underwent cardiac and metabolic phenotyping including echocardiography, small-animal PET, peri-exercise indirect calorimetry, and analysis of adipose tissue (AT) lipolysis and cardiac gene expression. Female mice exhibited increased cardiac hypertrophic responses to exercise compared with male mice, measured by echocardiography [percent increase in left ventricular mass (LVM): female: 22.2 ± 0.8%, male: 9.0 ± 0.2%; P < 0.05]. This was associated with increased plasma free fatty acid (FFA) levels and augmented AT lipolysis in female mice after training, whereas FFA levels from male mice decreased. The respiratory quotient during exercise was significantly lower in female mice indicative for preferential utilization of fatty acids. In parallel, myocardial glucose uptake was reduced in female mice after exercise, analyzed by PET {injection dose (ID)/LVM [%ID/g]: 36.8 ± 3.5 female sedentary vs. 28.3 ± 4.3 female training; P < 0.05}, whereas cardiac glucose uptake was unaltered after exercise in male counterparts. Cardiac genes involved in fatty acid uptake/oxidation in females were increased compared with male mice. Collectively, our data demonstrate that sex differences in exercise-induced cardiac hypertrophy are associated with changes in cardiac substrate availability and utilization.

Topics: Adipose Tissue; Animals; Blotting, Western; Calorimetry; Cardiomegaly; Echocardiography; Energy Metabolism; Female; Fluorodeoxyglucose F18; Glucose; Glycogen; Hypertrophy, Left Ventricular; Lactic Acid; Lipolysis; Male; Mice; Mice, Inbred C57BL; Myocardium; Physical Conditioning, Animal; Positron-Emission Tomography; Radiopharmaceuticals; RNA; Running; Sex Characteristics

Adrenomedullin (ADM) has been recognized as a multipotent multifunctional peptide. To explore the pathophysiological roles of ADM in insulin resistance (IR), we studied the changes in ADM mRNA level in the myocardium and vessels and the effect of ADM supplementation on rats with IR induced by fructose feeding. Rats were fed 4% fructose in drinking water for 8 weeks, and ADM was administered subcutaneously in pure water through an Alzet Mini-osmotic Pump at 300 ng/kg/h for the last 4 weeks. Compared with controls, rats with IR showed increased levels of fasting blood sugar and serum insulin, by 95% and 67%, respectively (all P<0.01), and glycogen synthesis and glucose transport activity of the soleus decreased by 54% and 55% (all P<0.01). mRNA level and content of brain natriuretic peptide (BNP) in myocardial were all increased significantly. Fructose-fed rats showed increased immunoreactive-ADM content in plasma by 110% and in myocardia by 55% and increased mRNA level in myocardia and vessels (all P<0.01). ADM administration ameliorated the induced IR and myocardial hypertrophy. The glycogen synthesis and glucose transport activity of the soleus muscle increased by 41% (P<0.01) and 32% (P<0.05). ADM therapy attenuated myocardial and soleus lipid peroxidation injury and enhanced the antioxidant ability. Our results showed upregulation of endogenous ADM during fructose-induced IR and the protective effect of ADM on fructose-induced IR and concomitant cardiovascular hypertrophy probably by its antioxidant effect, which suggests that ADM could be an endogenous protective factor in IR.

Topics: Adrenomedullin; Animals; Blood Glucose; Cardiomegaly; Cardiotonic Agents; Fructose; Glycogen; Infusion Pumps; Infusions, Subcutaneous; Insulin; Insulin Resistance; Lipid Peroxidation; Male; Malondialdehyde; Muscle, Skeletal; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We investigated cardiac hypertrophy elicited by rosiglitazone treatment at the level of protein synthesis/degradation, mTOR, MAPK and AMPK signalling pathways, cardiac function and aspects of carbohydrate/lipid metabolism. Hearts of rats treated or not with rosiglitazone (15 mg/kg day) for 21 days were evaluated for gene expression, protein synthesis, proteasome and calpain activities, signalling pathways, and function by echocardiography. Rosiglitazone induced eccentric heart hypertrophy associated with increased expression of ANP, BNP, collagen I and III and fibronectin, reduced heart rate and increased stroke volume. Rosiglitazone robustly increased heart glycogen content ( approximately 400%), an effect associated with increases in glycogenin and UDPG-PPL mRNA levels and glucose uptake, and a reduction in glycogen phosphorylase expression and activity. Cardiac triglyceride content, lipoprotein lipase activity and mRNA levels of enzymes involved in fatty acid oxidation were also reduced by the agonist. Rosiglitazone-induced cardiac hypertrophy was associated with an increase in myofibrillar protein content and turnover (increased synthesis and an enhancement of calpain-mediated myofibrillar degradation). In contrast, 26S beta5 chymotryptic proteasome activity and mRNA levels of 20S beta2 and beta5 and 19S RPN 2 proteasome subunits along with the ubiquitin ligases atrogin and CHIP were all reduced by rosiglitazone. These morphological and biochemical changes were associated with marked activation of the key growth-promoting mTOR signalling pathway, whose pharmacological inhibition with rapamycin completely blocked cardiac hypertrophy induced by rosiglitazone. The study demonstrates that both arms of protein balance are involved in rosiglitazone-induced cardiac hypertrophy, and establishes the mTOR pathway as a novel important mediator therein.

Topics: Animals; Atrial Natriuretic Factor; Blotting, Western; Body Weight; Cardiomegaly; Eating; Echocardiography; Glucosyltransferases; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Glycoproteins; Hemodynamics; Hypoglycemic Agents; Lipoprotein Lipase; Male; Myofibrils; Natriuretic Peptide, Brain; Proteasome Endopeptidase Complex; Protein Kinases; Rats; Rats, Sprague-Dawley; Rosiglitazone; Thiazolidinediones; TOR Serine-Threonine Kinases; UTP-Glucose-1-Phosphate Uridylyltransferase

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm(-/-)). Here, we show that Pfkm(-/-) mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm(-/-) mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm(-/-) mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm(-/-) mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies.

Topics: Animals; Cardiomegaly; Disease Models, Animal; Erythrocytes; Female; Glycogen; Glycogen Storage Disease Type VII; Hematologic Diseases; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Phosphofructokinase-1

Fatty acids (FAs) are acquired from free FA associated with albumin and lipoprotein triglyceride that is hydrolyzed by lipoprotein lipase (LpL). Hypertrophied hearts shift their substrate usage pattern to more glucose and less FA. However, FAs may still be an important source of energy in hypertrophied hearts. The aim of this study was to examine the importance of LpL-derived FAs in hypertensive hypertrophied hearts. We followed cardiac function and metabolic changes during 2 wk of angiotensin II (ANG II)-induced hypertension in control and heart-specific lipoprotein lipase knockout (hLpL0) mice. Glucose metabolism was increased in ANG II-treated control (control/ANG II) hearts, raising it to the same level as hLpL0 hearts. FA uptake-related genes, CD36 and FATP1, were reduced in control/ANG II hearts to levels found in hLpL0 hearts. ANG II did not alter these metabolic genes in hLpL0 mice. LpL activity was preserved, and mitochondrial FA oxidation-related genes were not altered in control/ANG II hearts. In control/ANG II hearts, triglyceride stores were consumed and reached the same levels as in hLpL0/ANG II hearts. Intracellular ATP content was reduced only in hLpL0/ANG II hearts. Both ANG II and deoxycorticosterone acetate-salt induced hypertension caused heart failure only in hLpL0 mice. Our data suggest that LpL activity is required for normal cardiac metabolic compensation to hypertensive stress.

Topics: Adenosine Triphosphate; Angiotensin II; Animals; Blood Pressure; Cardiomegaly; Desoxycorticosterone; Fatty Acids; Glucose; Glycogen; Hypertension; Lipid Metabolism; Lipids; Lipoprotein Lipase; Mice; Mice, Knockout; Myocardium; Oxidation-Reduction; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Triglycerides

Although mutations in the gamma-subunit of AMP-activated protein kinase (AMPK) can result in excessive glycogen accumulation and cardiac hypertrophy, the mechanisms by which this occurs have not been well defined. Because >65% of cardiac AMPK activity is associated with the gamma1-subunit of AMPK, we investigated the effects of expression of an AMPK-activating gamma1-subunit mutant (gamma1 R70Q) on regulatory pathways controlling glycogen accumulation and cardiac hypertrophy in neonatal rat cardiac myocytes. Whereas expression of gamma1 R70Q displayed the expected increase in palmitate oxidation rates, rates of glycolysis were significantly depressed. In addition, glycogen synthase activity was increased in cardiac myocytes expressing gamma1 R70Q, due to both increased expression and decreased phosphorylation of glycogen synthase. The inhibition of glycolysis and increased glycogen synthase activity were correlated with elevated glycogen levels in gamma1 R70Q-expressing myocytes. In association with the reduced phosphorylation of glycogen synthase, glycogen synthase kinase (GSK)-3beta protein and mRNA levels were profoundly decreased in the gamma1 R70Q-expressing myocytes. Consistent with GSK-3beta negatively regulating hypertrophy via inhibition of nuclear factor of activated T cells (NFAT), the dramatic downregulation of GSK-3beta was associated with increased nuclear activity of NFAT. Together, these data provide important new information about the mechanisms by which a mutation in the gamma-subunit of AMPK causes altered AMPK signaling and identify multiple pathways involved in regulating both cardiac myocyte metabolism and growth that may contribute to the development of the gamma mutant-associated cardiomyopathy.

Topics: Active Transport, Cell Nucleus; AMP-Activated Protein Kinases; Animals; Animals, Newborn; Cardiomegaly; Cell Size; Cells, Cultured; Glucose; Glycogen; Glycogen Synthase; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Glycolysis; Hypertrophy; Multienzyme Complexes; Mutation; Myocytes, Cardiac; NFATC Transcription Factors; Oxidation-Reduction; Palmitic Acid; Phosphorylation; Protein Serine-Threonine Kinases; Rats; RNA, Messenger; Signal Transduction; Transduction, Genetic

Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function. We evaluated 24-hour ambulatory electrocardiograms (ECGs) at baseline and during ERT in patients with infantile Pompe disease.. Thirty-two ambulatory ECGs were evaluated for 12 patients with infantile Pompe disease from 2003 to 2005. Patients had a median age of 7.4 months (2.9-37.8 months) at initiation of ERT. Ambulatory ECGs were obtained at determined intervals and analyzed.. Significant ectopy was present in 2 of 12 patients. Patient 1 had 211 and 229 premature ventricular contractions (0.2% of heart beats) at baseline and at 11.5 weeks of ERT, respectively. Patient 2 had 10,445 premature ventricular contractions (6.7% of heart beats) at 11 weeks of therapy.. Infantile Pompe disease may have preexisting ectopy; it may also develop during the course of ERT. Therefore, routinely monitoring patients using 24-hour ambulatory ECGs is useful. Periods of highest risk may be early in the course of ERT when there is a substantial decrease in left ventricular mass and an initial decrease in ejection fraction.

Topics: alpha-Glucosidases; Cardiomegaly; Child, Preschool; Electrocardiography, Ambulatory; Female; Glycogen; Glycogen Storage Disease Type II; Heart Conduction System; Humans; Infant; Male; Recombinant Proteins; Ventricular Premature Complexes

It has been observed that opposite changes in cardiac workload result in similar changes in cardiac gene expression. In the current study, the hypothesis that altered gene expression in vivo results in altered substrate fluxes in vitro was tested. Hearts were perfused for 60 minutes with Krebs-Henseleit buffer containing glucose (5 mmol/L) and oleate (0.4 mmol/L). At 30 minutes, either insulin (1 mU/mL) or epinephrine (1 micromol/L) was added. Hearts weighed 35% less after unloading and 25% more after aortic banding. Contractile function in vitro was decreased in transplanted and unchanged in banded hearts. Epinephrine, but not insulin, increased cardiac power. Basal glucose oxidation was initially decreased and then increased by aortic banding. The stimulatory effects of insulin or epinephrine on glucose oxidation were reduced or abolished by unloading, and transiently reduced by banding. Oleate oxidation correlated with cardiac power both before and after stimulation with epinephrine, whereas glucose oxidation correlated only after stimulation. Malonyl-coenzyme A levels did not correlate with rates of fatty acid oxidation. Pyruvate dehydrogenase was not affected by banding or unloading. It was concluded that atrophy and hypertrophy both decrease insulin responsiveness and shift myocardial substrate preference to glucose, consistent with a shift to a fetal pattern of energy consumption; and that the isoform-specific changes that develop in vivo do not change the regulation of key metabolic enzymes when assayed in vitro.

Topics: Animals; Atrophy; Body Weight; Cardiomegaly; Enzyme Activation; Epinephrine; Fatty Acids; Glucose; Glycogen; Heart; Heart Transplantation; In Vitro Techniques; Insulin; Insulin Resistance; Male; Malonyl Coenzyme A; Myocardial Contraction; Myocardium; Oleic Acid; Organ Size; Oxidation-Reduction; Perfusion; Pyruvate Dehydrogenase Complex; Rats; Rats, Inbred WF

We determined the effect of insulin on the fate of glucose and contractile function in isolated working hypertrophied hearts from rats with an aortic constriction (n = 27) and control hearts from sham-operated rats (n = 27). Insulin increased glycolysis and glycogen in control and hypertrophied hearts. The change in glycogen was brought about by increased glycogen synthesis and decreased glycogenolysis in both groups. However, the magnitude of change in glycolysis, glycogen synthesis, and glycogenolysis caused by insulin was lower in hypertrophied hearts than in control hearts. Insulin also increased glucose oxidation and contractile function in control hearts but not in hypertrophied hearts. Protein content of glucose transporters, protein kinase B, and phosphatidylinositol 3-kinase was not different between the two groups. Thus hypertrophied hearts are less responsive to the metabolic and functional effects of insulin. The reduced responsiveness involves multiple aspects of glucose metabolism, including glycolysis, glucose oxidation, and glycogen metabolism. The absence of changes in content of key regulatory molecules indicates that other sites, pathways, or factors regulating glucose utilization are responsible for these findings.

Topics: Animals; Cardiomegaly; Glucose; Glycogen; Glycolysis; Hemodynamics; Immunoblotting; In Vitro Techniques; Insulin; Male; Monosaccharide Transport Proteins; Organ Size; Oxidation-Reduction; Perfusion; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley

We sought to determine whether improving coupling between glucose oxidation and glycolysis by stimulating glucose oxidation during reperfusion enhances postischemic recovery of hypertrophied hearts.. Low rates of glucose oxidation and high glycolytic rates are associated with greater postischemic dysfunction of hypertrophied as compared with nonhypertrophied hearts.. Heart function, glycolysis and glucose oxidation were measured in isolated working control and hypertrophied rat hearts for 30 min before 20 min of global, no-flow ischemia and during 60 min of reperfusion. Selected control and hypertrophied hearts received 1.0 mmol/liter dichloroacetate (DCA), an activator of pyruvate dehydrogenase, at the time of reperfusion to stimulate glucose oxidation.. In the absence of DCA, glycolysis was higher and glucose oxidation and recovery of function were lower in hypertrophied hearts than in control hearts during reperfusion. Dichloroacetate stimulated glucose oxidation during reperfusion approximately twofold in both groups, while significantly reducing glycolysis in hypertrophied hearts. It also improved function of both hypertrophied and control hearts. In the presence of DCA, recovery of function of hypertrophied hearts was comparable to or better than that of untreated control hearts.. Dichloroacetate, given at the time of reperfusion, normalizes postischemic function of hypertrophied rat hearts and improves coupling between glucose oxidation and glycolysis by increasing glucose oxidation and decreasing glycolysis. These findings support the hypothesis that low glucose oxidation rates and high glycolytic rates contribute to the exaggerated postischemic dysfunction of hypertrophied hearts.

Topics: Animals; Cardiomegaly; Dichloroacetic Acid; Disease Models, Animal; Glucose; Glycogen; Glycolysis; In Vitro Techniques; Male; Myocardial Reperfusion Injury; Myocardium; Oxidation-Reduction; Pyruvate Dehydrogenase Complex; Rats; Rats, Sprague-Dawley; Ventricular Function

Biotechnology research is developing into genomic analyses that involve the simultaneous monitoring of thousands of genes. The development of various bioinformatics resources that provide efficient access to information is necessary. We have used single-pass sequencing of randomly selected cDNA clones to generate expressed sequence tags (ESTs). These ESTs data has been widely used to study gene expression in a variety of heart libraries [1, 21]. Data annotation on our recent finding allows us to construct the profiles of genes in the energy metabolizing pathways (glycolysis and glycogen metabolism) that are expressed in heart cDNA libraries. In silico studies of genes of energy metabolism yields data that are consistent with results derived from conventional metabolic experiments. The change in gene profiles describing the metabolism of diseased hearts is also presented here.

Topics: Cardiomegaly; Cardiomyopathies; Computational Biology; Energy Metabolism; Expressed Sequence Tags; Gene Expression Regulation; Gene Library; Glucose; Glycogen; Glycolysis; Heart; Humans; Pyruvic Acid

We undertook this study to determine if the metabolism of exogenous glucose and glycogen in hypertrophied hearts differed from that in normal hearts during severe ischemia. Thus, rates of glycolysis (3H2O production) and oxidation (14CO2 production) from exogenous glucose and glycogen were measured in isolated working control (n = 13) and hypertrophied (n = 12) hearts from sham-operated and aortic-banded rats during 40 min of severe low-flow ischemia. Hearts, in which glycogen was prelabelled with [5-3H]- or [14C]-glucose, were paced and perfused with Krebs-Henseleit solution containing 1.2 mM palmitate, 5.5 mM [5-3H]- or [14C]-glucose (different from the isotope used to label glycogen), 0.5 mM lactate and 100 microU/ml insulin during ischemia. Rates of glycolysis from exogenous glucose (3301 +/- 122 v 2467 +/- 167 nmol/min/g dry wt, mean +/- S.E.M., P < 0.05) and glucose from glycogen (808 +/- 27 v 725 +/- 21 nmol/min/g dry wt, P < 0.05) were accelerated in hypertrophied hearts compared to control hearts. However, rates of oxidation of exogenous glucose and glucose from glycogen were not significantly different between the two groups. As observed in normoxic non-ischemic hearts, glucose from glycogen was preferentially oxidized compared to exogenous glucose. Additionally, rates of glycogen synthesis (167 +/- 7 v 140 +/- 9 nmol/min/g dry wt, P < 0.05) were increased in hypertrophied hearts compared to control hearts during severe low-flow ischemia indicating that glycogen turnover (i.e. simultaneous synthesis and degradation) was accelerated in the hypertrophied heart. Thus, we demonstrate that glucose utilization and glycogen turnover are accelerated in the hypertrophied heart during severe low-flow ischemia as compared to the normal heart.

Topics: Animals; Body Weight; Cardiomegaly; Glucose; Glycogen; Male; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Time Factors

Glycogen storage disease type II (GSDII; Pompe disease), caused by inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder affecting heart and skeletal muscles. A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa mRNA and have a virtually complete acid alpha-glucosidase deficiency. Glycogen-containing lysosomes are detected soon after birth in liver, heart and skeletal muscle cells. By 13 weeks of age, large focal deposits of glycogen have formed. Vacuolar spaces stain positive for acid phosphatase as a sign of lysosomal pathology. Both male and female knockout mice are fertile and can be intercrossed to produce progeny. The first born knockout mice are at present 9 months old. Overt clinical symptoms are still absent, but the heart is typically enlarged and the electrocardiogram is abnormal. The mouse model will help greatly to understand the pathogenic mechanism of GSDII and is a valuable instrument to explore the efficacy of different therapeutic interventions.

Topics: alpha-Glucosidases; Animals; Cardiomegaly; Disease Models, Animal; Female; Glycogen; Glycogen Storage Disease Type II; Male; Mice; Mice, Knockout

Rates of glycolysis from exogenous glucose are accelerated in hypertrophied hearts. In this study, we determined whether alterations in the metabolism of glycogen, an endogenous storage form of glucose, also occur in hypertrophied hearts.. Rates of glycolysis ([3H]H2O production) and oxidation ([14C]CO2 production) from exogenous glucose and glycogen were measured in isolated working hearts from control and aortic-banded rats. Hearts in which glycogen was prelabeled with [5-(3)H]- or [U-(14)C]glucose were perfused with buffer containing 11 mmol/L [5-(3)H]- or [U-(14)C]glucose (different from the isotope used to prelabel glycogen), 0.4 mmol/L palmitate, 0.5 mmol/L lactate, and 100 microU/mL insulin. Rates of glycolysis from exogenous glucose were greater (3471+/-114 versus 2665+/-194 nmol glucose x min(-1) x g dry wt(-1), P<.05, n=4 to 6, mean+/-SEM) and rates of exogenous glucose oxidation (445+/-36 versus 619+/-16 nmol glucose x min(-1) x g dry wt(-1), P<.05, n=4 to 6) were lower in hypertrophied hearts than in control hearts. Rates of glycolysis and oxidation from glycogen were not different between hypertrophied and control hearts. A greater proportion of glycogen was oxidized (80% to 100%) than the proportion of exogenous glucose oxidized (13% to 24%) in both groups. Additionally, 10.5+/-1.4 and 12.3+/-1.0 micromol/g dry wt of glycogen was synthesized in hypertrophied and control hearts, respectively, indicating that simultaneous synthesis and degradation (ie, glycogen turnover) occurred in both groups.. Thus, aerobic myocardial glycogen metabolism in the hypertrophied heart is similar to that observed in the normal heart even though exogenous glucose metabolism is altered in the hypertrophied heart.

Topics: Animals; Cardiomegaly; Glucose; Glycogen; Male; Oxidation-Reduction; Rats; Rats, Sprague-Dawley

Although hypertrophied hearts have increased rates of glycolysis under aerobic conditions, it is controversial as to whether glucose metabolism during ischemia is altered in the hypertrophied heart. Because endogenous glycogen stores are a key source of glucose during ischemia, we developed a protocol to label the glycogen pool in hearts with either [3H]glucose or [14C]glucose, allowing for direct measurement of both glycogen and exogenous glucose metabolism during ischemia. Cardiac hypertrophy was produced in rats by banding the abdominal aorta for an 8-week period. Isolated hearts from aortic-banded and sham-operated rats were initially perfused under substrate-free conditions to decrease glycogen content to 40% of the initial pool size. Resynthesis and radiolabeling of the glycogen pool with [3H]glucose or [14C]glucose were accomplished in working hearts by perfusion for a 60-minute period with 11 mmol/L [3H]glucose or [14C]glucose, 0.5 mmol/L lactate, 1.2 mmol/L palmitate, and 100 mumol/mL insulin. Although glycolytic rates during the aerobic perfusion were significantly greater in hypertrophied hearts compared with control hearts, glycolytic rates from exogenous glucose were not different during low-flow ischemia. The contribution of glucose from glycogen was also not different in hypertrophied hearts compared with control hearts during ischemia (1314 +/- 665 versus 776 +/- 310 nmol.min-1.g dry wt-1, respectively). Glucose oxidation rates decreased during ischemia but were not different between the two groups. However, in both hypertrophied and control hearts, the ratio of glucose oxidation to glycolysis was greater for glucose originating from glycogen than from exogenous glucose. Our data demonstrate that glycogen is a significant source of glucose during low-flow ischemia, but the data do not differ between hypertrophied and control hearts.

Topics: Animals; Cardiomegaly; Coronary Circulation; Glucose; Glycogen; Glycolysis; Heart; Male; Myocardial Ischemia; Myocardium; Oxidation-Reduction; Rats; Rats, Sprague-Dawley

Studies of the effect of sex on the metabolic state of rats with chronic hypertension and concomitant myocardial hypertrophy were conducted. Female and male spontaneously hypertensive rats (SHRs) with early myocardial hypertrophy (5.5 mo old) were used. Serum fatty acids, liver glycogen, and myocardial glycogen were measured at baseline and after the rats were deprived of food for 24 h. The metabolic effects of progressive myocardial hypertrophy in females were assessed in additional groups of female SHRs (5.5 or 12 mo old) under the following conditions: control, food deprived, or food deprived and refed with equienergetic lipid-rich (38.9% of total energy) or carbohydrate-rich (76.5% of total energy) diets. Despite no differences in serum fatty acids, females had significantly higher baseline myocardial glycogen and liver glycogen concentrations than males. In response to food deprivation, females continued to have significantly higher myocardial glycogen and fatty acid concentrations than males, whereas there were no sex differences in liver glycogen, which was depleted in both males and females. Older hypertensive females had higher baseline fatty acid concentrations and lower liver glycogen concentrations than younger females, whereas there were no differences in myocardial glycogen. Food deprivation doubled fatty acid concentrations, depleted liver glycogen, and increased myocardial glycogen in both age groups. In both age groups, fatty acid concentrations and liver glycogen did not return to baseline values after food deprivation and refeeding. In both age groups, fatty acid concentrations increased further after the lipid-rich diet whereas liver glycogen concentrations returned to approximately 50% of baseline values after the carbohydrate-rich diet. Refeeding with either diet did not significantly increase myocardial glycogen further. Thus, the metabolic response to dietary manipulation was influenced by both sex and, in females, progressive pathology.

Topics: Aging; Animals; Cardiomegaly; Diet; Fatty Acids; Female; Food Deprivation; Glycogen; Hypertension; Liver; Male; Rats; Rats, Inbred SHR; Sex Characteristics

CI-959 is an antiallergic/antiinflammatory agent currently in development. In rats, daily bolus intravenous administration of CI-959 at doses > or = 10 mg/kg was associated with development of cardiac hypertrophy. There was no morphologic or biochemical evidence of myocyte injury, and cardiac hypertrophy rapidly reversed after treatment was discontinued. Cardiac hypertrophy was not evident when CI-959 was given orally or by continuous intravenous infusion with ALZA osmotic pumps. Maximum plasma drug concentrations (Cmax) were significantly higher when CI-959 was given by bolus intravenous injection, suggesting that cardiac effects were dependent on high Cmax concentrations. When neonatal rat cardiomyocytes were exposed to CI-959 in vitro, there was no evidence of myocyte enlargement or increased protein content. Cardiac hypertrophy was prevented by pretreatment with nonselective beta- and beta 1-selective adrenoceptor blockers as well as with central sympatholytics. beta 2- and alpha-adrenoceptor blockers were ineffective in preventing cardiac hypertrophy. Bolus intravenous CI-959 administration resulted in prolonged hypotension and associated increase in plasma catecholamine levels, with apparent inhibition of reflex tachycardia. We conclude that CI-959-associated cardiac hypertrophy in rats was not a direct drug effect but instead was probably mediated by endogenous catecholaminergic stimulation of cardiac beta 1-adrenoceptors.

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Cardiomegaly; Catecholamines; Cells, Cultured; Creatine Kinase; Disease Models, Animal; Glycogen; Heart; Heart Rate; Infusion Pumps, Implantable; Infusions, Intravenous; L-Lactate Dehydrogenase; Microscopy, Electron; Myocardium; Rats; Rats, Sprague-Dawley; Rats, Wistar; Tetrazoles; Thiophenes

The effect of calcium activation on energy production was investigated in isolated perfused hearts from rats treated with triiodothyronine (T3) during 15 days (0.2 mg/kg/day) and in hearts of rats allowed to recover after T3-treatment during 15 days. Changes in phosphorylated compound concentrations were followed in the isolated hearts perfused with a glucose-pyruvate medium by 31P-NMR spectroscopy, when the external calcium concentration was increased from 0.5-1, 1.5 and 2 mM. As expected, T3-treatment resulted in the hypertrophy of the heart (50% increase in HW/BW) that was nearly reversible 15 days after discontinuation of the treatment. When compared to controls, creatine, phosphocreatine (PCr) and glycogen contents were lower (58, 24 and 17% decrease respectively) in the hypertrophied hearts and higher (10, 14 and 18% respectively) after regression of hypertrophy. Intracellular pH, ATP, inorganic phosphate concentrations and the phosphorylation potential were not altered under T3-treatment and after regression of hypertrophy, while calculated free ADP concentration was lower in hypertrophied hearts (control: 40 +/- 2 microM, T3-treatment: 21 +/- 1 microM, regression: 37 +/- 1 microM). Increasing the calcium concentration induced a similar increase in left ventricular developed pressure in the three groups of hearts, with inorganic phosphate concentration increasing with cardiac work. The PCr concentration slightly decreased while the ATP concentration did not change. In spite of different initial PCr concentrations, the evolutions of PCr and Pi concentrations for each stepwise increase in external calcium were similar in the three groups. It is concluded that, in spite of the well-known decrease in efficiency induced by the drug, the mechanisms of PCr (ATP) production remain able to respond to an acute moderate increase in energy demand provoked by a physiological stimulus. This adaptation also persists after the treatment when the energy metabolism balance is apparently improved.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Calcium; Cardiomegaly; Creatine; Energy Metabolism; Female; Glycogen; Heart; Hyperthyroidism; Magnetic Resonance Spectroscopy; Myocardial Contraction; Myocardium; Organ Size; Phosphates; Phosphocreatine; Rats; Rats, Sprague-Dawley; Triiodothyronine; Ventricular Pressure

The purpose of this study was to determine whether metabolites produced by glycolysis during ischemia significantly contribute to myocardial injury of hypertrophied hearts. The accumulation of glycolytic metabolites during ischemia was reduced by means of glycogen reduction or by treatment with the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) before ischemia. Hearts from aortic-banded (Band) and sham-operated (Sham) rats (8 wk postop) were isolated, perfused with Krebs buffer, and had a left ventricular (LV) balloon to measure developed pressure. A 15-min perfusion with hypoxic buffer (glycogen reduction, GR) or a 10-min perfusion with 10 mM 2-DG (glycolytic inhibition) was followed by 25 min global, normothermic, no-flow ischemia and 30 min normoxic reperfusion. Heart weights were greater in Band than Sham [2.76 +/- 0.06 vs. 1.5 +/- 0.04 (mean +/- SE) g; P < 0.001]. GR and 2-DG each resulted in reduced ATP levels measured at the beginning of ischemia in both Band and Sham groups compared with untreated groups, but there were no differences among groups after 25 min of ischemia. Myocardial lactate levels at the end of ischemia were significantly reduced in both Band and Sham hearts with GR or 2-DG compared with untreated controls. Recovery of LV function after ischemia and reperfusion was significantly improved in Band after GR (206% increase) and after 2-DG treatment (126% increase) compared with their respective untreated controls. Diastolic dysfunction during reperfusion was ameliorated in Band by preischemic GR but not by 2-DG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiomegaly; Deoxyglucose; Diastole; Glycogen; Glycolysis; Male; Myocardial Ischemia; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

Recirculating, retrograde heart perfusion according to the Langendorff method was used in an attempt to further elucidate the cardiotoxicity of methyl-2-tetradecylglycidate (McNeil 3716, MTG) and the eccentric hypertrophy elicited by the compound. In subchronic experiments female rats were exposed to MTG 2 x 10 mg/kg and 2 x 25 mg/kg per day for 4 weeks. At various times hearts were perfused ex vivo for up to 2 hr with either 5 mmolar glucose or 0.5 mmolar palmitate as substrate. Substrate uptake (glucose or palmitate) and enzyme release (LDH-lactic dehydrogenase or CPK-creatine-phosphate kinase) were assessed during perfusion. Biochemical analysis (ATP, ADP, AMP, c-AMP, CP, creatine, pyruvate, lactate, glucose-6-phosphate, glycogen, phospholipids, triglycerides and non-esterified fatty acids) were done in hearts before (drug effect) and after perfusion (stress of perfusion). Besides changes in energy metabolism and high-energy phosphate production, as observed in previous experiments (Bachmann et al. 1984) massive changes were seen in energy reserves in heart tissue (ATP, CP, glycogen, phospholipids and triglycerides). As expected, MTG led to significant increases also in non-esterified fatty acids content in hearts.

Topics: Adenine Nucleotides; Animals; Cardiomegaly; Creatine Kinase; Energy Metabolism; Epoxy Compounds; Fatty Acids, Nonesterified; Female; Glucose; Glycogen; Hypoglycemic Agents; L-Lactate Dehydrogenase; Lipid Metabolism; Myocardium; Palmitic Acids; Perfusion; Phosphocreatine; Propionates; Rats; Triglycerides

In order to study the initial development of myocardial ultrastructural changes owing to right atrium volume overload, myocytes have been studied in specimens taken from the right atrial wall and auricle of four children aged 1 to 6 years with ostium secundum atrial septal defect undergoing cardiac surgery. The younger patients (1 to 4-year-old children) we observed did not show diffuse and significant myocardial ultrastructural damages. The most significant myocardial changes were observed in the 2 older patients (six years old) as we found subcellular signs of myocardial hypertrophy such as an increased number of mitochondria, increased glycogen inclusions, areas of new sarcomerogenesis and nuclei lobulated and variably shaped. Focal degenerative changes, such as rupture of mitochondrial cristae and intercellular fibrosis were also noted. These changes may be considered as the initial features of myocardial hypertrophy because they were not as severe and diffuse as those usually seen in a marked functional failure.

Topics: Cardiomegaly; Child; Child, Preschool; Female; Fibrosis; Glycogen; Heart Atria; Heart Septal Defects, Atrial; Humans; Infant; Male; Mitochondria, Heart

The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury.

Topics: Adenosine Triphosphate; Animals; Aorta; Cardiomegaly; Constriction; Coronary Disease; Glycogen; Heart Ventricles; Hypoxia; Lactates; Lactic Acid; Male; Microscopy, Electron; Myocardial Contraction; Myocardium; Phosphocreatine; Pressure; Rats; Rats, Inbred Strains

The effect of different training regimes (three programmes of both swimming and running exercise) on the heart hypertrophy index and some biochemical indices was evaluated and compared individually with the sensitivity of the corresponding heart to ischaemia in order to elucidate the significance of training intensity and observed changes in the development of heart ischaemic injury. The sensitivity of the heart to ischaemia, evaluated by the rate of development of ischaemic contracture 48 h after completing the exercise programme, increased in parallel with an increase in the heart hypertrophy index. Experiments with different swimming programmes showed that the extent of cardiac hypertrophy increased together with an increase in the duration of everyday swimming bouts. Hypertrophied hearts from trained rats were characterized by greater mobilization of glycogen and increased incorporation of 32P into ATP when investigated 10 min after isoprenaline administration. During total ischaemia the development of ischaemic contracture was accelerated in catecholamine-stimulated trained hearts due to more rapid hydrolysis of ATP compared with that in the hearts from sedentary animals. It is suggested that the observed difference between hearts from sedentary and trained animals is, at least partially, connected with the higher sensitivity of myofibrils to Ca2+ in trained hearts.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Cardiomegaly; Coronary Disease; Glycogen; Heart; Isoproterenol; Male; Myocardial Contraction; Myocardium; Physical Conditioning, Animal; Rats; Rats, Inbred Strains; Running; Swimming

Abdominal aorta constriction was performed in 10-week-old Lewis rats (Aoband). Ten weeks later the hearts were isolated and attached to a non-recirculating perfusion apparatus. The hearts could eject against a diastolic aortic pressure of either 60 or 100 mmHg. The functional recovery was compared with that of hearts of sham-operated (Sham) rats. After 45 min of global ischemia, Sham hearts regained cardiac output up to 75% and 70% of the pre-ischemic levels at 60 and 100 mmHg, respectively. At 60 mmHg Aoband hearts showed a minor recovery of ejection function. However, at 100 mmHg the recovery of Aoband hearts was completely comparable with that of Sham hearts. At 60 mmHg but not at 100 mmHg, the pre-ischemic and post-ischemic coronary flow was lower in Aoband than in Sham hearts (P less than or equal to 0.05). During the initial reperfusion phase Sham hearts, perfused at 60 mmHg, released more degradation products of adenine nucleotides and lactate dehydrogenase (LDH) than Aoband hearts (P less than or equal to 0.05), while the Aoband hearts lost more degradation products and LDH than the Sham hearts later during the reperfusion phase (P less than or equal to 0.05). In the groups perfused at 60 mmHg, higher tissue levels of ATP were found in Sham than in Aoband hearts at the end of the reperfusion period (P less than or equal to 0.05). However, at 100 mmHg comparable levels were found in the Sham and Aoband hearts. It is concluded that the height of the coronary perfusion pressure is of critical importance for the post-ischemic functional recovery of the compensated hypertrophied heart. At sufficiently high perfusion pressure levels, the functional and biochemical recovery of the hypertrophied heart is at least as good as in the non-hypertrophied heart. However, in the hypertrophied heart a coronary perfusion pressure which is too low leads to relative underperfusion during the initial reperfusion period which is associated with severely depressed cardiac performance and delayed wash-out of metabolites and intracellular enzymes.

Topics: Adenine Nucleotides; Animals; Cardiomegaly; Coronary Circulation; Coronary Disease; Creatine Kinase; Glycogen; Hemodynamics; L-Lactate Dehydrogenase; Male; Myocardium; Rats; Rats, Inbred Lew

The ability to resist transient ischemia was studied in isolated hearts of 18 months old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Both types of hearts showed optimal performance during the preischemic period when perfused at a diastolic perfusion pressure of 8.0 (WKY) and 13.3 (SHR) kPa. Hemodynamic recovery of WKY hearts during reperfusion at 8.0 kPa, following 45 min global ischemia, was satisfactory. coronary perfusion completely normalized, contractility (dPlv/dtmax) was slightly depressed and cardiac output returned, on the average, to 40% of the preischemic values. In contrast, hemodynamic function of SHR hearts reperfused at 13.3 kPa was greatly depressed, as evidenced by almost complete abolition of cardiac output, severe reduction of dPlv/dtmax and persistent underperfusion of the endocardial layers. In addition, the postischemic release of lactate dehydrogenase was retarded and enhanced. The release patterns of degradation products of adenine nucleotides showed a shift to the endstage products xanthine and uric acid. The enhanced vulnerability of the hypertrophied heart to ischemia was even more expressed when the SHR hearts were reperfused at 8.0 kPa. Postischemic function was characterized by electrical instability, loss of contractility and cardiac output, and noreflow in the endocardial layers. Persistent accumulation of lactate and degradation products of adenine nucleotides in the postischemic hearts are in line with the lack of reperfusion. The present results indicate that a detailed mechanistic explanation for the reduced ability to withstand ischemia of SHR cannot be based on differences in ATP content or an altered anaerobic glycolitic activity prior and during ischemia. It is suggested that a defect on the circulatory level, probably caused by enhanced reactivity of the coronary vessels towards ischemia-elicited factors, is responsible for the higher vulnerability of hypertrophied heart to an ischemia insult.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Cardiac Output; Cardiomegaly; Coronary Circulation; Coronary Disease; Glycogen; L-Lactate Dehydrogenase; Myocardial Contraction; Myocardial Reperfusion; Phosphates; Phosphocreatine; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Glucose-insulin-potassium (GIK) given during myocardial ischemia or anoxemia results in improved myocardial function and augments energy reserves of myocardial glycogen (MG). Because many patients with heart disease also have myocardial hypertrophy, our purpose was to examine whether similar elevations in MG can occur in hypertrophic hearts with GIK administration and to study the effect of hypovolemic shock on those MG levels. Mongrel dogs (n = 5) with myocardial hypertrophy underwent serial myocardial biopsies of the left (LV) and right (RV) ventricles, and blood samples were followed by GIK infusion (14.5 ml/kg/hr) for 2 hr. after which the dogs were subjected to 2 hr of hypovolemic shock (mean arterial pressure = 40 mmHg). It was found that after GIK infusion MG was consistently elevated in both RV (.43 +/- .02 to .60 +/- .04 g%) and LV (.63 +/- .07 to .71 +/- .01 g%) and FFA declined (.20 +/- .05 to .05-.01 mEq/liter). The MG responded to hypovolemia by further significant elevations (RV 1.16 +/- .33; LV .82 +/- .17), as did FFA (.38 +/- .21). These results indicate that hypertrophic hearts can indeed respond to GIK infusion by increasing MG in both the RV and LV, as do normal hearts. These hearts then submitted to hypovolemic shock showed a further elevation of MG. The elevated insulin levels post-GIK resulted in suppression of FFA. Thus GIK administration may have a sparing effect on energy stores of the heart during hypovolemic shock, which could have clinical implications in the treatment of patients with hypertrophic myocardia.

Topics: Animals; Blood Glucose; Cardiomegaly; Dogs; Fatty Acids, Nonesterified; Female; Glucose; Glycogen; Heart Ventricles; Insulin; Male; Potassium; Shock

Glycogen storage disease type II Pompe (GSD II) is a lysosomal storage disease caused by an inherited deficiency of acid alpha-glucosidase. In addition to the classical infantile form of GSD II, several clinical variants are known. We describe an infant with the classical course of the disease. Our patient differs from the classical variant by the lack of cardiomegalia and the high residual activity of acid alpha-glucosidase in cultivated skin fibroblasts and muscle tissue. In the present case, however, glycogen storing lysosomes were found in peripheral lymphocytes and skeletal muscle cells. This finding underlines the particular value of ultrastructural investigation in the diagnosis of GSD II.

Topics: alpha-Glucosidases; Biopsy; Cardiomegaly; Fibroblasts; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Infant; Lysosomes; Male; Microscopy, Electron; Muscles; Organ Size

Intermittent high altitude hypoxia (8 hours a day, 5 days a week, stepwise up to the altitude of 7000 m, total number of exposures 24) induced in male and female rats, chronic pulmonary hypertension and right ventricular hypertrophy. No significant sex differences were found in both these parameters. A significant sex difference was demonstrated in the resistance of the cardiac muscle to acute anoxia in vitro: the myocardium of control female rats proved to be significantly more resistant to oxygen deficiency. Intermittent altitude hypoxia resulted in significantly enhanced resistance in both sexes, yet the sex difference was maintained. Sex differences were further observed in the growth response of experimental animals to the acclimatization process. Whereas the body weight of male rats exposed to intermittent altitude hypoxia was significantly lower, hypoxic females had body weights comparable to those of control animals.

Topics: Altitude; Animals; Body Weight; Cardiomegaly; Female; Glycogen; Hemodynamics; Hemoglobins; Hypertension, Pulmonary; Hypoxia; Male; Myocardial Contraction; Myocardium; Rats; Rats, Inbred Strains; Sex Factors

Riboxine stimulates activation of redox biosynthetic processes and raises aerobic production of energy in rat myocardium. Under pressure chamber hypoxia corresponding to the altitude 6000 m, riboxine promotes the correction of metabolic acidosis, normalization of the ultrastructure of cardiomyocytes and more balanced development of heart hypertrophy.

Topics: Adenosine Triphosphatases; Altitude Sickness; Animals; Cardiomegaly; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Energy Metabolism; Glycogen; Hypoxia; Inosine; L-Lactate Dehydrogenase; Myocardium; Rats; Succinate Dehydrogenase

We hypothesized that by inducing ventricular fibrillation (VF) prior to cardioplegic arrest in nonvented hypertrophied hearts of pigs, the metabolic characteristics of the epicardial and endocardial regions would be compromised compared with animals in which cardioplegic solution was infused while the hearts were in normal sinus rhythm (NSR). These abnormalities would be reflected not only in greater deterioration of myocardial metabolism after reperfusion in the VF group, but they would also be more pronounced in the subendocardial layers of hypertrophied left ventricles. Results obtained in hypothermic hearts (28 degrees C) maintained at 8 degrees to 12 degrees C during cardioplegic arrest demonstrated no major consistent differences in the stores of glycogen, creatine phosphate, adenine nucleotides, and lactate in both groups of hearts, for either layer of the left ventricular myocardium. The only significant difference was slightly lower creatine kinase content in the VF hearts than in the NSR group. It is concluded that induction of VF in hypothermic (28 degrees C), nonvented, hypertrophied hearts prior to infusion of cardioplegic solution does not affect myocardial energy stores compared with hearts in NSR, provided that the period of VF prior to clamping is short (3 minutes) and that the myocardial temperature is lowered to 28 degrees C prior to VF and is maintained at 8 degrees to 12 degrees C during cardioplegic arrest.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Cardiomegaly; Creatine Kinase; Glycogen; Heart Arrest, Induced; Hypothermia, Induced; Lactates; Lactic Acid; Myocardium; Swine; Ventricular Fibrillation

Topics: Adolescent; Adult; Age Factors; Cardiomegaly; Child; Child, Preschool; Glycogen; Heart Defects, Congenital; Humans; Infant; Microtubules; Mitochondria, Heart; Myocardium; Sarcoplasmic Reticulum

Rats were given a daily injection of L-epinephrine, 100 micrograms/100 g body wt, for 6 wk. The hearts of the epinephrine-treated animals were heavier (11.5%), and blood glucose and plasma insulin concentrations were lower than those of control rats. Acute responses to epinephrine were compared in the two groups. An increase in blood glucose and decreases in plasma insulin, liver glycogen, and muscle glycogen occurred in both groups. The magnitude of these responses were similar in the two groups except for the decrease in muscle glycogen, which was smaller in the chronic epinephrine-treatment group. There were no changes in respiratory capacity, citrate synthase or succinate dehydrogenase activities, or in cytochrome c concentration in skeletal muscle in response to 6 wk of epinephrine treatment. These results are compatible with the suggestion that catecholamines may play a role in some of the metabolic and cardiac adaptations to exercise training. However, they argue strongly against the hypothesis that catecholamines are responsible for inducing the increase in muscle mitochondria that occurs in response to exercise training.

Topics: Animals; Blood Glucose; Cardiomegaly; Epinephrine; Glycogen; Heart; Insulin; Lactates; Liver Glycogen; Male; Mitochondria, Muscle; Muscles; Rats

The myocardium of male Wistar rats aged 4, 24 and 33 months was examined using stereological techniques to determine the volume and surface densities of the ultrastructure of cardiac myocytes. Electron microscopy was used to detect succinate dehydrogenase in mitochondria. The myocardium of senescent animals was shown to be hypertrophied. The ratios of the volume densities of mitochondria, sarcoplasmic reticulum and T-system to the volume density of myofibrils in cardiac myocytes considerably decreased with age. The activity of succinate dehydrogenase in mitochondria reduced as well.

Topics: Aging; Animals; Cardiomegaly; Glycogen; Histocytochemistry; Male; Microscopy, Electron; Myocardium; Rats; Rats, Inbred Strains; Succinate Dehydrogenase

Topics: Amyloid; Calcium; Cardiomegaly; Cardiomyopathies; Collagen Diseases; Eosinophilia; Glycogen; Humans; Iron; Lipid Metabolism; Myocarditis; Myocardium; Sarcoidosis

Ultrastructural quantitative and qualitative investigations of the myocardium of 7 children with Fallot's disease and 3 children with a ventricular septal defect (VSD) have shown bizarre nuclei and a slight increase in the myofibril share of the volume (Fallot's disease: 51.22%; VSD: 56.85%). This may be interpreted as a sign of a cellular hypertrophy. The mitochondria have a proportion of 35.07% and 33.75%, respectively. The glycogen content is relatively high. The lipofuscin bodies originate mainly from mitochondria having a percentage of 1.43 and 1.67, respectively. Particular signs of a lesion could not be observed. From the ultrastructural findings on the morphology of heart muscle cells it can be deduced that operations of vitia may be safely carried out.

Topics: Adolescent; Cardiomegaly; Child; Child, Preschool; Female; Glycogen; Heart Septal Defects, Ventricular; Humans; Infant; Lipofuscin; Male; Microscopy, Electron; Mitochondria, Heart; Myocardium; Tetralogy of Fallot

An attempt was made to determine the effect of hypothermic potassium cardioplegia (35 mEq of potassium chloride) on the hypertrophic ventricle. Puppies with induced left ventricular hypertrophy were divided into four groups and studied after one hour on global ischemia. Myocardial adenosine triphosphate (ATP) was best preserved in the hypothermically perfused groups and correlated well with measurements of coronary sinus creatine phosphokinase (CPK). In Groups 1 and 2 (anoxic arrest at 37 degrees C and KC1 perfusion at 37 degrees C), CPK at 30 minutes of reperfusion was 1,031 and 198 IU, respectively, compared to 35 IU in Group 3 (KC1 perfusion at 4 degrees C) and 44 IU in Group 4 (Ringer's lactate at 4 degrees C). Myocardial injury was milder in Groups 3 and 4 regardless of whether potassium chloride was added. It is apparent that hypothermic perfusion of a hypertrophic ventricle was the major factor in myocardial preservation, as determined by myocardial ATP and coronary sinus CPK.

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Creatine Kinase; Disease Models, Animal; Dogs; Electrocardiography; Glycogen; Heart Arrest, Induced; Hypothermia, Induced; Lactates; Myocardial Contraction; Myocardium; Organ Size; Perfusion; Phosphocreatine; Potassium Chloride

Chest X-rays of 24 hypoglycemic newborns were compared with those of a matched control group of newborns with normal blood glucose levels. In the hypoglycemic group heart size was found to be significantly greater than in the control group. No correlation could be established between the degree of cardiomegaly and the severity of hypoglycemia. 19 of the 24 hypoglycemic children were prematures or small for dates and it is postulated that the low glycogen stores in these infants do not meet the metabolic demands of the myocardium during its postpartum circulatory adaptation.

Topics: Cardiomegaly; Glycogen; Humans; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Myocardium

Topics: Animals; Cardiomegaly; Energy Metabolism; Glycogen; Leucine; Male; Myocardial Contraction; Myocardium; Orotic Acid; Protein Biosynthesis; Rats; Uracil; Uridine

Ultrastructural studies were made of operatively resected crista supraventricularis muscle in 59 patients with congenital heart diseases, or whom 54 had obstruction to right ventricular outflow. Relationships of anatomic diagnosis, age, peripheral arterial oxygen saturation (PAO2), peak right ventricular systolic pressure gradient and right ventricular end-diastolic pressure (RVEDP) to hypertrophic changes, abnormalities of cellular and myofibrillar orientation, and degenerative alterations were determined. Changes directly related to hypertrophy were: cell diameters greater than 20 mu, irregular cell shape, lobulated nuclei, multiple intercalated discs, dilated T tubules, abnormal Z bands, and increased numbers of ribosomes. Abnormalities of cellular or myofibrillar orientation were focal in distribution and occurred in 12 patients, most of whom had elevated RVEDP, decreased PAO2, markedly enlarged cells, and interstitial fibrosis. Interstitial fibrosis was prominent in 19 patients and was associated with cellular hypertrophy, elevation of RVEDP, and increased age of the patients. Degenerative changes (myofibrillar lysis, abnormally small mitochondria, myelin figure formation, and proliferation of sarcoplasmic reticulum in cardiac muscle cells ocurred in six patients and correlated with increased age, decreased PAO2, and elevated RVEDP. Mitochondria containing glycogen deposits were present in 17 patients, most of whom had decreased PAO2. The variability of morphologic manifestations of chronic cardiac hypertrophy and the relationships of hypertrophic changes to orientation abnormalities and degenerative alterations are discussed.

Topics: Adolescent; Adult; Cardiomegaly; Cell Nucleus; Child; Child, Preschool; Collagen; Cytoplasmic Granules; Glycogen; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Humans; Hypertrophy; Microscopy, Electron; Microtubules; Middle Aged; Mitochondria, Muscle; Myocardium; Myofibrils; Pulmonary Valve; Pulmonary Valve Stenosis; Ribosomes; Sarcoplasmic Reticulum; Tetralogy of Fallot

Degenerated cardiac muscle cells were present in hypertrophied ventricular muscle obtained at operation from 12 (38%) of 32 patients with asymmetric septal hypertrophy (hypertrophic cardiomyopathy) or aortic valvular disease. Degenerated cells demonstrated a wide variety of ultrastructural alterations. Mildly altered cells were normal-sized or hypertrophied and showed focal changes, including preferential loss of thick (myosin) filaments, streaming and clumping of Z band material, and proliferation of the tubules of sarcoplasmic reticulum. Moderately and severely degenerated cells were normal-sized or atrophic and showed additional changes, including extensive myofibrillar lysis and loss of T tubules. The appearance of the most severely degenerated cells usually reflected the cytoplasmic organelle (sarcoplasmic reticulum, glycogen, or mitochondria) which underwent proliferation and filled the myofibril-free areas of these cells. Moderately and severely degenerated cells were present in areas of fibrosis, had thickened basement membranes, and had lost their intercellular connections. These observations suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with chronic ventricular hypertrophy.

Topics: Adolescent; Adult; Aortic Stenosis, Subvalvular; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiomegaly; Cell Membrane; Child; Female; Glycogen; Golgi Apparatus; Heart Septum; Heart Ventricles; Humans; Lipofuscin; Male; Middle Aged; Mitochondria, Muscle; Myocardium; Myofibrils; Ribosomes; Sarcolemma; Sarcoplasmic Reticulum

Heart hypertrophy was produced in rats by creating a coarctation of the aorta 4 months prior to the experiment. The conducted study of the contractile function and oxygen consumption in isolated working hearts demonstrated a marked decrease in the contractile function of the hypertrophied hearts, as compared to the intact ones. Oxygen utilization, however, remained in these preparations equal to that in the controls: hence, the efficacy of oxygen utilization per unit of function was decreased. At the same time, the process of mobilization--glycogen re-synthesis--is highly activated, and glycolysis--accelerated. In order to explain these phenomena it was postulated that the falling efficacy of oxygen utilization and glycogenolysis activation may be caused by a growing calcium concentration in the myoplasm due to the progressive decrease of the capacity of the calcium pump of the sarcoplasmatic reticulum in the process of heart hypertrophy development.

Topics: Animals; Cardiomegaly; Glycogen; Heart; Male; Myocardial Contraction; Myocardium; Oxygen Consumption; Rats

Severe cardiac hypertrophy has been produced experimentally in rats by long-term, low-dose treatment with tri-iodothyroacetic acid. The dose used was insufficient to cause any apparent systemic or metabolic effect. It is suggested that similar iodinated substances in the blood in man, resulting from normal or abnormal thyroid hormone catabolism, may be causally related to some forms of cardiomyopathy.

Topics: Acetates; Acid Phosphatase; Alkaline Phosphatase; Animals; Cardiomegaly; Disease Models, Animal; Glycogen; Heart; Heart Ventricles; Mitochondria, Muscle; Myocardium; Organ Size; Rats; Succinate Dehydrogenase; Triiodothyronine

Adding 900 p.p.m. silver (as silver nitrate) to a practical diet for chicks significantly depressed growth, increased wet and dry heart weight to body weight ratios and markedly increased mortality during a four-week experimental period. Blood packed cell volume was not affected. Supplementing the diet containing silver with 50 p.p.m. copper prevented cardiac enlargement and mortality, but only partially corrected the growth depression. Glycogen content of the heart was not affected, but aortic elastin content was significantly reduced by silver and restored to normal by supplemental copper. Dietary silver significantly reduced the copper content of blood, spleen, brain, liver, but except for the brain, the level of copper in these tissues was restored to normal by dietary copper supplementation. No significant differences in copper content of kidney tissue were observed among the treatment. Copper content of the excreta was not significantly increased by adding dietary silver, but was greatly increased by adding 50 p.p.m copper to the diet containing silver.

Topics: Administration, Oral; Animals; Aorta; Brain; Cardiomegaly; Chickens; Copper; Diet; Elastin; Glycogen; Kidney; Liver; Myocardium; Poultry Diseases; Silver; Spleen

Topics: Adult; Animals; Cardiomegaly; Cell Nucleus; Child; Glycogen; Heart Diseases; Histocytochemistry; Humans; Male; Mice; Middle Aged; Myocardium; Phosphorylases; Rats

Topics: Adolescent; Adult; Aged; Aortic Valve Stenosis; Cardiomegaly; Child; Female; Glycogen; Humans; Male; Middle Aged; Mitochondria, Muscle; Mitochondrial Swelling; Myocardium

Topics: Aortic Valve Insufficiency; Cardiomegaly; Cardiomyopathy, Hypertrophic; Glycogen; Histocytochemistry; Humans; Myocardium

Topics: Adolescent; Adult; Aged; Biopsy; Cardiomegaly; Cardiomyopathy, Hypertrophic; Child; Female; Glycogen; Heart Septum; Heart Ventricles; Humans; Intercellular Junctions; Male; Microscopy, Electron; Middle Aged; Mitochondria; Myocardium; Myofibrils; Ribosomes; Sarcoplasmic Reticulum

Topics: Acid Phosphatase; Cardiomegaly; Cardiomyopathies; Esterases; Glycogen; Humans; Lysosomes; Microscopy, Electron; Mitochondria, Muscle; Myocardial Contraction; Myocardium; NADH, NADPH Oxidoreductases

Topics: Autopsy; Brain; Carbohydrate Metabolism, Inborn Errors; Cardiomegaly; Cardiomyopathies; Child; Digestive System; Glycogen; Glycogen Storage Disease; Glycosaminoglycans; Histocytochemistry; Humans; Kidney; Liver; Lung; Male; Microscopy, Electron; Muscle, Smooth; Muscles; Myocardium; Polysaccharides; Spleen

Topics: Adult; Cardiomegaly; Female; Glycogen; Heart Ventricles; Humans; Male; Middle Aged; Myocardium

Topics: Adenosine Monophosphate; Adenosine Triphosphatases; Animals; Cardiomegaly; Electrolytes; Glycogen; Humans; Myocardium

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: Carbon Isotopes; Cardiomegaly; Cell Line; Chromatography, Paper; Disaccharides; Fibroblasts; Glucose; Glucosidases; Glycogen; Glycogen Storage Disease; Half-Life; Heart Defects, Congenital; Heart Diseases; Humans; Skin

Topics: Biopsy; Cardiomegaly; Child, Preschool; Glucosidases; Glycogen; Glycogen Storage Disease; Heart Defects, Congenital; Heart Diseases; Humans; Male; Microscopy, Electron; Oculomotor Muscles

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: Animals; Cardiomegaly; Chromatography, Gel; Cross Reactions; Female; Glucosidases; Glycogen; Glycogen Storage Disease; Heart Defects, Congenital; Heart Diseases; Humans; Hydrogen-Ion Concentration; Hydrolysis; Immunodiffusion; Immunoglobulins; Kinetics; Liver; Lysosomes; Maltose; Mice; Placenta; Pregnancy; Rabbits; Rats

Topics: Animals; Autoradiography; Cardiomegaly; Cell Nucleus; Chromatin; DNA; Edema; Glycogen; Histocytochemistry; Hypertrophy; Injections, Intraperitoneal; Isoproterenol; Male; Microscopy; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Necrosis; Rats; Ribosomes; RNA; Sarcoplasmic Reticulum; Time Factors

Topics: Adaptation, Physiological; Animals; Cardiomegaly; Glycogen; Hypoxia; Myocardium; Rats

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: Animals; Cardiomegaly; Glucosidases; Glycogen; Glycogen Storage Disease; Heart Defects, Congenital; Heart Diseases; Male; Microscopy, Electron; Rats; Syndrome

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: Biopsy; Cardiomegaly; Diagnosis, Differential; Glucose-6-Phosphatase; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Heart Defects, Congenital; Heart Diseases; Humans; Infant; Liver; Male; Methods; Muscles; Muscular Diseases; Skin

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: Age Factors; Animals; Cardiomegaly; Cardiomyopathies; Cell Nucleus; Cricetinae; Cytoplasmic Granules; Disease Models, Animal; Endoplasmic Reticulum; Female; Glycogen; Golgi Apparatus; Male; Microscopy, Electron; Mitochondria; Mitosis; Ribosomes; Sarcolemma

Topics: Adolescent; Cardiomegaly; Cardiomyopathies; Diagnosis, Differential; Electrocardiography; Fluorescent Antibody Technique; Glycogen; Humans; Hyperplasia; Male; Microscopy, Electron; Muscle Proteins; Myocardium; Myofibrils; Sarcolemma

Topics: Acridines; Animals; Autolysis; Autopsy; Cardiomegaly; Clinical Enzyme Tests; Coronary Disease; Death, Sudden; Diagnosis, Differential; Forensic Medicine; Glycogen; Humans; Hydrogen-Ion Concentration; Microscopy, Fluorescence; Myocardial Infarction; Myocardium; Oxidoreductases; Staining and Labeling; Swine

Topics: Animals; Aortic Valve Stenosis; Cardiomegaly; Dogs; Glycogen; Golgi Apparatus; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Myofibrils; Ribosomes; RNA

Topics: Adenosine Triphosphate; Animals; Carbon Isotopes; Cardiomegaly; Glycogen; Glycolysis; Hydrogen-Ion Concentration; In Vitro Techniques; Lactates; Methods; Muscle Contraction; Myocardium; Oxidative Phosphorylation; Oxygen Consumption; Rats; Tissue Extracts

Topics: Animals; Cardiomegaly; Dogs; Glycogen; Heart Ventricles; Histocytochemistry; Hypertrophy; Microscopy, Electron; Myocardium; Myofibrils; Pulmonary Artery

Topics: Biopsy; Brain; Cardiomegaly; Child; Cytoplasm; Epinephrine; Female; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Kidney; Liver; Lung; Microscopy, Electron; Muscles; Myocardium

Topics: Animals; Cardiomegaly; Chick Embryo; DNA; Electrocardiography; Glycogen; Glycogen Storage Disease; Histocytochemistry; Hypertrophy; Microscopy, Electron; Models, Theoretical; Myocardium; Proteins; Temperature

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

Topics: Adolescent; Adult; Aged; Aging; Amyloid; Calcium; Carbohydrate Metabolism; Cardiomegaly; Child; Child, Preschool; DNA; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Methods; Middle Aged; Myocardium; Polysaccharides; Proteins

Topics: Adrenal Glands; Animals; Blood Cell Count; Cardiomegaly; Cardiovascular System; Catecholamines; Electrocardiography; Epinephrine; Glycogen; Heart; Hemoglobins; Hyperthyroidism; Hypertrophy; Myocardium; Nitrogen; Norepinephrine; Organ Size; Protein Biosynthesis; Rabbits; Thyroid Hormones; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Glycogen; Male; Models, Theoretical; Physical Exertion; Rats; Trichloroacetic Acid

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: Adrenocorticotropic Hormone; Animals; Cardiomegaly; Glycogen; Glycogenolysis; Growth Hormone; Heart; Human Growth Hormone; Myocardium; Rats

Topics: Aortic Valve Stenosis; Cardiomegaly; Glycogen; Glycogenolysis; Hypertrophy, Left Ventricular; Myocardium; Vascular Resistance

Topics: Animals; Cardiomegaly; Glycogen; Glycogenolysis; Hypertrophy; Myocardium; Rats

Topics: Cardiomegaly; Glycogen; Glycogen Storage Disease; Heart; Humans

Topics: Cardiomegaly; Glycogen; Glycogenolysis; Humans