glycogen and Cardiomyopathies

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

Glycogen storage disorders (GSDs) are inborn errors of metabolism with abnormal storage or utilization of glycogen. The present review focuses on recent advances in hepatic GSD types I, III and VI/IX, with emphasis on clinical aspects and treatment.. Evidence accumulates that poor metabolic control is a risk factor for the development of long-term complications, such as liver adenomas, low bone density/osteoporosis, and kidney disease in GSD I. However, mechanisms leading to these complications remain poorly understood and are being investigated. Molecular causes underlying neutropenia and neutrophil dysfunction in GSD I have been elucidated. Case series provide new insights into the natural course and outcome of GSD types VI and IX. For GSD III, a high protein/fat diet has been reported to improve (cardio)myopathy, but the beneficial effect of this dietary concept on muscle and liver disease manifestations needs to be further established in prospective studies.. Although further knowledge has been gained regarding pathophysiology, disease course, treatment, and complications of hepatic GSDs, more controlled prospective studies are needed to assess effects of different dietary and medical treatment options on long-term outcome and quality of life.

Topics: Animals; Cardiomyopathies; Diet, Carbohydrate-Restricted; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Disease Models, Animal; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; Humans; Liver; Liver Cirrhosis

Glucocorticoids include steroid hormones released from the adrenal cortex or synthetic analogues developed for various inflammatory and immune disorders. GCs are known to play an important role in maintaining the body's metabolic balance, but their irregular activity has been associated with complications like Cushing's syndrome, insulin resistance, and heart disease. Conventional GC action is through their nuclear receptor activation, but specific and non-specific membrane bound receptor mediated non-genomic actions have also been reported. GCs increase AMPK phosphorylation at Thr172, in addition to augmenting AMPK protein and gene expressions. AMPK is insulin mimetic in many of its actions like glucose uptake and inhibition of lipolysis, and these properties of AMPK are made used in conditions like insulin resistance and diabetes. Nevertheless, if AMPK is activated by GC in the absence of diabetes or decreased insulin signaling, accumulation of substrates in the form of glycogen and triglycerides could precipitate cardiac abnormalities. Glycogen storage can lead to many disorders like hypertrophy, conduction system disease and Wolff Parkinson White syndrome. TG accumulation is associated with generation of free radicals, ceramide formation, mitochondrial dysfunction and cardiac cell death. In this review, we outline the cardiometabolic changes associated with GC, especially related to augmentation in AMPK, and link these changes to cardiac dysfunction.

Topics: Adrenal Cortex; Adrenocortical Hyperfunction; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cardiomyopathies; Enzyme Activation; Glucocorticoids; Glucose; Glycogen; Heart; Humans; Lipid Metabolism; Myocardium; Triglycerides; Up-Regulation

Metabolic cardiomyopathy of babies and children accounts for approximately 15% of all cardiomyopathies presenting at these ages. The confirmation of the aetiology is essential for treatment, which is rarely curative. For establishing a prognosis which is often poor, and, above all, for family counselling in cases of mendelian transmission or mitochondrial disease. Cardiomyopathy due to glycogen (Pompe's disease) or mucopolysaccharide (Hurler's disease) disorders are easy to diagnose because of obvious extracardiac manifestations. The diagnosis of the enzyme deficiency only requires a blood and/or urine test. Cardiomyopathies due to a deficit of oxidative metabolism are usually associated with multi-system abnormalities but may be isolated or the presenting sign of the deficit. The diagnosis should be suspected in cases of a positive family history of cardiomyopathy or sudden death, of co-sanguinity, of unusual or unexplained extracardiac disease, of atypical ECG changes or of hypoglycaemia. Chromatography of organic acids, analysis of acylcarnitines and -oxidation of the fatty acid oxidation. Of these conditions, only primary carnitine deficits are curable. The diagnosis of mitochondrial cardiomyopathy is based on the ratios of oxidoreduction and, above all, on spectrophotometric analysis of the respiratory chain complexes in skeletal or cardiac muscle (when the heart is the only organ involved). Genetic counselling is difficult and punctual mutations or deletions of mitochondrial DNA are rarely observed, and also few nuclear genes coding for the proteins of the respiratory chain have been identified to this day.

Topics: Cardiomyopathies; Child; Child, Preschool; Diagnosis, Differential; Electrocardiography; Family Health; Female; Genetic Counseling; Glycogen; Glycogen Storage Disease Type II; Humans; Infant; Infant, Newborn; Male; Mitochondrial Myopathies; Mucopolysaccharidosis I

Round heart disease (RHD) is a spontaneous occurring cardiomyopathy in fowl affecting primarily inbred, small broad-breasted white strains of turkeys. Etiology of RHD is unknown but factors implicated include genetic, management, enzyme deficiencies, viral, immunologic, and metabolic. Investigations of proposed etiologic factors are reviewed. Furazolidone (FZ)-induced cardiomyopathy is indistinguishable from spontaneous RHD, but it remains to be shown that both are mediated by the same mechanism(s). Studies to date suggest that FZ-induced cardiomyopathy is an exaggeration of the spontaneous condition.

Topics: Aging; Animals; Blood Proteins; Calcium; Cardiomyopathies; Cortisone; Electrocardiography; Female; Furazolidone; Glycogen; Hemodynamics; Humans; Male; Poultry Diseases; Sodium; Stress, Physiological; Turkeys; Vectorcardiography; Virus Diseases

The pharmacological and toxicological properties of furazolidone have been briefly reviewed. Among the most important pharmacological actions of furazolidone is the inhibition of mono- and diamine oxidase activities, which seem to depend, at least in some species, on the presence of the gut flora. The drug also seems to interfere with the utilization of thiamin, which is probably instrumental in the production of anorexia and loss of body weight of the treated animals. Furazolidone is known to induce a condition of cardiomyopathy in turkeys, which could be used as a model to study alpha 1-antitrypsin deficiency in man. The drug is most toxic to ruminants. The toxic signs observed were of nervous nature. Experiments are in progress in this laboratory to try to explain the mechanism(s) by which this toxicity is brought about. It is uncertain whether the use of furazolidone at the recommended therapeutic dose would result in drug residues in tissues of treated animals. This is a matter of public health importance as the drug has been shown to possess a carcinogenic activity. It is important that a simple and reliable method of identification and estimation of furazolidone residues be devised. More work is needed to elucidate the mode of action and biochemical effects caused by the drug in both the host and the infective organisms.

Topics: Adrenal Glands; Alcoholism; Animals; Anorexia; Brain; Cardiomyopathies; Cattle; Chick Embryo; Chickens; Chromatography, High Pressure Liquid; Ducks; Female; Furazolidone; Glycogen; Guinea Pigs; Humans; In Vitro Techniques; Liver; Mice; Monoamine Oxidase Inhibitors; Poultry Diseases; Pregnancy; Rabbits; Rats; Thiamine Deficiency; Turkeys

Topics: Cardiomyopathies; Fibroblasts; Glucose; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infusions, Parenteral; Leukocytes; Liver; Male; Maltose; Microscopy, Electron; Muscles; Placenta; Skin; Syndrome

Topics: Cardiomyopathies; Glucosephosphate Dehydrogenase Deficiency; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Hepatomegaly; Humans; Kidney Diseases; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Muscular Diseases; Pectins; Polysaccharides; Splenomegaly

Topics: Cardiomyopathies; Cell Membrane; Glycogen; Mitochondria; Muscle Contraction; Myocardium; Myofibrils; Myoglobin

Pathogenic missense variants in PRKAG2, the gene for the gamma 2 regulatory subunit of adenosine monophosphate-activated protein kinase (AMPK), cause severe progressive cardiac disease and sudden cardiac death, named PRKAG2 cardiomyopathy. In our previous study, we reported a E506K variant in the PRKAG2 gene that was associated with this disease. This study aimed to functionally characterize the three missense variants (E506K, E506Q, and R531G) of PRKAG2 and determine the possible effects on AMPK activity.. The proband was clinically monitored for eight years. To investigate the functional effects of three missense variants of PRKAG2, in vitro mutagenesis experiments using HEK293 cells with wild and mutant transcripts and proteins were comparatively analyzed using quantitative RT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay.. In the long-term follow-up, the proband was deceased due to progressive heart failure. In the in vitro experimental studies, PRKAG2 was overexpressed after 48 h of transfection in three mutated cells, after which the expression levels of PRKAG2 were regressed to the level of wild-type cells in 3-weeks stably transformed cells, except for the cells with E506K variant. E506K, E506Q, and R531G variants had caused a reduction in the AMPK activity and resulted in the formation of cytoplasmic glycogen deposits.. Three missense variants that alter AMPK activity affect a residue in the CBS4 domain associated with ATP/AMP-binding. Detailed information on the influence of PRKAG2 pathogenic variants on AMPK activity would be helpful to improve the treatment and management of patients with metabolic cardiomyopathy.

Topics: AMP-Activated Protein Kinases; Cardiomyopathies; Glycogen; HEK293 Cells; Humans; Mutation; Mutation, Missense; Transcription Factors

Many reports have been published recently confirmed the limitation of cargo molecules delivered into the heart. This failure is mostly associated with lymphatic or vascular channels washing or to the immune system recognition. Delivery of anthocyanins by encapsulation may augment it retention in the heart at early time points as the capsules are too large to wash out by lymphatic or venous channels and the physical structure of the capsule may shield the anthocyanins from immunoglobulins and cellular components of the immune system. In the current study, the cardiac dysfunction was induced by using carbon tetrachloride and then animal were treated orally by using anthocyanins incorporated into hydrogel NPs twice time /week for 4 weeks. The results showed anthocyanin loaded hydrogel NPs has ability to re-maintain the glycogen content in the liver and heart tissues of fibrotic group (13 ± 1.4 and 5 ± 0.7 μmol glucose/g tissue). Additionally, MDA and hydroxyproline were significantly reduced. PAS stain showed depletion of glycogen granules from heart tissue. It is concluded that starch based hydrogel loaded by anthocyanins can improve histological cardiac functions after their injury .

Topics: Animals; Anthocyanins; Carbon Tetrachloride; Cardiomyopathies; Cardiotoxicity; Disease Models, Animal; Drug Compounding; Fibrosis; Glycogen; Hydrogels; Liver; Mice; Myocytes, Cardiac; Nanoparticles; Starch

T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD

Topics: Animals; Cardiomyopathies; Cardiotoxicity; Glycogen; Male; Mast Cells; Myocardium; Myocytes, Cardiac; Rats, Wistar; T-2 Toxin

PIMT/NCOA6IP, a transcriptional coactivator PRIP/NCOA6 binding protein, enhances nuclear receptor transcriptional activity. Germline disruption of PIMT results in early embryonic lethality due to impairment of development around blastocyst and uterine implantation stages. We now generated mice with Cre-mediated cardiac-specific deletion of PIMT (csPIMT

Topics: Animals; Cardiomyopathies; Cardiomyopathy, Dilated; Disease Models, Animal; Energy Metabolism; Fibrosis; Gene Deletion; Gene Expression; Glucose; Glycogen; Mice; Mice, Knockout; Mitochondria; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Nuclear Receptor Coactivators; Protein D-Aspartate-L-Isoaspartate Methyltransferase

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Dual-Specificity Phosphatases; Echocardiography; Glycogen; Humans; Lafora Disease; Mice; Mice, Knockout; Mutation; Myocytes, Cardiac; Protein Tyrosine Phosphatases, Non-Receptor; Seizures; Stroke Volume; Ubiquitin-Protein Ligases; Ventricular Dysfunction, Left; Ventricular Remodeling

We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha-amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.

Topics: Adult; Biopsy; Cardiomyopathies; Glucans; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycoproteins; Homozygote; Humans; Male; Middle Aged; Muscle, Skeletal; Mutation, Missense

Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MI

Topics: AMP-Activated Protein Kinases; Animals; Blotting, Western; Cardiomyopathies; Cell Respiration; Cicatrix; Coronary Stenosis; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex IV; Glucose Transport Proteins, Facilitative; Glycogen; Magnetic Resonance Imaging; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria, Heart; Myocardial Infarction; Myocardial Perfusion Imaging; Myocytes, Cardiac; Oxygen Consumption; Real-Time Polymerase Chain Reaction; RNA, Messenger; Stroke Volume; Sus scrofa; Swine; Ventricular Remodeling

AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, and ventricular pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show that activating PRKAG2 mutations increase microtissue twitch force by enhancing myocyte survival. Integrating RNA sequencing with metabolomics, PRKAG2 mutations that activate AMPK remodeled global metabolism by regulating RNA transcripts to favor glycogen storage and oxidative metabolism instead of glycolysis. As in patients with PRKAG2 cardiomyopathy, iPS cell and mouse models are protected from cardiac fibrosis, and we define a crosstalk between AMPK and post-transcriptional regulation of TGFβ isoform signaling that has implications in fibrotic forms of cardiomyopathy. Our results establish critical connections among metabolic sensing, myocyte survival, and TGFβ signaling.

Topics: AMP-Activated Protein Kinases; Animals; Cardiomyopathies; Cell Survival; Glycogen; Humans; Hypertrophy, Left Ventricular; Induced Pluripotent Stem Cells; Metabolome; Mice; Muscle Cells; Mutation, Missense; Sequence Analysis, RNA; Signal Transduction; Tissue Engineering; Transforming Growth Factor beta1

Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme (GAA; EC.3.2.1.3) leading to intracellular aggregations of glycogenin muscles. The infantile-onset type is the most life-threatening form of this disease, in which most of patients suffer from cardiomyopathy and hypotonia in early infancy. In this study, a typical case of Pompe disease was reported in an Iranian patient using molecular analysis of the GAA gene. Our results revealed a new c.1824_1828dupATACG mutation in exon 13 of the GAA gene. In conclusion, with the finding of this novel mutation, the genotypic spectrum of Iranian patients with Pompe disease has been extended, facilitating the definition of disease-related mutations.

Topics: alpha-Glucosidases; Cardiomyopathies; Consanguinity; Exons; Genetic Predisposition to Disease; Genome-Wide Association Study; Genome, Human; Genotype; Genotyping Techniques; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease Type II; Humans; Infant; Iran; Male; Mutation; Oligosaccharides; Sequence Analysis, DNA

To determine whether newborn screening facilitates early detection and thereby early treatment initiation for later-onset Pompe disease.. We have conducted a newborn screening program since 2005. Newborns with deficient skin fibroblast acid α-glucosidase activity and two acid α-glucosidase gene mutations but no cardiomyopathy were defined as having later-onset Pompe disease, and their motor development and serum creatine kinase levels were monitored every 3 to 6 months.. Among 344 056 newborns, 13 (1 in 26 466) were found to have later-onset Pompe disease. During a follow-up period of up to 4 years, four patients were treated because of hypotonia, muscle weakness, delayed developmental milestones/motor skills, or elevated creatine kinase levels starting at the ages of 1.5, 14, 34, and 36 months, respectively. Muscle biopsy specimens obtained from the treated patients revealed increased storage of glycogen and lipids.. Newborn screening was found to facilitate the early detection of later-onset Pompe disease. A subsequent symptomatic approach then identifies patients who need early treatment initiation.

Topics: Adolescent; Adult; alpha-Glucosidases; Biopsy; Cardiomyopathies; Creatine Kinase; Enzyme Replacement Therapy; Female; Fibroblasts; Glycogen; Glycogen Storage Disease Type II; Humans; Infant, Newborn; Lipids; Male; Middle Aged; Mutation; Neonatal Screening; Skin

Topics: Animals; Cardiomyopathies; Codon, Nonsense; Diabetes Mellitus, Type 2; Exercise; Frameshift Mutation; Gene Frequency; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Heart; Humans; Infant, Newborn; Insulin; Insulin Resistance; Mice; Muscle, Skeletal; Myocardium; Organ Specificity; Phosphoprotein Phosphatases; United Kingdom; White People

AMP-activated protein kinase (AMPK) responds to impaired cellular energy status by stimulating substrate metabolism for ATP generation. Mutation of the gamma2 regulatory subunit of AMPK in humans renders the kinase insensitive to energy status and causes glycogen storage cardiomyopathy via unknown mechanisms. Using transgenic mice expressing one of the mutant gamma2 subunits (N488I) in the heart, we found that aberrant high activity of AMPK in the absence of energy deficit caused extensive remodeling of the substrate metabolism pathways to accommodate increases in both glucose uptake and fatty acid oxidation in the hearts of gamma2 mutant mice via distinct, yet synergistic mechanisms resulting in selective fuel storage as glycogen. Increased glucose entry in the gamma2 mutant mouse hearts was directed through the remodeled metabolic network toward glycogen synthesis and, at a substantially higher glycogen level, recycled through the glycogen pool to enter glycolysis. Thus, the metabolic consequences of chronic activation of AMPK in the absence of energy deficiency is distinct from those previously reported during stress conditions. These findings are of particular importance in considering AMPK as a target for the treatment of metabolic diseases.

Topics: Amino Acid Substitution; AMP-Activated Protein Kinases; Animals; Cardiomyopathies; Disease Models, Animal; Energy Metabolism; Enzyme Activation; Glycogen; Glycogen Storage Disease; Humans; Mice; Multienzyme Complexes; Myocardium; Oxidative Stress; Protein Serine-Threonine Kinases; Substrate Cycling; Up-Regulation

Investigation of ethiology, pathogenesis, morphogenesis, pathokinesis, treatment and prevention of cardiomyopathy is one of the most important problems of cardiology. Last years many scientific forums have been devoted to cardiomyopathy problems and still many issues remain disputable and needs further investigation and definition. In particular, investigation of metabolic processes in cardiac muscle seems of great importance. Obtained data will promote elaboration of adequate means toward the correction of cardiac decompensation during cardiomyopathy. The main goal of present study was the investigation of oxidation-reduction and electron transport associated protein activity in myocardium during experimental cardiomyopathy. Experiments were carried out on 30 male rats (180 - 200 g weight). Based on histological, histochemical, enzymehistological investigations conclusion has been made that during experimental autoimmune cardiomyopathy activity of oxidation-reduction and electron transport enzymes is sharply decreased along with the decrease of ascorbic acid and tiny granule glycogen amount (with altered topographic distribution) determining energy deficiency and weakening of cardiac muscle contractile function. It is possible to consider that the present study will open the way for future research and prompt us to select optimal therapeutic agents.

Topics: Animals; Ascorbic Acid; Cardiomyopathies; Electron Transport; Glycogen; Male; Myocardium; Oxidation-Reduction; Rats; Rats, Inbred Strains; Succinate Dehydrogenase

We investigated the role of the kallikrein-kinin system in cardiac function and glucose utilization in the streptozotocin (STZ)-induced diabetic rat model using a gene transfer approach. Adenovirus harboring the human tissue kallikrein gene was administered to rats by intravenous injection at 1 week after STZ treatment. Human kallikrein transgene expression was detected in the serum and urine of STZ-induced diabetic rats after gene transfer. Kallikrein gene delivery significantly reduced blood glucose levels and cardiac glycogen accumulation in STZ-induced diabetic rats. Kallikrein gene transfer also significantly attenuated elevated plasma triglyceride and cholesterol levels, food and water intake, and loss of body weight gain, epididymal fat pad, and gastrocnemius muscle weight in STZ-induced diabetic rats. However, these effects were blocked by icatibant, a kinin B2 receptor antagonist. Cardiac function was significantly improved after kallikrein gene transfer as evidenced by increased cardiac output and +/-delta P/delta t (maximum speed of contraction/relaxation), along with elevated cardiac sarco(endo)plasmic reticulum (Ca2+ + Mg2+)-ATPase (SERCA)-2a, phosphorylated phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes of cardiac and skeletal muscle. Kallikrein gene delivery also increased Akt and glycogen synthase kinase (GSK)-3beta phosphorylation, resulting in decreased GSK-3beta activity in the heart. These results indicate that kallikrein through kinin formation protects against diabetic cardiomyopathy by improving cardiac function and promoting glucose utilization and lipid metabolism.

Topics: Adenoviridae; Animals; Blood Glucose; Cardiomyopathies; Diabetes Mellitus, Experimental; Disease Models, Animal; Genetic Vectors; Glycogen; Humans; Kallikreins; Lipids; Male; Myocardium; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Transfection

Danon disease (DD) is a rare lysosomal glycogen storage disease with normal acid maltase activity, which is characterised clinically by cardiomyopathy and myopathy, and a variable degree of mental retardation. The causative gene, LAMP2, has been mapped to chromosome Xq24-q25. LAMP2 encodes a lysosome-associated membrane glycoprotein. We identified a novel LAMP2 mutation of the exon 8 splice acceptor site (IVS7-1G --> A) in an affected male and female, which predicts abnormal splicing. Both affected individuals presented solely with hypertrophic cardiomyopathy. Muscle weakness and mental impairment were absent. Diagnosis of Danon disease was established by muscle biopsy, when the male index patient developed transient severe muscle weakness following heart transplantation. Typical biopsy findings were also found in a heart muscle specimen. Demonstration of the LAMP2 mutation in affected male and female siblings is compatible with X-linked dominant inheritance. Danon disease should be actively looked for in cardiomyopathy patients.

Topics: Adult; Antigens, CD; Cardiomyopathies; Chromosomes, Human, X; DNA Mutational Analysis; Exons; Female; Glycogen; Glycogen Storage Disease Type II; Heart Transplantation; Humans; Lysosomal Membrane Proteins; Lysosomal-Associated Membrane Protein 2; Male; Muscle, Skeletal; Muscle, Smooth; Point Mutation

Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease. We have addressed the issue of reversibility of the disease in the Gaa(-/-) mouse model. We have made transgenic lines expressing human GAA in skeletal and cardiac muscle of Gaa(-/-) mice, and we turned the transgene on at different stages of disease progression by using a tetracycline-controllable system. We have demonstrated that levels of 20-30% of normal activity are indeed sufficient to clear glycogen in the heart of young Gaa(-/-) mice, but not in older mice with a considerably higher glycogen load. However, in skeletal muscle-a major organ affected in infantile and in milder, late-onset variants in humans-induction of GAA expression in young Gaa(-/-) mice to levels greatly exceeding wildtype values did not result in full phenotypic correction, and some muscle fibers showed little or no glycogen clearance. The results demonstrate that complete reversal of pathology in skeletal muscle or long-affected heart muscle will require much more enzyme than previously expected or a different approach.

Topics: alpha-Glucosidases; Animals; Blotting, Western; Cardiomyopathies; Female; Gene Transfer Techniques; Glycogen; Glycogen Storage Disease Type II; Humans; Mice; Mice, Knockout; Mice, Transgenic; Muscle, Skeletal; Mutation; Myocardium; Phenotype; Transgenes

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

The activity of the beta isoform of protein kinase C (PKC beta) is reduced in the diabetic heart. Since this isozyme has been implicated in insulin action, we tested the hypothesis that PKC beta contributes to the development of impaired glucose metabolism by the noninsulin-dependent diabetic heart. Exposure of the diabetic heart to buffer containing the protein kinase C activator, phorbol myristate acetate, increased PKC beta activity in the membrane. Associated with the improvement in PKC beta activity was a biphasic change in glucose metabolism. The initial phase was characterized by a breakdown in glycogen stores, a stimulation in glucose oxidation and a decrease in endogenous fatty acid oxidation. This was followed by a second phase in which the uptake of glucose was modestly stimulated. Nonetheless, since the phorbol ester did not overcome the diabetes-linked defect in pyruvate dehydrogenase, the increase in glycolytic flux was not associated with a rise in glucose oxidation. Consequently, nearly 50% of the triose units were diverted into lactate and pyruvate production and the generation of ATP from glucose was restricted. Since insulin promotes not only glucose uptake, but also glycogen synthesis and glucose oxidation, the phorbol ester and insulin effects are very different. Thus, the data do not support a role for PKC beta in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.

Topics: Animals; Carcinogens; Cardiomyopathies; Diabetes Mellitus, Experimental; Glucose; Glycogen; Heart; Protein Kinase C; Tetradecanoylphorbol Acetate

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.

Topics: Adolescent; Adult; Basement Membrane; Biopsy; Cardiomyopathies; Cell Membrane; Dystrophin; Glycogen; Humans; Immunohistochemistry; Intellectual Disability; Male; Microscopy, Electron; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Sarcolemma; Staining and Labeling; Vacuoles

The aim of the present experimental study in the rat heart was to assess cardiac performance and metabolism in mild diabetes of 2 months' duration (postprandial blood sugar levels of 307 +/- 101 mg/dl and nearly normal fasting blood glucose of 102 +/- 40 mg/dl) using the working rat heart model at physiological workload with a perfusion time of 60 min. We also compared the effect of two forms of therapy for diabetes, islet transplantation and insulin therapy (s.c.), after 2 months. A 36% reduction in glucose utilization is metabolically characteristic for the diabetic heart, mainly caused by a 55% reduced glucose uptake (P < 0.001), but also by a nearly twofold increased lactate and pyruvate production (P < 0.001). This reduced carbohydrate metabolism is accompanied by a 37% reduction of oxygen uptake (P < 0.001) as well as a significant reduction in myocardial ATP and CP levels (P < 0.001), resulting in a significantly reduced cardiac output (P < 0.001). Moreover, the balance of energy reveals that the diabetic heart obtains 46% of its energy requirements for 1 h from endogenous glycogen, whereas the control heart obtains 91% of its energy needs (i.e. preferentially) from exogenous glucose (only 9% from endogenous glycogen). Both investigated therapeutic interventions led to a complete reversibility of the hemodynamic and metabolic alterations, indicating that the cause of diabetic cardiomyopathy in this model of mild and short-term diabetes is due to a defect in cardiac carbohydrate metabolism, which is correctable by insulin administration.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Cardiac Output; Cardiomyopathies; Diabetes Mellitus, Experimental; Energy Metabolism; Glucose; Glycogen; In Vitro Techniques; Insulin; Islets of Langerhans Transplantation; Lactates; Male; Myocardium; Oxygen Consumption; Phosphocreatine; Pyruvates; Rats; Rats, Inbred Lew; Triglycerides; Ventricular Dysfunction, Left

A 21-year-old man with childhood-onset mental retardation, non-obstructive hypertrophic cardiomyopathy, and vacuolar myopathy is presented. A histopathological study of biopsied skeletal muscle showed lysosomal glycogen storage mimicking acid maltase deficiency, but biochemical analysis showed normal acid alpha-glucosidase activity. Glycogenosomes were also recognized in endothelial cells on electronmicroscopic examination of biopsied skeletal muscle. Magnetic resonance imaging (MRI) findings in the head revealed the involvement of the central nervous system. This is a new type of lysosomal glycogen storage disease with multisystemic involvement. The specific biochemical defect in this disorder remains to be elucidated.

Topics: Adult; alpha-Glucosidases; Autophagy; Brain; Cardiomyopathies; Glycogen; Glycogen Debranching Enzyme System; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Muscles; Muscular Diseases; Syndrome; Vacuoles

A recirculating, retrograde heart perfusion according to Langendorff is described as a method for the evaluation of cardiomyopathy as an untoward side effect of a high lipid diet (addition of 10% and 25% corn oil to rat maintenance feed) in female rats. The use of glucose (5 mM) or palmitate (0.5 mM/0.1 mM BSA) as substrates during a 2-h perfusion period, and their effects on heart metabolism of control-, LL- and HL-diet fed animals were evaluated. Substrate uptake, LDH release and adenine nucleotides, creatine phosphate, creatine, lactate, pyruvate, glucose-6-phosphate, glycogen, triglyceride and phospholipid content were determined in heart tissue.

Topics: Animals; Cardiomyopathies; Creatine Kinase; Dietary Fats; Energy Metabolism; Female; Glycogen; L-Lactate Dehydrogenase; Myocardium; Perfusion; Phosphocreatine; Pyruvates; Pyruvic Acid; Rats

It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings.

Topics: Adenosine Triphosphate; Allopurinol; Animals; Cardiomyopathies; Coronary Circulation; Creatine Kinase; Glycogen; L-Lactate Dehydrogenase; Myocardium; Norepinephrine; Oxygen Consumption; Rabbits

A 30 year old man with DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) syndrome associated with myocardial disease is reported. Echocardiographic study revealed a marked symmetric left ventricular hypertrophy. Histology of the endomyocardial biopsy specimen from the right ventricle showed severe glycogen deposition in the myocytes. This case may indicate that DIDMOAD syndrome is a hereditary systemic disease affecting multiple organs, including the myocardium.

Topics: Adult; Cardiomyopathies; Deafness; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Endocardium; Glycogen; Humans; Male; Myocardium; Optic Atrophy; Syndrome

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

Topics: Cardiomyopathies; Female; Glycogen; Humans; Infant; Kidney; Liver; Muscles; Myocardium; Phosphorylase Kinase

Ultrastructural alterations were studied in spontaneous round heart and furazolidone (FZ)-induced cardiomyopathy in turkey poults 20 to 31 days after hatching. The two most consistent morphological changes were abnormal accumulation of cytoplasmic glycogen and myofibrillar lysis. These alterations were more extensive in the drug-induced condition, which suggests that more myocytes are affected than in the spontaneous form of the disease. Data indicate that the myocyte contractile proteins sustain the major injury while other organelles appear to be involved only in an incidental manner. These findings corroborate previous suppositions which pointed toward a metabolic defect as the basic mechanism underlying the development of both spontaneous round heart and FZ-induced cardiomyopathy in turkey poults.

Topics: Age Factors; Animals; Cardiomyopathies; Furazolidone; Glycogen; Lipid Metabolism; Lysosomes; Microscopy, Electron; Mitochondria, Heart; Myocardium; Myofibrils; Poultry Diseases; Sarcoplasmic Reticulum

The case of a male infant with marked deposition of glycogen, confined to the heart, is presented. Clinically, prominent cardiomegaly had been evident from immediately after birth until the infant's death due to heart failure. There were no significant clinical manifestations in other organs, including liver and skeletal muscle, during the clinical course. Autopsy revealed abnormal deposition of normally structured glycogen in the heart, but no deposition in the liver, skeletal muscle, or other systemic organs. This unusual pattern of glycogen deposition was also confirmed by measurement of the glycogen content of each organ. This is the first report of glycogen storage disease confined to the heart. Enzymatic analysis revealed no decrease in the activities of acid maltase, amylo-1,6-glucosidase, and phosphorylase in the heart or in the liver or skeletal muscle. However, phosphorylase kinase activity was not detectable in the heart, although high activity levels were observed in the liver and skeletal muscle. In this case the inborn error of metabolism responsible for the isolated deposition of glycogen in heart muscle may have been due to a deficiency of cardiac phosphorylase kinase.

Topics: Cardiomyopathies; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease; Humans; Infant, Newborn; Liver; Liver Glycogen; Male; Muscles; Myocardium; Phosphorylase Kinase; Phosphorylases

Topics: Adenosine Triphosphate; Animals; Cardiomyopathies; Female; Glycogen; Isoproterenol; L-Lactate Dehydrogenase; Lactates; Lactic Acid; Male; Myocardium; Perhexiline; Phosphocreatine; Rats

Catecholamines have been shown to produce irreversible contraction band lesions of myocardial cells. However, little is known about the temporal appearance and correlation of the acute form of coagulative myocytolysis with ECG, hemodynamic and biochemical parameters. Groups of adult mongrel dogs were anesthetized with sodium pentobarbital, infused continuously with isoproterenol (2.5 micrograms/kg/min) and killed after periods of 0, 5, 15, 30, or 60 min. There were two predominant myocardial patterns: 'paradiscal' and 'holocytic' contraction band lesions. Either type of lesion was non-existent or rare in the control hearts. The small 'paradiscal' contraction band lesions were present as early as 5 min of isoproterenol infusion, particularly in the inner myocardial layer. The large 'holocytic' contraction band lesions were present by 15 min, however, they were not produced in any significant numbers before 30 min. Both types of contraction band lesions continued to accumulate up to 60 min. ST segment depression was the predominant ECG change. This occurred as early as 5 min when heart rate, blood pressure and dP/dt values had also significantly changed. The high-energy phosphates, phosphocreatine and ATP, started declining as early as 5 min. Furthermore, these phosphates and lactate were distributed in transmural gradients across the left ventricular wall with the greatest change in the endocardial third. This was also the site of the largest accumulation of each type of contraction band lesion. While the lesions correlated with certain biochemical and hemodynamic changes, the underlying pathophysiology is more complex than ischemia or high-energy phosphate depletion alone.

Topics: Adenosine Triphosphate; Animals; Cardiomyopathies; Dogs; Electrocardiography; Female; Glycogen; Hemodynamics; Isoproterenol; Male; Phosphocreatine; Time Factors

Glycogen aggregates in the cardiac muscle cell, which have been frequently demonstrated in endomyocardial biopsies under the transmission electron microscope, were studied using the optical microscope in order to clarify their histopathological significance in various heart diseases. The right ventricular muscle biopsies were obtained from the following 120 patients: 24 cases of congestive cardiomyopathy, 26 of hypertrophic cardiomyopathy, 28 of atrial septal defect, 6 of primary pulmonary hypertension, 31 of bradyarrhythmic hearts and 5 controls. The tissue specimens were fixed with glutaraldehyde and osmium tetraoxide, and embedded in epoxy resin. Semi-thin sections from these specimens were dyed with tribasic staining originated by KUROTAKI (1972). Under the optical microscope, glycogen is clearly identified by its forming red stained areas which are seen not only in the subsarcolemmal layers and the perinuclear region, but also in the intermyofibrillar zones. The glycogen aggregates are more frequently observed in the specimens from the atrial septal defects and the bradyarrhythmic hearts than in the other cases. Thus, observation of glycogen aggregates reveals notable differences in appearance depending on the kinds of diseases. In the bradyarrhythmic hearts, the glycogen aggregates can be more readily observed in specimens from younger patients than in elderly ones. Furthermore, the glycogen aggregates appear regardless of both the grades of hypertrophy and degeneration in myocardial cells. These results do not agree with previous reports that the occurrence of glycogen is proportional with the grade of cardiac cell hypertrophy and/or damage.

Topics: Adult; Aged; Bradycardia; Cardiomyopathies; Endocardium; Female; Glycogen; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitochondria, Heart; Muscles; Myofibrils

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.

Topics: Adenosine Triphosphatases; Animals; Calcium; Cardiomyopathies; Cold Temperature; Dogs; Female; Glycogen; Heart Arrest, Induced; Magnesium; Male; Myocardium; Myofibrils; Sarcoplasmic Reticulum

The case history, skeletal muscle and heart muscle biopsy findings from an affected member of a family suffering from hypokalaemic periodic paralysis associated with permanent muscular weakness are reported. The patient, a female aged 35 years, while treated with 750 mg and later 1000 mg of acetazolamide daily, developed typical exercise angina pectoris. The ECG during exercise showed ST-segment depression. A coronary angiography was performed because coronary artery disease was suspected. To exclude cardiac muscle disease a biopsy of the left ventricular wall was taken. The angiography was normal. Ultrastructural analysis of the biopsy specimen showed an unusual amount of intermyofibrillary glycogen resembling, although far less abundant, the increase of glycogen found in the skeletal muscle biopsy specimen obtained from the same patient. The possible implications of these findings are discussed with reference to the normal echocardiographic findings in the family.

Topics: Cardiomyopathies; Female; Glycogen; Histocytochemistry; Humans; Hypokalemia; Muscles; Myocardium; Paralyses, Familial Periodic

In severely phosphorous depleted rats, no change of glycogen content or activities of enzymes catalysing glycogen synthesis or breakdown was observed. In contrast in heart muscle, a decrease of myocardial glycogen content was observed which was accompanied by increased activity of phosphorylase and decreased activity of synthetase. It is assumed that these changes result from increased catecholamine action secondary to an activation of the sympathetic nerve system resulting from impaired contractile state of the myocardium. The changes observed are analogous to those found in heart failure.

Topics: Animals; Cardiomyopathies; Glycogen; Glycogen Synthase; Male; Phosphorus; Phosphorylases; Rats

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults two weeks posthatching to induce experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From ECG data obtained at weekly intervals, poults were selected for sacrifice at 3, 4, and 5 weeks of age. Myocardial samples from the right and left ventricular free walls were analyzed for glycogen by biochemical assay technics. Levels of glycogen were significantly (p less than .01) elevated in the FZ-treated poults at 3, 4, and 5 weeks of age. At all ages, the increase occurred in both the acid-soluble (TCA) and acid-insoluble (KOH) fractions with a proportionately greater increase in the TCA fraction. Results suggest that the effect of FZ on myocardial glycogen metabolism occurs very early and is more pronounced in the right ventricle than in the left ventricle even though both chambers may exhibit similar gross changes.

Topics: Animals; Cardiomyopathies; Furazolidone; Glycogen; Myocardium; Poultry Diseases; Turkeys

Unusual histological and ultrastructural changes in cardiac muscle cells have been found in 3 brothers with progressive myocardial deficiency. Histologically, this cardiomyopathy was characterized by massive storage of PAS-negative proteinaceous material in most cardiac muscle cells. The electron microscope showed that this material consisted of sinuous filaments, 7-10 nm in diameter, similar to the intermediate filaments normally present in cardiac muscle cells. Filament storage coincided with the disintegration of neighbouring myofibrils, with particular change in Z bands giving rise to rod-like bodies and more complex structures formed by the association of Z band material and sarcoplasmic reticulum (SR) tubules. Filament storage and myofibrillar disintegration always occurred in areas where the SR developed and involuted extensively. Relatively high glycogen accumulation also occurred, in close relation to the SR changes. Discrete SR proliferation, glycogen overload and filament deposits were observed in a few skeletal fibres. These observations suggest that disturbance in the metabolism of desmin (protein subunit of intermediate filaments and a fundamental component of Z bands) might be involved in this type of cardiomyopathy. The influence of a chronic defect in calcium regulation might also be envisaged in view of the marked SR abnormalities.

Topics: Adult; Cardiomyopathies; Glycogen; Humans; Male; Microscopy, Electron; Myocardium; Myofibrils; Sarcoplasmic Reticulum

Changes in the myocardium developing after a single injection of toxic doses of adrenaline were studied. The course of adrenaline damage of the myocardium was shown to be wave-like. The most massive areas of degeneration and necrosis were observed on the 7th--14th day of the experiment. Ischemia developing because of the change of the microcirculation bed and impaired hemodynamics in the myocardium is a very important factor in the pathogenesis of adrenaline damage. The development of degeneration and necrotic areas in the auricles was found to occur later than in the ventricles which may be due to the ultrastructural features of atrial cardiomyocytes: the presence of electron dense granules, the destruction and decrease in the number of which coincide with the most marked signs of the heart muscle injury.

Topics: Animals; Cardiomyopathies; Epinephrine; Glycogen; Heart Atria; Heart Ventricles; Histocytochemistry; L-Lactate Dehydrogenase; Myocardium; Rabbits; Ribonucleoproteins; Succinate Dehydrogenase; Time Factors

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

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults 2--5 weeks after hatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at weekly intervals, poults were selected for sacrifice at 5 and 10 weeks of age. Poults were sacrificed by cervical dislocation and appropriate samples of tissue from the left ventricle, liver, pectoralis and tibialis cranialis muscles were removed for glycogen assays. Character of glycogen, as determined by percent of branching and number of glucose units per segment, was not significantly altered in poults with spontaneous round heart disease or FZ-induced cardiomyopathy. This suggests that the glycogen accumulation noted in these conditions most closely resembles type II glycogenosis.

Topics: Animals; Cardiomyopathies; Furazolidone; Glucose; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Heart Diseases; Liver; Liver Glycogen; Muscles; Myocardium; Pectoralis Muscles; Poultry Diseases; Turkeys

Topics: Atrioventricular Node; Bundle of His; Cardiomyopathies; Consanguinity; Electrocardiography; Female; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Infant; Muscles; Myocardium; Wolff-Parkinson-White Syndrome

Endomyocardial tissue obtained from 237 patients clinically suspected of suffering from congestive cardiomyopathy, has been analysed histologically, histochemically and ultrastructurally. In 51% of patients, the suspected diagnosis was morphologically confirmed and in 24.5%, no pathological evidence of a dilated heart or other pathology was found. The results in these two groups were considered helpful. It is concluded that, even though the morphology of congestive cardiomyopathy in non-specific and the number of other pathology found is small, the continuation of investigation by bioptome is justified. Parameters such as prognosis and length of history can also be assessed. Furthermore, morphological analysis is essential to interpret accurately biochemical and other types of investigations that are being carried out on biopsy material.

Topics: Adolescent; Adult; Aged; Cardiomyopathies; Child; Female; Glycogen; Histocytochemistry; Humans; Male; Microscopy, Electron; Middle Aged; Myocardium; Succinate Dehydrogenase

Topics: Acetate-CoA Ligase; Alcohol Oxidoreductases; Alcoholism; Aldehyde Oxidoreductases; Animals; Cardiomyopathies; Cholesterol; Creatine Kinase; Diet; Disease Models, Animal; Ethanol; Glycogen; Humans; L-Lactate Dehydrogenase; Lipid Metabolism; Male; Mice; Mitochondria, Muscle; Myocardium; Triglycerides

Transvenous right ventricular endomyocardial biopsy in an 11-yr-old boy with a proximal skeletal myopathy and a cardiomyopathy, has shown a major increase in mitochondrial size and numbers on electron-microscopic morphometry, with formation of unique ring-shaped mitochondria in cardiac muscle cells. The significance of this finding and the use of cardiac biopsy in children are discussed.

Topics: Cardiomyopathies; Child; Glycogen; Humans; Male; Microtubules; Mitochondria, Muscle; Muscular Diseases; Myocardium; Myofibrils

The investigation included a study of the content of glycogen, of the activity of the enzymes of its decay (phosphorylase and hydrolytic enzymes), of the content of lactic acid, and glucose in rats following the administration of myocardium damaging doses of adrenalin, as well as in animals who had died after the administration of adrenalin or were agonizing. The analysis of the carbohydrate metabolism parameters in animals who had died due to the adrenalin administration, or who had been sacrificed in an agonizing state (sharp fall of the glycogen content in the heart, increased activity of hydrolytic enzymes in the heart during the agonizing phase) indicated that the temporary elevation of the glycogen content in the heart after the administration of 300microng/100g of adrenalin was a compensatory reaction of the body. It is suggested that a certain relationship exists between the markedness of this compensatory reaction, i.e. the glycogen level in the heart muscle, and the severity of necrotic lesions.

Topics: Amylases; Animals; Blood Glucose; Carbohydrate Metabolism; Cardiomyopathies; Epinephrine; Female; Glycogen; Lactates; Muscles; Myocardium; Phosphorylases; Rats

Clinical and pathologic findings are presented in 14 patients (six newly reported, eight described previously), all children ranging in age from 6 to 24 months, with a clinicopathologic syndrome termed "infantile cardiomyopathy with histiocytoid change in cardiac muscle cells." This syndrome is manifested clinically by severe, eventually fatal cardiac arrhythmias, and is characterized pathologically by cardiac hypertrophy and by a distinctive type of focal degeneration of the muscle cells, which lose their myofibrils, undergo marked mitochondrial hyperplasia, become rounded in shape and enlarged, and resemble histiocytes. Evidence is presented to support the conclusions that these manifestations are those of a cardiomyopathy, that cardiac hypertrophy precedes the onset of the clinical features, that the focal degeneration is likely to be a cause rather than a consequence of the arrhythmias, and that the latter develop only in the late stages of the disorder. The etiology of this cardiomyopathy remains unclear.

Topics: Cardiomyopathies; Cell Nucleus; Child, Preschool; Cytoplasmic Granules; Endocardium; Female; Glycogen; Histiocytes; Humans; Infant; Male; Mitochondria, Muscle; Myocardium; Myofibrils; Ribosomes; Vacuoles

Although the effect of cold and heat stress on myocardial metabolisms has been widely studied, this parameter has not been investigated over a wide range of environmental temperatures after myocardial infarction. Since high as well as low temperatures are known to adversely affect the myocardium, changes in enviromental temperature are likely to be of great importance to patients suffering from acute coronary insult. Therefore, the myocardial metabolism was studied at different environmental temperatures in albino rats with isoproterenol-induced infarct-like myocardial necrosis. Male albino rats weighing 100 to 150 g were selected for the study. The investigations included ECG (lead II), histology, serum free fatty acids (FFA), serum triglycerides (TGS), cardiac noradrenaline, cardiac glycogen, and adrenal ascorbic acid, after the induction of myocardial necrosis. The biochemical changes were minimum between 10 and 15 degrees C while, at 4 degrees C, marked changes were observed. No significant change was seen in the serum triglycerides.

Topics: Adrenal Glands; Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Cardiomyopathies; Fatty Acids, Nonesterified; Glycogen; Heart; Isoproterenol; Male; Myocardial Infarction; Myocardium; Necrosis; Norepinephrine; Organ Size; Rats; Temperature

The possibility of prevention of isoproterenol (ISO)-induced morphological changes by Ca2+ antagonists was investigated in the heart muscle of dogs. ISO in a dose of 7 mg/kg caused marked histochemical and electron microscopical necrotic changes. K+, Mg2+ aspartate (K,Mg-ASP) administered alone in a dose of 100 mg/kg changed slightly almost all cell components. K,Mg-ASP treatment applied prior to administration of ISO after 24 hours resulted in an improvement of the ultrastructure, which generally exhibited marked restoration resembling metabolic regeneration and/or enhanced metabolic activity.

Topics: Animals; Aspartic Acid; Calcium; Cardiomyopathies; Dogs; Glycogen; Isoproterenol; Magnesium; Male; Myocardium; Oxidoreductases; Potassium; Time Factors

Vesicular myocardial change is a specific and common finding in the diseased hearts of humans and experimental animals. The small to large vesicles are generally bound by a double membrane. They are formed within myocardial cells and then possibly extruded into the extracellular space where they disintegrate or are phagocytosed by mononuclear cells. On the basis of our studies, most vesicles appear to be of mitochonrial origin. In humans, vesicular myocardial change appears to be most extreme in primary cardiomyopathy. It may also be present, but in lesser degree, in the apparently normal hearts of human adults. Vesicular myocardial change probably represents a specific mechanism by which myocardial cells eliminate damage mitochondria or other undesirable elements that build within them as a result of disease, aging, and perhaps normal physiological activity.

Topics: Adolescent; Adult; Animals; Cardiomyopathies; Extracellular Space; Female; Glycogen; Heart Diseases; Humans; Male; Membranes; Middle Aged; Mitochondria, Muscle; Myocardium; Myofibrils; Phagocytosis; Sarcolemma

Topics: Biopsy; Body Weight; Cardiomyopathies; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infant, Newborn; Liver; Muscles; Muscular Diseases; Prenatal Diagnosis; Skin

Topics: Animals; Cardiomyopathies; Catecholamines; Electron Transport Complex IV; Esterases; Glycogen; Heart; Lipid Metabolism; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Necrosis; Oxidoreductases; Sarcoplasmic Reticulum; Stress, Physiological; Swine

Topics: Adolescent; Biopsy; Cardiomyopathies; Diagnosis, Differential; Electromyography; Glucosidases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Male; Microscopy, Electron; Muscles; Muscular Dystrophies; Myofibrils; Syndrome

Topics: Abortion, Therapeutic; Adult; Amniocentesis; Amnion; Cardiomyopathies; Cells, Cultured; Clinical Enzyme Tests; Consanguinity; Female; Fetus; Germany, West; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infant Mortality; Infant, Newborn; Lysosomes; Male; Microscopy, Electron; Muscle Tonus; Muscles; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Syndrome

Topics: Adult; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biopsy; Cardiomyopathies; Cell Membrane; Cytoplasmic Granules; Desmosomes; Endocardium; Endoplasmic Reticulum; Female; Glycogen; Golgi Apparatus; Heart Valve Diseases; Heart Ventricles; Humans; Male; Microscopy, Electron; Mitochondria; Mitral Valve Insufficiency; Myocardium; Myofibrils; Sarcoplasmic Reticulum; Temperature

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: Animals; Cardiomyopathies; Cobalt; Creatine Kinase; Electrocardiography; Electron Transport Complex IV; Fatty Acids, Nonesterified; Glycogen; Humans; Hydroxybutyrate Dehydrogenase; Male; Myocardium; Phospholipids; Rats; Succinate Dehydrogenase; Time Factors

Topics: Alcoholic Intoxication; Animals; Blood Glucose; Cardiomyopathies; Disease Models, Animal; Ethanol; Fatty Acids, Nonesterified; Glycogen; Humans; Injections, Intraperitoneal; Lactates; Mitochondria; Myocardium; Statistics as Topic

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: Animals; Cardiomyopathies; Cell Membrane; Cell Nucleolus; Cell Nucleus; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Lipids; Lysosomes; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Organoids; Rabbits; Rats

Topics: Acid Phosphatase; Beer; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Cobalt; Glycogen; Histocytochemistry; Humans; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Succinate Dehydrogenase

Topics: Adult; Biopsy; Blood Pressure; Cardiac Catheterization; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Edema; Female; Glycogen; Humans; Male; Microscopy; Microscopy, Electron; Microtubules; Middle Aged; Mitochondria; Myocardium; Sarcoplasmic Reticulum

Topics: Animals; Cardiomyopathies; Collagen; Glycogen; Glycolysis; Hydroxyproline; Male; Myocardium; Necrosis; Norepinephrine; Phosphorus; Proline; Rabbits

Topics: Alcoholism; Autopsy; Biopsy; Cardiomyopathies; Cytoplasm; Glycogen; Humans; Lipids; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Myofibrils

Topics: Actins; Adult; Animals; Biopsy; Cardiomyopathies; Cell Nucleus; Dogs; Glycogen; Golgi Apparatus; Heart Atria; Heart Ventricles; Histocytochemistry; Humans; Lipids; Lysosomes; Male; Microscopy, Electron; Mitochondria, Muscle; Mitral Valve Stenosis; Myocardium; Myofibrils; Myosins; Ribosomes; Sarcolemma; Sarcoplasmic Reticulum

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: Adolescent; Adult; Age Factors; Aged; Cardiomyopathies; Child; Child, Preschool; Cytoplasm; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Hypothyroidism; Infant; Infant, Newborn; Microscopy, Electron; Middle Aged; Myocardium; Myoclonus; Polysaccharides; Staining and Labeling

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: Animals; Cardiomyopathies; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Endoplasmic Reticulum; Epinephrine; Glycogen; Heart; Histocytochemistry; Lipids; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardial Infarction; Myocardium; Myofibrils; NAD; NADP; Necrosis; Rats; Succinate Dehydrogenase; Transferases

Topics: Autopsy; Biopsy; Cardiomyopathies; Glucosidases; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Humans; Infant; Kidney; Kidney Diseases; Liver; Liver Diseases; Microscopy, Electron; Muscles; Muscular Diseases; Myocardium; Ultracentrifugation

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: Animals; Cardiomyopathies; Disease Models, Animal; Epinephrine; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Heart; Myocardium; Rats

Topics: Animals; Calcinosis; Cardiomyopathies; Disease Models, Animal; Endoplasmic Reticulum; Female; Glycogen; Histocytochemistry; L-Lactate Dehydrogenase; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Necrosis; Nephrectomy; Parathyroid Glands; Rats; Succinate Dehydrogenase; Transferases; Uremia

Topics: Adult; Autopsy; Cardiac Catheterization; Cardiomyopathies; Cell Nucleus; Cytoplasm; Electrocardiography; Female; Glycogen; Histocytochemistry; Humans; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Pregnancy; Puerperal Disorders

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

Topics: Alkaline Phosphatase; Animals; Calcium; Cardiomyopathies; Digitoxin; Electron Transport Complex IV; Female; Glucosyltransferases; Glycogen; Histocytochemistry; Hypoxia; Lipid Metabolism; Necrosis; Oils; Papillary Muscles; Phosphates; Rats; Succinate Dehydrogenase; Water-Electrolyte Balance

Topics: Adult; Cardiac Catheterization; Cardiomyopathies; Electrocardiography; Fatty Acids, Nonesterified; Female; Galactose; Glycogen; Glycogen Storage Disease; Humans; Lactates; Liver Glycogen; Male; Middle Aged; Muscles; Myocardium; Oxygen Consumption; Pedigree; Pyruvates; Radiography

Topics: Animals; Cardiomyopathies; Glycogen; Hyperthyroidism; Magnesium; Methionine; Myocardium; Phosphocreatine; Rabbits

Topics: Carbohydrate Metabolism; Cardiomyopathies; Glycogen; Glycogen Storage Disease; Glycosaminoglycans; Histocytochemistry; Humans; Infant; Male; Muscles

Topics: Cardiomyopathies; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Myocardium; Succinate Dehydrogenase; Tuberculosis, Pulmonary

Topics: Cardiomyopathies; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Histocytochemistry; Humans; In Vitro Techniques; Skin

Topics: Animals; Cardiomyopathies; Cattle; Coffee; Edema; Glycogen; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Myofibrils

Topics: Cardiomyopathies; Diagnosis, Differential; Glycogen; Heart Diseases; Histocytochemistry; Humans; Monoamine Oxidase; Myocardium; Pathology; Phosphorylases; Phosphotransferases; Rats; Research

Topics: Cardiomyopathies; Disease; Glycogen; Glycogen Storage Disease; Heart Diseases; Heart Ventricles; Humans; Myocardium