glycogen and Arrhythmias--Cardiac

Acclimatisation to environmental hypoxia initiates a series of metabolic and musculocardio-respiratory adaptations that influence oxygen transport and utilisation, or better still, being born and raised at altitude, is necessary to achieve optimal physical performance at altitude, scientific evidence to support the potentiating effects after return to sea level is at present equivocal. Despite this, elite athletes continue to spend considerable time and resources training at altitude, misled by subjective coaching opinion and the inconclusive findings of a large number of uncontrolled studies. Scientific investigation has focused on the optimisation of the theoretically beneficial aspects of altitude acclimatisation, which include increases in blood haemoglobin concentration, elevated buffering capacity, and improvements in the structural and biochemical properties of skeletal muscle. However, not all aspects of altitude acclimatisation are beneficial; cardiac output and blood flow to skeletal muscles decrease, and preliminary evidence has shown that hypoxia in itself is responsible for a depression of immune function and increased tissue damage mediated by oxidative stress. Future research needs to focus on these less beneficial aspects of altitude training, the implications of which pose a threat to both the fitness and the health of the elite competitor. Paul Bert was the first investigator to show that acclimatisation to a chronically reduced inspiratory partial pressure of oxygen (P1O2) invoked a series of central and peripheral adaptations that served to maintain adequate tissue oxygenation in healthy skeletal muscle, physiological adaptations that have been subsequently implicated in the improvement in exercise performance during altitude acclimatisation. However, it was not until half a century later that scientists suggested that the additive stimulus of environmental hypoxia could potentially compound the normal physiological adaptations to endurance training and accelerate performance improvements after return to sea level. This has stimulated an exponential increase in scientific research, and, since 1984, 22 major reviews have summarised the physiological implications of altitude training for both aerobic and anaerobic performance at altitude and after return to sea level. Of these reviews, only eight have specifically focused on physical performance changes after return to sea level, the most comprehensive of which was recently written by Wo

Topics: Acclimatization; Altitude; Altitude Sickness; Anaerobic Threshold; Arrhythmias, Cardiac; Buffers; Cardiac Output; Environment; Glycogen; Health Status; Heart; Hematopoiesis; Hemoglobins; Hemolysis; Humans; Hypoxia, Brain; Immune Tolerance; Muscle, Skeletal; Oxidative Stress; Oxygen; Oxygen Consumption; Partial Pressure; Physical Education and Training; Physical Endurance; Physical Fitness; Plasma Volume; Pulmonary Edema; Regional Blood Flow; Respiration; Respiratory Muscles; Sports; Work of Breathing

Topics: Arrhythmias, Cardiac; Glucose; Glycogen; Glycolysis; Heart; Humans; Insulin; Muscles; Myocardial Infarction; Myocardium; Pentoses; Potassium

Acute myocardial infarction is viewed as a severe trauma causing a generalized metabolic reaction; an acute emotional stress with further metabolic implications; and a localized wound in which there is an acute increase in carbohydrate metabolism, followed by protein synthetic reactions leading to scar formation. The metabolic response is vital to the patient's successful adaptation to his myocardial infarction.

Topics: Adenosine Triphosphate; Adrenocorticotropic Hormone; Animals; Arrhythmias, Cardiac; Catecholamines; Cicatrix; Fatty Acids, Nonesterified; Glucose; Glycogen; Growth Hormone; Humans; Hydrocortisone; Hypoxia; Insulin; Insulin Secretion; Myocardial Infarction; Potassium; Stress, Physiological; Stress, Psychological

Myocardial preservation was assessed in 72 patients undergoing extensive myocardial revascularization. The patients were allocated at random to three surgical techniques: Group 1, intermittent aortic cross-clamping at 32 degrees C; Group 2, intermittent aortic cross-clamping at 25 degrees C; and Group 3, St. Thomas' Hospital cardioplegia. As intraoperative markers of ischemic damage, adenosine triphosphate, creatine phosphate, and glycogen contents were determined in transmural left ventricular biopsy specimens taken at the beginning and at the end of cardiopulmonary bypass. Ultrastructure was studied in a similar pair of biopsy specimens. Release of myocardium-specific creatine kinase isoenzyme was determined intraoperatively and postoperatively. Functional recovery was assessed before and after weaning from cardiopulmonary bypass. The incidence of low cardiac output, myocardial infarction, and rhythm disturbances was compared between groups. Finally, actuarial survival and event-free curves were studied after 18 months' follow-up. The results show a better preservation of high-energy phosphates, glycogen, and ultrastructure in the cardioplegia group as compared to the two cross-clamp groups. However, severe myocardial damage was never observed. Release of MB creatine kinase isoenzyme was the same in all three groups. Functional recovery of the hearts immediately after cessation of cardiopulmonary bypass was better in the cardioplegia group, but the incidence of rhythm disturbances (atrioventricular conduction problems) was higher in the cardioplegia group than in the other two groups (p less than 0.05). Clinical outcome in terms of incidence of perioperative infarction, survival, and event-free follow-up was not different between groups. It is concluded that both techniques (aortic cross-clamping at 32 degrees C or 25 degrees C and St. Thomas' Hospital cardioplegia) offer good myocardial protection in extensive aorta-coronary bypass operations. St. Thomas' cardioplegia, however, in contrast to intermittent aortic cross-clamping, prevents the onset of ischemia-induced deterioration of cardiac metabolism, i.e., destruction of the adenine nucleotide pool.

Topics: Adenosine Triphosphate; Adult; Aorta; Arrhythmias, Cardiac; Cardiac Output; Cardiac Output, Low; Cardiopulmonary Bypass; Clinical Trials as Topic; Constriction; Coronary Artery Bypass; Creatine Kinase; Follow-Up Studies; Glycogen; Heart Arrest, Induced; Hemodynamics; Humans; Intraoperative Complications; Isoenzymes; Myocardial Infarction; Myocardium; Phosphocreatine; Random Allocation

To elucidate the complex impact of hypoxia on adipose tissue, resulting in biased metabolism, insulin resistance and finally diabetes we used mature adipocytes derived from a Simpson-Golabi-Behmel syndrome patient for microarray analysis. We found a significantly increased transcription rate of genes involved in glycolysis and a striking association between the pattern of upregulated genes and disease biomarkers for diabetes mellitus and insulin resistance. Although their upregulation turned out to be HIF-1α-dependent, we identified further transcription factors mainly AP-1 components to play also an important role in hypoxia response. Analyzing the regulatory network of mentioned transcription factors and glycolysis targets we revealed a clear hint for directing glycolysis to glutathione and glycogen synthesis. This metabolic switch in adipocytes enables the cell to prevent oxidative damage in the short term but might induce lipogenesis and establish systemic metabolic disorders in the long run.

Topics: Adipocytes; Adipogenesis; Arrhythmias, Cardiac; Biomarkers; Cell Hypoxia; Gene Expression Profiling; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Glutathione; Glycogen; Glycolysis; Heart Defects, Congenital; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin Resistance; Intellectual Disability; Oligonucleotide Array Sequence Analysis; Protein Interaction Mapping; Signal Transduction; Transcription Factor AP-1; Transcription, Genetic

Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

Topics: Animals; Arrhythmias, Cardiac; Coronary Vessels; Energy Metabolism; Glycogen; Lactic Acid; Ligation; Male; Myocardial Ischemia; Phosphocreatine; Rats; Rats, Wistar; Uridine; Uridine Monophosphate

Glycogen, which serves as a major energy reserve in cells, is a large, branched polymer of glucose molecules. We describe a patient who had muscle weakness, associated with the depletion of glycogen in skeletal muscle, and cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart. The skeletal muscle showed a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation. Western blotting showed the presence of unglucosylated glycogenin-1 in the muscle and heart. Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other. The missense mutation resulted in inactivation of the autoglucosylation of glycogenin-1 that is necessary for the priming of glycogen synthesis in muscle.

Topics: Adult; Arrhythmias, Cardiac; Codon, Nonsense; Dizziness; DNA, Complementary; Female; Glucosyltransferases; Glycogen; Glycoproteins; Humans; Male; Muscle, Skeletal; Mutation, Missense; Pedigree; RNA, Messenger; Sequence Analysis, DNA

The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation. Mutations in the gamma2 and gamma3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart and elevated glycogen in pig muscle, respectively. A putative glycogen binding domain (GBD) has now been identified in the beta subunits. Coexpression of truncated beta subunits lacking the GBD with alpha and gamma subunits yielded complexes that were active and normally regulated. However, coexpression of alpha and gamma with full-length beta caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated beta subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with gamma2 mutations.

Topics: AMP-Activated Protein Kinases; Arrhythmias, Cardiac; Cell Line, Tumor; Glycogen; Glycogen Synthase; Humans; Inclusion Bodies; Multienzyme Complexes; Precipitin Tests; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Subunits; Recombinant Fusion Proteins; Sequence Deletion

Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i.v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectively suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additional protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. Preconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention did not cause any further reduction in the level of lactate. In conclusion, diabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolytic metabolites during ischemia can account for the enhanced resistance of diabetic hearts to ischemia as well as for the lack of further protection by preconditioning.

Topics: Animals; Arrhythmias, Cardiac; Blood Glucose; Diabetes Mellitus, Experimental; Glycogen; Heart; Heart Rate; In Vitro Techniques; Ischemic Preconditioning, Myocardial; Lactic Acid; Male; Myocardial Ischemia; Myocardium; Rats; Rats, Wistar

The effects of iloprost infusion (100 ng/kg/min for 75 min) alone and in combination with aspirin (3 mg/kg IV bolus) were compared in a canine model of myocardial reperfusion injury. Regional ischemia of 40 min was produced by temporary occlusion of the left anterior descending coronary artery, after which the myocardium was reperfused for a period of 3 hours. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LVdP/dtmax and negative (-) LVdP/dtmax were monitored. Rate pressure product and (-) dP/dt/Pmax were also derived from the above. Myocardial tissue levels of adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate were estimated. Following reperfusion in the saline treated group, there was a significant fall in (i) MAP, (ii) (+) LVdP/dtmax and (iii) (-) LVdP/dtmax. LVEDP was corrected about 2 hours after reperfusion. Despite correction of lactate accumulation, ATP and glycogen were not restored although the CP store was replenished. The hemodynamic profiles in both iloprost and in combination treated groups were similar; (i) depressed MAP (particularly during iloprost infusion) without any significant change in HR (ii) no significant depression in (+) LVdP/dtmax (iii) depression in (-) LVdP/dtmax but not when corrected for lower Pmax and (iv) a significant reduction in the incidence of reperfusion arrhythmias. Similarly, in both the drug/s treated groups, ATP, CP and lactate were normalised although glycogen store was not restored. The results of this study indicate (i) cardioprotective effect of iloprost even when administered prior to reperfusion and (ii) no additional protective effect of combining iloprost and aspirin.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Aspirin; Blood Pressure; Cyclooxygenase Inhibitors; Disease Models, Animal; Dogs; Drug Synergism; Drug Therapy, Combination; Glycogen; Heart Rate; Iloprost; Lactic Acid; Myocardial Reperfusion Injury; Myocardium; Phosphocreatine; Ventricular Pressure

The aim was to assess the abilities of exogenous noradrenaline, isoprenaline, and phenylephrine to precondition the isolated rat heart against ischaemic and reperfusion injury.. The isovolumetric Langendorff rat heart model was used to determine postischaemic recovery of left ventricular function. The hearts were subjected to 30 min of normothermic global ischaemia followed by 30 min reperfusion. Treated hearts were perfused with noradrenaline (10(-7) M), isoprenaline (10(-8) M), or phenylephrine (10(-6) M, 10(-5) M, and 10(-4) M) for 5 min followed by 5 min washout before the 30 min ischaemic period.. Control hearts recovered 47.6(SEM 4.3)% of baseline heart rate x developed pressure after 30 min reperfusion, whereas noradrenaline and isoprenaline treated hearts recovered 75.1(4.6) and 76.4(4.6)%, respectively (p < 0.001 v control). Left ventricular end diastolic pressures at the end of reperfusion were 48.8(4.0), 20.0(2.4), and 21.6(2.7)mm Hg for control, noradrenaline treated (p < 0.001 v control), and isoprenaline treated (p < 0.001 v control) hearts respectively. beta Blockade with propranolol during noradrenaline treatment blocked the protective effects. No concentration of phenylephrine used was able to enhance postischaemic heart rate x developed pressure significantly, or result in improved (lower) postischaemic left ventricular end diastolic pressure. During treatment with noradrenaline and phenylephrine (10(-5) M), lactate release was 13.0(1.0) and 11.0(0.9) mumol.5 min-1, respectively (p = NS); these values were significantly (p < 0.001) greater than baseline value of 3.7(0.5) mumol.5 min-1. Immediately before the 30 min ischaemic period, control and phenylephrine treated groups had glycogen levels of 132(14) and 128(5) nmol.mg-1 protein, respectively (p = NS), whereas the glycogen content of the noradrenaline treated group was only 96(5) nmol.mg-1 protein (p < 0.05 v control and phenylephrine treated).. Transient beta adrenergic but not alpha 1 adrenergic stimulation can precondition the isolated perfused rat heart. The mechanism of protection may, at least in part, be due to transient demand ischaemia. Partial depletion of glycogen following treatment may play a role in the observed protective effects.

Topics: Adrenergic beta-Agonists; Animals; Arrhythmias, Cardiac; Glycogen; Heart; Isoproterenol; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Norepinephrine; Perfusion; Phenylephrine; Rats; Rats, Sprague-Dawley; Stimulation, Chemical

The dietary polyunsaturated fatty acids are well known to promote the cardiac output and to protect the myocardium against arrhythmias. The exogenous glucose is generally considered as a protective agent against arrhythmias resulting from ischemia and reperfusion. But the effects of dietary fats, which also influence arrhythmias, on this beneficial effect of glucose has not been yet considered. We have studied the effects of a 7 days diet with or without polyunsaturated fatty acids on the cardiac performance and arrhythmias of isolated rat hearts, perfused with saline containing either glucose 5.5 mM or 11 mM. Acute regional ischemia was produced by ligature of the left main coronary artery with subsequent release to achieve reperfusion for some hearts. Previously, our results showed that the dietary polyunsaturated fatty acids led to an enhancement of the cardiac performance and to a decreased susceptibility to arrhythmias. The present data showed that the protective action of the exogenous glucose appeared to be dependent of the dietary lipid profile. Dietary polyunsaturated fatty acids increase cardiac performance under ischemia and decrease ventricular arrhythmias' occurrence under ischemia and on reperfusion. It might be related to endogenous substrate utilization and exogenous glucose availability which was influenced by the coronary flow.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Output; Coronary Circulation; Coronary Disease; Dietary Fats, Unsaturated; Glucose; Glycogen; Heart Rate; Male; Myocardium; Oxygen Consumption; Phospholipids; Rats; Rats, Inbred Strains; Reperfusion Injury; Triglycerides

We have examined the effects of bupivacaine and lignocaine on myocardial metabolism in the rat isolated heart-lung preparation. Bupivacaine 1, 5 or 25 micrograms ml-1 or lignocaine 4, 20 or 100 micrograms ml-1 was administered 5 min after the start of perfusion. Both bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 reduced heart rate significantly. Bupivacaine 25 micrograms ml-1 was associated with a higher incidence of arrhythmias than the other groups. Three hearts in the bupivacaine 25 micrograms ml-1 group (n = 8) and two hearts in the lignocaine 100 micrograms ml-1 group (n = 8) failed (zero cardiac output) at the end of the experiment. Although there were no significant differences in myocardial lactate and glycogen concentrations between groups, ATP content in the bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 groups was significantly less than that in the control group. The results suggest that myocardial depression and subsequent metabolic deterioration occurred with both the high doses of local anaesthetics; these findings do not account for the apparent increased cardiotoxicity of bupivacaine.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bupivacaine; Cardiac Output; Glycogen; Heart; Heart Rate; Lactates; Lactic Acid; Lidocaine; Lung; Male; Myocardium; Rats; Rats, Inbred WKY

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

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

The effect of myocardial catecholamine depletion on cellular electrophysiology and arrhythmias was assessed in Langendorff perfused guinea pig hearts during ischaemia and reperfusion. Myocardial noradrenaline was reduced to 0.17 +/- 0.04 microgram X g-1 by intracardiac injection of 6-hydroxydopamine (450 mg X kg-1 in six doses over 20 days) compared with 1.5 +/- 0.2 microgram X g-1 in vehicle injected controls. Myocardial catecholamine depletion significantly reduced the incidence of ventricular tachycardia and fibrillation during 30 min of global ischaemia and subsequent reperfusion. Myocardial catecholamine depletion prolonged action potential duration and refractory period during control perfusion and blunted ischaemia induced reduction in action potential amplitude, Vmax, and duration, but accentuated the prolongation in conduction time and QRS width. Catecholamine depletion abolished or attenuated reperfusion induced shortening of action potential duration and refractory period. Catecholamine depletion increased myocardial glycogen levels from 2.47 +/- 0.3 mg X g-1 wet weight to 4.39 +/- 0.3 mg X g-1; fasting animals for 48 h prior to study reversed this with no attenuation of the electrophysiological or antiarrhythmic action. These results provide further evidence that release of endogenous myocardial catecholamines contributes to the electrophysiological changes and arrhythmias associated with myocardial ischaemia and reperfusion.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Catecholamines; Coronary Disease; Glycogen; Guinea Pigs; Heart; Hydroxydopamines; In Vitro Techniques; Male; Myocardium; Norepinephrine; Oxidopamine; Perfusion; Tachycardia; Ventricular Fibrillation

Diuretic therapy is the most common cause of potassium deficiency. Although the extent of potassium deficiency usually does not exceed 200 or 300 mEq, under appropriate circumstances such modest deficiency may have important consequences. Factors that tend to increase the incidence or severity of potassium deficiency in patients who take diuretics include high salt diets, large urine volumes, metabolic alkalosis, increased aldosterone production, and the simultaneous use of two diuretics that act on different sites in the renal tubule. There are many serious complications of potassium deficiency, including cardiac arrhythmias, muscle weakness, rhabdomyolysis, glucose intolerance, and several complications that result directly from increased ammonia production, such as protein and nitrogen wasting and hepatic coma. Emphasized herein are those conditions that impose potential danger in patients with mild hypokalemia. Important factors that identify specific causes of potassium deficiency and its treatment are discussed briefly.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular System; Diuretics; Glycogen; Homeostasis; Humans; Hypokalemia; Muscle, Smooth; Muscles; Potassium Deficiency; Proteins

In attempts to determine the mechanism(s) underlying reflow rhythm disturbances, we have studied the relationship between extent of coronary flow impairment and incidence of reperfusion arrhythmias. In isolated guinea pig hearts perfused with pyruvate (10 mmol/l) and glucose (0.5 mmol/l), coronary flow was reduced to different extents (18, 11, 6, 1, and 0.5%). Following 10 minutes of ischemia, reflow arrhythmias were quantitated with computer-aided statistical determination of rate-independent variations in beat intervals. The results (19 +/- 1, 13 +/- 5, 22 +/- 4, 8 +/- 3 and 6 +/- 1, n = 6, Rhythm Disturbance Units respectively) revealed that rhythm disturbances were more serious after less severe ischemia than after more severe ischemia. To investigate this "paradoxical" observation, we compared the metabolic changes during ischemia and the severity of subsequent reflow arrhythmias. Electrical instability during reperfusion was not related to accumulation of lactate, increase in cyclic AMP or decline in energy status. These were at a maximum in the severely ischemic myocardium. The reduced incidence of arrhythmias following severe (1% and 0.5% flow) as opposed to moderate ischemia, however, may have been associated with a major increase in glycogenolysis (from 1.2 to 7.4 and 7.6 mumol glucose equivalents/min per g dry weight).

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Coronary Disease; Cyclic AMP; Glucose; Glycogen; Glycolysis; Guinea Pigs; Lactates; Lactic Acid; Male; Myocardium; Perfusion; Potassium; Pyruvates

Two cases of ophthalmoplegia-plus are described for the first time in the national literature. The clinical picture of both patients aged 7 and 15 years exhibited a characteristic triad: external ophthalmoplegia, retinitis pigmentosa and heart conduction impairments. In one patient, this triad was supplemented by neurosensory deafness, torsion dystonia and the myopathic syndrome, and in the other one, by ichthyosis, cerebellar symptomatology, the myopathic syndrome and a marked elevation of protein in the cerebrospinal fluid. In both patients, the diagnosis was supported by electron microscopic studies of a muscular biopsy-specimen which disclosed pronounced changes in the number, structure, size and form of mitochondria as well as the presence of glycogen and lipid drops accumulating near mitochondria.

Topics: Abetalipoproteinemia; Adolescent; Arrhythmias, Cardiac; Child; Female; Glycogen; Humans; Lipid Metabolism; Mitochondria, Muscle; Muscles; Ophthalmoplegia; Retinitis Pigmentosa; Syndrome

The experiments on anaesthetized dogs have shown that with artificial ventilation and open chest adrenalin in arrhythmogenic and nonarrythmogenic doses enhances glycogenolysis in the heart proportionally to the dose used Block of beta-adrenergic receptors by propranolol decreased the activation of glycogenolysis in the ischaemic zone and the frequency of ventricular fibrillation after occlusion of the coronary artery. Exhaustion of noradrenaline reserves by reserpin does not influence the intensity of glycogenolysis and the frequency of fibrillation in the acute period of myocardial infarction. It is believed that the activation of glycogenolysis in experimental myocardial infarction is related to the action of adrenalin.

Topics: Animals; Arrhythmias, Cardiac; Dogs; Epinephrine; Glycogen; Male; Myocardial Infarction; Myocardium; Norepinephrine; Propranolol; Receptors, Adrenergic, beta; Reserpine; Ventricular Fibrillation

The effects of long-term administration of prenylamine gluconate were studied to define changes induced by chronic treatment that may alter the responses of the myocardium to ischaemic stress. Prenylamine gluconate was administered orally to rats (10 mg or 100 mg/kg per day) for 2 weeks. At the end of this period, hearts were excised for perfusion studies. In comparison with gluconate-treated controls, hearts from the group treated with the lower dose of prenylamine showed a significant reduction in basal cardiac function that was not apparent in the group treated with the higher dose of prenylamine. After a period (35 min) of ischaemia stress (reduced flow), a reduction in enzyme leakage and an increase in post-ischaemic functional recovery were observed in hearts from animals treated with the lower dose of prenylamine. In contrast, hearts from the group treated with the higher dose showed no significant improvement. However, chronic prenylamine therapy was shown to reduce in a dose-dependent manner the incidence of post-ischaemic arrhythmias. Thus, although the antiarrhythmic efficacy of long-term treatment with this agent appears to be proportional to the dosage, the ability of prenylamine to reduce ischaemic damage and promote functional recovery does not show a linear relationship with the drug dose.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Coronary Disease; Dose-Response Relationship, Drug; Glycogen; Heart; Heart Function Tests; Male; Myocardium; Perfusion; Phosphocreatine; Prenylamine; Rats; Rats, Inbred Strains

Mechanisms whereby glucose reduces the incidence of pyruvate induced reperfusion arrhythmias in isolated guinea-pig hearts have been investigated. Alterations in cytoplasmic ATP/ADP ratios, creatine phosphate and glycogen were excluded as possible mechanisms. Likewise, data are presented that appear to be at variance with the proposition that glycolytically derived ATP may play a special role in the maintenance of electrical stability. To explain the anti-arrhythmic effects of glucose in terms of this thesis it is necessary to invoke compartmentation of glycolysis. A correlation between the incidence of arrhythmias and glycolytic ATP production can only exist if the contributions to glycolytic flux from glucose and glycogen utilisation can be regarded as separate.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Energy Metabolism; Glucose; Glycogen; Glycolysis; Guinea Pigs; In Vitro Techniques; Myocardium; Perfusion; Pyruvates

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Glycogen; Male; Myocardium; Phosphorylases

One hundred seventeen patients undergoing elective coronary bypass were divided into four groups according to prebypass myocardial glycogen levels and the use of potassium chloride cardioplegia. Myocardial glycogen levels were enhanced with a preoperative fat loading diet and overnight glucose loading. The control group (n = 27) which had mean cardiac glycogen levels of 750 mg/100 gm heart weight and no cardioplegia, had a transmural myocardial infarct rate of 14.4%; 35% had severe atrial arrhythmias 65% had severe ventricular arrhythmias, and 31% had severe vasopressor dependence. The group (n = 30) with low cardiac glycogen (736 mg/100 gm) and with potassium chloride cardioplegia had an infarct rate of 6.4%; 6.7% had severe atrial arrhythmias, 18% had severe ventricular arrhythmias, and 16.7% had severe vasopressor dependence. However, the group (n = 26) which had high cardiac glycogen levels (1,208 mg/100 gm) and no cardioplegia had no myocardial infarctions; 3.8% had severe atrial arrhythmias, 27% had severe ventricular arrhythmias, and only 7.8% had severe vasopressor need. The group (n = 34) which had high glycogen levels (1,516 mg/100 gm) and potassium chloride cardioplegia did best of all with no myocardial infarctions or no severe atrial arrhythmias; 14% had severe ventricular arrhythmias and 2.81% severe vasopressor need. The lessening of vasopressor dependence and severe atrial and ventricular arrhythmias were significant by chi square contingency tables at p less than 0.05 and p less than 0.001, respectively. One cardiac-related death each occurred in the two groups with low glycogen and none in those with high glycogen levels. This suggests that better preoperative cardiac nutrition as represented by enhanced cardiac glycogen helps that heart tolerate anoxic stress whether cardioplegia is utilized or not and is additive to potassium chloride cardioplegia.

Topics: Aorta; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Constriction; Coronary Artery Bypass; Coronary Disease; Dietary Fats; Energy Intake; Female; Glucose; Glycogen; Heart Arrest, Induced; Humans; Intraoperative Complications; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Myocardium; Postoperative Complications; Potassium Chloride; Preoperative Care; Prospective Studies

The incidence of arrhythmias, low output and acute myocardial infarction in the perioperative period was analyzed for 119 patients who underwent aortocoronary bypass surgery. The incidence for three groups of patients was as follows: 44% for 72 patients who did not receive glucose-insulin-potassium (GIK) before operation (no-GIK group), 32% for 25 patients who received preoperative GIK alone before operation (GIK group) and zero in 22 patients who received GIK before operation plus a bolus of 50% glucose (0.5 ml/kg body weight) at the beginning of operation (GIK-G group) (the difference between the GIK-G group and the other two groups is significant; P less than 0.001). Determination of myocardial glycogen content of 63 ventricular biopsies revealed a 2+ to 4+ content in 48% of the no-GIK group, 83% of the GIK group and 100% of the GIK-G group (P less than 0.05). The incidence of complications in patients with myocardial glycogen content of 2+ to 4+ was significantly lower (P less than 0.005) than in those with myocardial glycogen content of 1+. Experimentally, myocardial tolerance to ischemic injury parallels myocardial glycogen content. Our preliminary observation that prior administration of GIK-G increases myocardial glycogen content with a concomitant reduction in complications is consistent with these experimental observations.

Topics: Adult; Arrhythmias, Cardiac; Coronary Artery Bypass; Female; Glucose; Glycogen; Humans; Insulin; Male; Middle Aged; Myocardial Infarction; Myocardium; Potassium

Multifocal Purkinje cell tumors were found in the heart of a nine-month-old black female infant who died with arrhythmias which had become progressively more frequent and severe until they were completely intractable. The Purkinje cell tumors were composed of exactly the same type of cells found in the left bundle branch and the right bundle branch, and they were also located in the expected region of the His bundle. In none of these locations were these Purkinje cells forming normal longitudinally oriented Purkinje fibers, however, and no such fibers were found anywhere in this heart. The cells of the tumors contained glycogen but not in excess of that normally expected to be present in Purkinje cells. No evidence for a generalized abnormality of glycogen metabolism or storage was present. Except for the Purkinje cells, the remaining myocardial cells of the heart were all normal. The fundamental fault appeared to be failure of the Purkinje cells to organize into the normal histological pattern which is characterized by longitudinally oriented Purkinje fibers. Instead, all the Purkinje cells were rounded or polygonal and generally aggregated together into small discrete nodules of varying size. Future cases of this nature deserve careful attention to the nature of their cardiac rhythm and conduction, and in fatal cases there should be special studies of the histological appearance of their cardiac centers of impulse formation and conduction.

Topics: Arrhythmias, Cardiac; Autopsy; Cell Differentiation; Diagnosis, Differential; Electrocardiography; Female; Glycogen; Glycogen Storage Disease; Heart; Heart Diseases; Humans; Inclusion Bodies; Infant; Microscopy, Electron; Myocardium; Purkinje Cells

Trapymin (TM) relaxed excised renal, coronary, pulmonary, femoral and mesenteric arteries and this relaxation was not antagonized by propranolol. The dose-response curve of TM was parallel to that of nitroglycerin and papaverine and steeper than that of dipyridamol or adenosine. TM exerted inotropic and chronotropic actions on excised rat atrium. TM was also effective through the oral route and the effectiveness tended to decrease slightly after repeated use for ten days. TM was effective on vasopressin induced angina in rats and electrocoagulation-induced myocardial infarction. TM suppressed adrenaline-induced arrhythmia but not CaCl2-induced arrhythmia. TM reduced catecholamine content in brain, adrenals and heart but had no influence on monoamine oxidase or dopamine-beta-hydroxylase. TM revealed ganglion-blocking and neuron-blocking actions in cervical ganglion in cats. With propranolol, TM-induced hyperglycemia and reduction in glycogen content in liver and heart was antagonized but TM-induced rise in free fatty acid in serum was not antagonized. Na+-K+ dependent ATPase of bovine heart and P/O ratio of mitochondria of rat heart was not influenced by TM. ADP-induced aggregation of platelets was antagonized by TM. These data indicate that TM induced coronary dilation is partly due to a papaverine like action and also to ganglion-blocking, neuron-blocking and anti-adrenergic action. On the other hand, TM possessed catecholamine release and cardiotonic action as related to beta-receptors.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Blood Glucose; Calcium Chloride; Catecholamines; Cats; Cattle; Coronary Circulation; Dopamine beta-Hydroxylase; Epinephrine; Female; Glycogen; In Vitro Techniques; Isoproterenol; Male; Monoamine Oxidase; Myocardial Contraction; Myocardial Infarction; Myocardium; Platelet Aggregation; Propranolol; Pyrimidines; Rabbits; Rats; Trapidil; Vasodilator Agents; Vasopressins

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bradycardia; Dextrans; Electrocardiography; Energy Metabolism; Flavin-Adenine Dinucleotide; Glycogen; Lysine; Microcirculation; Mitochondria, Muscle; Molecular Weight; Myocardium; NAD; Oxidative Phosphorylation; Oxygen Consumption; Phosphorus; Phosphorylases; Rabbits; Stimulation, Chemical; Succinates; Vasopressins

Topics: Accidents, Aviation; Aerospace Medicine; Arrhythmias, Cardiac; Glycogen; Humans; Hypoxia; Lactates; Myocardium; Postmortem Changes; Potassium; United States

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bradycardia; Coronary Circulation; Dextrans; Electrocardiography; Erythrocyte Aggregation; Glucosyltransferases; Glycogen; Heart; Hypoxia; Microcirculation; Mitochondria, Muscle; Myocardium; Oxidative Phosphorylation; Phosphocreatine; Rabbits; Rats; Vasopressins

Topics: Anaerobiosis; Animals; Arrhythmias, Cardiac; Blood Glucose; Disease Models, Animal; Dogs; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Insulin; Lactates; Myocardial Infarction; Myocardium; Rats

1. Experimental cardiac arrhythmias were produced in dogs anaesthetized with pentobarbitone. Ventricular arrhythmias were induced by strophanthin-K, light petroleum plus adrenaline or coronary ligation procedures. Atrial flutter was induced by an injury-stimulation technique. The acetylcholine and glycogen concentrations of the atria and ventricles were estimated.2. Physostigmine pretreatment (0.1 mg/kg) significantly reduced the incidence of ventricular arrhythmias after myocardial ischaemia but had no effect on any of the other arrhythmias.3. Physostigmine markedly increased the acetylcholine concentrations of atria and ventricles in control dogs, to nearly the same extent. Physostigmine had no effect on ventricular acetylcholine concentrations in dogs treated with strophanthin-K and light petroleum plus adrenaline but in the coronary ligation group it caused a significant increase in the acetylcholine concentrations of both atria and ventricles, and of atrial acetylcholine only in the injury-stimulation group.4. All the arrhythmias produced marked glycogenolysis of both the atria and the ventricles, to nearly the same extent. Although physostigmine produced marked glycogenolysis in the control dogs it significantly inhibited cardiac glycogenolysis after light petroleum plus adrenaline, atrial glycogenolysis after strophanthin-K-induced arrhythmias and ventricular glycogenolysis after myocardial ischaemia.5. There appears to be a possible correlation between the increase in the acetylcholine concentration of the ventricles and anti-arrhythmic actions of physostigmine, but there is a less clear correlation between changes in the glycogen concentration of ventricles and the anti-arrhythmic action.

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Atrial Flutter; Coronary Vessels; Dogs; Female; Glycogen; Heart Atria; Heart Ventricles; Ischemia; Ligation; Male; Petroleum; Physostigmine; Strophanthins; Wounds and Injuries

Topics: Acute Disease; Adenosine Triphosphate; Alkaloids; Animals; Arrhythmias, Cardiac; Asphyxia; Drug Synergism; Electrocardiography; Epinephrine; Fluorides; Glycogen; Hypercapnia; Male; Norepinephrine; Quinidine; Rats; Vasopressins

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

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Endoplasmic Reticulum; Glycogen; Heart Conduction System; Mitochondrial Swelling; Myofibrils; Perfusion; Rats; Sinoatrial Node; Time Factors

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Dogs; Glycogen; Histocytochemistry; Humans; Hydrogen; Hypoxia; Ischemia; Lactates; Mitochondria; Myocardial Infarction; Myocardium; Phosphates

Topics: Animals; Arrhythmias, Cardiac; Catecholamines; Cats; Cocaine; Ethanolamines; Glucose; Glycogen; Heart; Heart Rate; Lactates; Myocardium; Oxygen; Perfusion; Pyruvates

Topics: Arrhythmias, Cardiac; Enzymes; Geriatrics; Glycogen; Heart Block; Heart Conduction System; Hemochromatosis; Humans; Iron; Myocardium; Pathology

Topics: Arrhythmias, Cardiac; Blood Flow Velocity; Coronary Vessels; Glycogen; Heart; Lactates; Metabolism; Pharmacology; Rats; Research; Reserpine; Strophanthins

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Glycogen; Heart; Heart Conduction System; Myocardium; Phosphorylases; Phosphotransferases