ascorbic-acid and Cardiomyopathies

Sepsis care has evolved significantly since the initial early goal-directed therapy (EGDT) trials. Early fluid resuscitation, source control, and antibiotic therapy remain cornerstones of care but overall understanding is more nuanced, particularly regarding fluid selection, vasopressors, and inotropic support. Timely nutrition therapy and ventilatory support tend to receive less attention but also are important. Recent research has explored immunomodulation, β-blockade, and vitamin supplementation. A renewed emphasis on early, aggressive resuscitation reaffirms the importance of emergency medicine providers knowledgeable and skilled in sepsis management.

Topics: Angiotensin II; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Blood Glucose; Blood Pressure; Cardiomyopathies; Cardiotonic Agents; Critical Illness; Emergency Service, Hospital; Enteral Nutrition; Fluid Therapy; Glucocorticoids; Hemodynamics; Humans; Organ Dysfunction Scores; Randomized Controlled Trials as Topic; Respiration, Artificial; Resuscitation; Sepsis; Vasoconstrictor Agents

The anthracycline antibiotic adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a wide variety of cancers. However, its use is seriously limited by the development in the heart of acute and chronic toxic effects. Mechanisms of action and toxicity of adriamycin are briefly revised in this review. Among followed strategies to attenuate adriamycin toxicity are dosage optimisation, synthesis and use of analogues or combined therapy with antioxidants. The most promising results come from the combination of the drug delivery together with an antioxidant in order to reduce oxidative stress. Many antioxidants have been assayed with very different results. Among these molecules, metal ions chelators and low-molecular-mass agents that scavenge reactive oxygen species and that are synthesised in vivo have been widely studied. However, the present review will be exclusively focused on the antioxidants that are derived from the diet, in particular the role of vitamin E, vitamin C, vitamin A, coenzyme Q, flavonoids, antioxidant components of virgin olive oil and selenium.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cardiomyopathies; Curcuma; DNA Damage; Doxorubicin; Female; Flavonoids; Humans; Olive Oil; Phenols; Plant Oils; Polymers; Rats; Reactive Oxygen Species; Selenium; Ubiquinone; Vitamin A; Vitamin E

Topics: Adolescent; Adult; Ascorbic Acid; Blood Transfusion; Cardiomyopathies; Deferoxamine; Dose-Response Relationship, Drug; Ferritins; Growth Disorders; Heart Diseases; Hemosiderosis; Humans; Iron; Iron Chelating Agents; Liver; Liver Diseases; Pancreatic Diseases; Parathyroid Diseases; Pituitary Diseases; Thyroid Function Tests

Cigarette smoking causes a vast array of diseases including cardiovascular diseases. Our laboratory focuses on investigating cigarette smoke (CS)-induced cardiovascular malfunction and the responsible mechanisms utilizing the model, c-kit-positive cardiac stem cells (CSCs). The main objective of our study is to investigate whether CS extracts (CSEs) cause impairment of CSC functions via oxidative damage. We hypothesized that CSE, via oxidative modifications of CSC proteins and antioxidant enzymes, can modulate CSC functions and these modifications can be attenuated by ascorbate treatment. Our specific aims are (1) to investigate CSE-induced oxidative modification of CSC proteins via carbonylation, and prevention by ascorbic acid; (2) to investigate CSE-induced oxidative modification of antioxidant enzymes and ascorbic acid-mediated modulations; and (3) to investigate CSE-induced changes in CSC functions and protection by ascorbic acid. CSCs were cultured, and the aqueous extracts of CSE were prepared. CSE-induced modulations of CSC viability, oxidative modification of proteins, and antioxidant enzyme activities were detected using standard assays including Apostain, bromodeoxyuridine, and Oxiblot. CSE caused oxidative modification of CSC proteins, changed antioxidant enzyme levels, attenuated CSC proliferation, and accelerated CSC apoptosis. Ascorbic acid prevented CSE-induced CSC malfunctions, and ascorbic acid therapy might be useful in smoker CSC recipients and to condition CSCs prior to the transplant in the future. Cardiac stem cell therapy is currently undergoing in clinical trials.

Topics: Animals; Ascorbic Acid; Cardiomyopathies; Cells, Cultured; Myoblasts, Cardiac; Oxidative Stress; Rats; Rats, Inbred F344; Smoke; Tobacco Smoke Pollution; Vitamins

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Antioxidants; Ascorbic Acid; Cardiomyopathies; Cardiotonic Agents; Cytokines; Doxorubicin; Electrocardiography; Male; Nitric Oxide Synthase; Oxidative Stress; Oxygen Consumption; Rats; Rats, Wistar; Reactive Nitrogen Species; Stress, Physiological; Survival Analysis

Increased production of oxygen free radicals and decreased oxidant capacity occur in coronary artery diseases (CAD) This pro-oxidant shift in intracellular redox state may induce cell death by either direct cell membrane damage by lipic peroxidation or apoptosis through activation of transcription factors. These changes occur not only in cardiomyocytes, bu also in cardiac sympathetic nerves, which are very sensitive to oxidative damage. Patients with heart failure encountel reduced peripheralblood flow at rest, during exercise and in response to endothelium-dependentvasodilators. Current treatments of cardiomyopathy, a degenerative condition of the myocardium frequently associated with heart failure have done little to enhance patient survival. Decreased myocardial contractility and altered regulation of peripheral circulation along with oxidative conditions are important contributors to the symptoms and prognosis of the disease process. Nitric oxide formed from L-arginine (2-amino-5 guanidinovaleric acid) metabolism in endothelial cells contributes to regulation of blood flow under these conditions. L-Arginine is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. In the present study, we investigated the effect of oral administration of L-arginine (3 g/day) on the intracellular redox status of the patients of ischemic cardiomyopathy aged 45-60 yrs. The enzymatic and non-enzymatic antioxidant parameters like superoxide dismutase, catalase, total thiols (TSH) and ascorbic acid along with pro-oxidant parameters, such as xanthine oxidase, as well as index of oxidative stress as protein carbonyl content and malondialdehyde (a marker of lipid peroxidation) were investigated in the plasma and RBC lysate. L-Arginine (3 g/day) administration was found to improve the levels of these parameters in the patients and regulate the blood flow, as evident by the improved blood pressure of the patients. Thus, it is inferred that L-arginine attenuates the oxidative stress conditions along with maintaining the blood pressure rate of patients suffering from cardiomyopathy.

Topics: Antioxidants; Arginine; Ascorbic Acid; Cardiomyopathies; Catalase; Coronary Artery Disease; Female; Free Radicals; Humans; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Oxidants; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Thyrotropin; Xanthine Oxidase

Understanding the molecular basis of doxorubicin (Dox)-induced cardiomyopathy is crucial to finding cardioprotective strategies. Oxidative stress-mediated pathways are known to contribute to cardiomyocyte apoptosis due to Dox. Improving the antioxidant defenses of cardiomyocytes could be one strategy for cardiac protection. We tested the effects of vitamin C (Vit C), a potent antioxidant, on Dox-induced cardiomyocyte apoptosis. Adult rat cardiomyocytes were incubated for 24 h with Dox (0.01-10 μM), with and without different concentrations of Vit C (5-100 μM). Exposure to Dox (10 μM) resulted in a 98% increase in the production of reactive oxygen species (ROS) and creatine kinase (CK) release, 70% increase in p53 as well as ASK-1 activation, 40% increase in p38 activation, 30% increase in pro-apoptotic Bax over anti-apoptotic Bcl-xl ratio and caspase activation, and about 20% reduction in cell viability. Vit C (25 μM) was able to mitigate Dox-induced changes by decreasing ROS and CK release by 50%, reducing p53 activation by 40%. The increase in ASK-1 and p38 was also significantly mitigated, and apoptosis was reduced while cardiomyocytes viability was improved. This study shows that Dox-induced cardiomyocyte death is mediated by a direct membrane effect as well as intracytoplasmic changes promoting the cardiomyocyte apoptosis. These findings suggest a nutritional approach of using Vit C for preventing Dox-induced cardiotoxicity and better management of cancer patients.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Ascorbic Acid; Cardiomyopathies; Cardiotonic Agents; Cell Survival; Cells, Cultured; Creatine Kinase; Dose-Response Relationship, Drug; Doxorubicin; Enzyme Activation; Male; MAP Kinase Kinase Kinase 5; Myocytes, Cardiac; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Permeability; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tumor Suppressor Protein p53

To evaluate the mechanisms and the impact of the angiotensin-converting enzyme inhibitor perindopril (P) in a model of doxorubicin (D)-induced cardiotoxicity, male Wistar rats received D (1 mg/kg/d, IP for 10 days), P (2 mg/kg/d by gavage from day 1 to day 18), D (for 10 days) + P (for 18 days) or saline. D decreased systolic blood pressure and body and heart weights. Left ventricular diastolic diameter was increased by D (P < 0.01), but it was not attenuated by P. D decreased plasma vitamin C (P < 0.05) and increased the ascorbyl radical/vitamin C ratio (P < 0.01). This ratio was attenuated by P. No difference was found among groups in cardiac troponin I, brain natriuretic peptide concentrations, and tissue oxidative stress (OS). Myocardial MCP-1 expression was higher in the D group. Cardiac kinin receptor (B1R and B2R) expression was not affected by D, yet binding sites for B2R and B1R were increased in D+P and P groups, respectively (P < 0.05). In conclusion, D induced cardiac functional alterations, inflammation and plasma OS whereas tissue OS, and cardiac kinin receptors expression were not modified. P did not improve cardiac performance, but it modulated kinin receptor expression and enhanced antioxidant defense.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antibiotics, Antineoplastic; Ascorbic Acid; Binding Sites; Blood Pressure; Cardiomyopathies; Chemokine CCL2; Doxorubicin; Gene Expression Regulation; Male; Natriuretic Peptide, Brain; Oxidative Stress; Perindopril; Rats; Rats, Wistar; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Troponin I

We addressed a potential mechanism of myocardial dysfunction following coronary microembolization at the level of myofibrillar proteins.. Anaesthetized pigs underwent intracoronary infusion of microspheres. After 6 h, the microembolized areas (MEA) had decreased systolic wall thickening to 38 +/- 7% of baseline and a 2.62 +/- 0.40-fold increase in the formation of disulphide cross-bridges (DCB) in tropomyosin relative to that in remote areas. The impairment in contractile function correlated inversely with DCB formation (r = -0.68; P = 0.015) and was associated with increased TNF-alpha content. DCB formation was reflected by increased tropomyosin immunoreactivity and abolished in vitro by dithiothreitol. Ascorbic acid prevented contractile dysfunction as well as increased DCB and TNF-alpha. In anaesthetized dogs, 8 h after intracoronary microspheres infusion, contractile function was reduced to 8+/-10% of baseline and DCB in MEA was 1.48+/-0.12 higher than that in remote areas. In conscious dogs, 6 days after intracoronary microspheres infusion, myocardial function had returned to baseline and DCB was no longer different between remote and MEA. Again contractile function correlated inversely with DCB formation (r = -0.83; P = 0.005).. Myofibrillar protein oxidation may represent a mechanistic link between inflammation and contractile dysfunction following coronary microembolization.

Topics: Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Cardiomyopathies; Coronary Vessels; Dithiothreitol; Dogs; Embolism; Immunohistochemistry; Microcirculation; Microspheres; Myocardial Contraction; Oxidation-Reduction; Reactive Oxygen Species; Swine; Swine, Miniature; Tropomyosin; Tumor Necrosis Factor-alpha

Exogenous insulin does not prevent cardiac failure in patients with type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed. Certain transition metals are known to act as insulin mimics and may be cardio- protective. In this study, the ability of a newly synthesised molybdenum/ascorbic acid complex to strengthen cardiac function was investigated.. Male CD rats were assigned to one of five groups: non-diabetic control, non-diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated with sodium ascorbate, diabetic treated with molybdenum/ascorbic acid complex and untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once diabetes was confirmed, treatment was initiated by adding either the molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and continued for 6 weeks. Following the treatment period, the animals were terminated, and their hearts were excised and mounted in a working heart perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid level determination. Cardiac function was evaluated using 1 hour of low-flow ischaemic stress followed by 30 minutes of reperfusion.. Hearts from the animals treated with the molybdenum/ascorbic acid complex displayed the best aerobic performance of all the diabetic animals. Blood glucose levels and blood lipid levels were significantly lower in animals treated with the complex than in other diabetic animals. The group treated with the complex also had a lower drinking rate than the other diabetic groups. Furthermore, hearts from animals treated with the molybdenum/ascorbic acid complex showed a greater degree of recovery from low-flow ischaemia than any other group.. The molybdenum/ascorbic acid complex showed some significant insulin-mimic and cardioprotective effects. Further development of this complex could provide a drug useful for alleviating some of the cardiovascular problems associated with diabetes mellitus.

Topics: Animals; Ascorbic Acid; Blood Glucose; Cardiomyopathies; Diabetes Mellitus, Experimental; Heart; Insulin; Lipids; Male; Molybdenum; Myocardial Ischemia; Rats; Rats, Inbred Strains; Streptozocin

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

Cardiac effects of human immunodeficiency virus (HIV) transactivator (Tat) are unclear, but Tat decreases liver glutathione (an important mitochondrial antioxidant) when ubiquitously expressed in transgenic mice (TG). With an alpha-myosin heavy chain promoter, Tat was selectively targeted to murine cardiac myocytes. One high-expression hemizygous ((+/-)Tat(high); 12 copies) and two low-expression ((+/-)Tat(lowA,B); 2-5 copies) TG lines were created. Cardiomyopathy was documented with increased left ventricle (LV) mass, ventricular expression of atrial natriuretic factor (ANF) mRNA, mitochondrial ultrastructural defects, and myocardial depletion of glutathione. In (+/-)Tat(high) TGs, normalized LV mass (determined echocardiographically) increased 46% (90 days), 134% (240 days), and 96% (365 days) compared with wild-type littermates (WT). LV fractional shortening was decreased to 28% (90 days), 27% (240 days), and 19% (365 days). (+/-)Tat(low) LV mass was unchanged (or=210 days); however, profound mitochondrial destruction occurred in homozygous (+/+)Tat(high) hearts (10 days) and the pups died (14 days). Tat caused cardiac dysfunction in this TG and may impact on cardiomyopathy in acquired immunodeficiency syndrome.

Topics: Animals; Antioxidants; Ascorbic Acid; Atrial Natriuretic Factor; Blotting, Western; Cardiomyopathies; Echocardiography; Electrocardiography; Gene Expression; Gene Products, tat; Gene Targeting; Glutathione; Heart Ventricles; Mice; Mice, Transgenic; Microscopy, Electron; Mitochondria, Heart; Muscle, Skeletal; Myocardial Contraction; Myocardium; Organ Specificity; RNA, Messenger

We describe the case of a 36-year-old woman with hereditary hemochromatosis (HH) resulting in end-stage cardiomyopathy and treated successfully with orthotopic cardiac transplantation. Before and after transplantation, the patient underwent aggressive treatment with frequent phlebotomy. We used erythropoietin concomitantly to maintain adequate hematocrit to support continued phlebotomy. We believe that aggressive use of phlebotomy provided the patient hemodynamic benefit and hastened the return of endocrine function post-transplantation. We also believe that the patient's history of high-dose vitamin C usage may have accelerated iron deposition in the heart and other vital organs.

Topics: Adult; Ascorbic Acid; Cardiomyopathies; Combined Modality Therapy; Contraindications; Erythropoietin; Female; Heart Transplantation; Hemochromatosis; Humans; Phlebotomy

Chronic heart failure (CHF) seems to be associated with increased oxidative stress. However, the hypothesis that antioxidant nutrients may contribute to the clinical severity of the disease has never been investigated.. To examine whether antioxidant nutrients influence the exercise capacity and left ventricular function in patients with CHF.. Dietary intake and blood levels of major antioxidant nutrients were evaluated in 21 consecutive CHF patients and in healthy age- and sex-matched controls. Two indexes of the severity of CHF, peak exercise oxygen consumption (peak VO2) and left ventricular ejection fraction (LVEF), were measured and their relations with antioxidants were analysed.. Whereas plasma alpha-tocopherol and retinol were in the normal range, vitamin C (P=0.005) and beta-carotene (P=0.01) were lower in CHF. However, there was no significant association between vitamins and either peak VO2 or LVEF. Dietary intake (P<0.05) and blood levels of selenium (P<0.0005) were lower in CHF. Peak VO2 (but not LVEF) was strongly correlated with blood selenium: r=0.76 by univariate analysis (polynomial regression) and r=0.87 (P<0.0005) after adjustment for age, sex and LVEF.. Antioxidant defences are altered in patients with CHF. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction. Further studies are warranted to confirm the data in a large sample size and to investigate the mechanisms by which selenium and other antioxidant nutrients are involved in CHF.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiomyopathies; Chronic Disease; Feeding Behavior; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress; Selenium; Ventricular Function, Left

Lack of uniform views concerning subcellular image and possible meaning of free radicals in the myocardial damage prompted us to study rat hearts submitted for chronic thyrotoxicosis. The studies were performed on 30 Wistar white rats. The material was obtained from anterior wall of the left ventricle of the heart. To confirm the role of free radicals one group of rats was given ascorbic acid, a well-known substance with anti-oxidation properties (free radical scavenger). In the control group we observed a typical structure of the myocardium. In the group with thyrotoxicosis a great degree of subcellular structural damage was noticed. These alterations correspond to nonspecific myocardial damage that can be meet in hypoxia, reperfusion or in toxic myocardial damage. However, in case of vitamin application generally known to have anti-oxidation properties, damages were significantly less intensive and occurred more rarely. It seems to indicate a significant role of free radicals in the generation of these alterations.

Topics: Animals; Ascorbic Acid; Cardiomyopathies; Female; Free Radicals; Hyperthyroidism; Male; Microscopy, Electron; Myocardium; Rats; Rats, Wistar; Thyroid Diseases; Thyroxine

Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Topics: Allopurinol; Animals; Ascorbic Acid; Body Water; Cardiomyopathies; Coronary Disease; Dogs; Edema; Embolism; Free Radical Scavengers; Free Radicals; Microcirculation; Microspheres; Oxygen; Superoxide Dismutase; Theophylline

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cardiomyopathies; Doxorubicin; Guinea Pigs; Leukemia, Experimental; Lipid Peroxides; Mice; Mice, Inbred Strains; Myocardium; Neoplasm Transplantation

Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.

Topics: Adult; Aorta; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Hyperparathyroidism, Secondary; Lung; Male; Nephritis, Interstitial; Parathyroid Glands; Renal Dialysis; Uremia

Topics: Adult; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Topics: Ascorbic Acid; Cardiomyopathies; Erythrocytes; Glutathione Peroxidase; Hair; Hemoglobins; Hemolysis; Humans; Oxidation-Reduction; Selenium; Superoxides

The incisive detection of bioenergetic insufficiency in an organ of known workload by P MRS is noninvasive and nondestructive, and in some cases the portion of the organ involved can be determined, particularly if both PCr and ATP are depleted. The fractional loss of ATP and hence the relative volumes of viable and "metabolically dead" tissue are thereby evaluated. In addition, the value of P MRS in following a therapy complements its value in diagnosis as this has been demonstrated in cases followed over 6 months to three years. The fact that deficiencies of the enzymes and substrates of oxidative metabolism can be detected by P MRS affords a global overview of energy metabolism that can be a key to rapid diagnosis. The distinction of the enzyme and/or substrate deficiency, while not directly indicated by steady state P MRS, can be identified by use of the "Crossover Theorem" and its impact upon blood and tissue levels of substrates (including oxygen). In the case of neonatal systemic hypoxia, there is no doubt about which of the equations applies, and similarly in metabolic disease, a glutaric acid urea is a direct consequence of the crossover response of metabolism and signifies that an enzyme deficiency may be involved. Furthermore, the clinical danger of a high Pi/PCr value is clarified by our observations, both from the animal models and from the theory, the high clues; i.e. 2 and over, suggest work stresses near the capability of oxidative metabolism and imminent failure of the negative feedback afforded by metabolic regulation, particularly ADP control of oxidative metabolism. This control is lost because of the fall of phosphocreatine to the point where creatine kinase is no longer in equilibrium, leading to the loss of ATP and its conversion to large amounts of ADP and its breakdown products. ATP then stimulates glycolysis and results in a massive lactic acidosis. At the same time, the low thermodynamic capability of glycolytic metabolism is unable to prevent irreversible ion disequilibration, water movements, edema, and eventually rupture of the cell membrane. The pathway of resynthesis of ATP is then tortuous, particularly as AMP is deaminated and adenosine is converted eventually to hypoxanthine. Thus, NMR reports that metabolic control is operating in the region where homeostasis of biochemical parameters is feasible. It further reports regions where the metabolic control is susceptible to failure and most aggressive clinical care is require

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Cardiomyopathies; Electric Organ; Electrophorus; Humans; Hypoxia; Infant, Newborn; Kinetics; Magnetic Resonance Spectroscopy; Metabolic Diseases; Mitochondria; Muscular Dystrophies; Phosphates; Vitamin K

Topics: Ascorbic Acid; Cardiomyopathies; Humans; Iron; Pyruvate Kinase

We describe rapidly fatal cardiomyopathy in a young man. He had for twelve months ingested large amounts of ascorbic acid and was admitted with severe heart failure having been symptomatic for two months. He died after eight days. Idiopathic haemochromatosis was diagnosed at autopsy. The clinical and laboratory features are discussed and the possible implications of ascorbic acid ingestion are explored.

Topics: Adult; Ascorbic Acid; Cardiomyopathies; Heart Failure; Hemochromatosis; Humans; Male; Myocardium

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

Topics: Ascorbic Acid; Cardiomyopathies; Diagnosis, Differential; Electromyography; Female; Humans; Male; Middle Aged; Periodontal Diseases; Scurvy; Tooth Extraction

Topics: Ascorbic Acid; Cardiomyopathies; Child; Cholecalciferol; Coronary Disease; Heart; Humans; Infant; Vitamins