Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzymes in the human myocardium following sudden death were examined for activity in a quantitative histoenzymological study, these were NAD-dependent dehadrogenases of succinate (SDG), lactate (LDG), beta-hydroxybutyrate (beta-HOBDG), alpha-glycerophosphate (alpha-GPDG), alcohol (ADG), glucoso-6-phosphate (G-6-PDG), and NAD-diaphorase (NADse), and catalase. Autopsies were performed within 3 h after death. beta-HOBDG and LDG were found to show an increase in activity in the cardiomyocytes of sudden death subjects with coronary heart disease without apparent changes. In the myocardium from death subjects with coronary heart disease and large postinfarct cardiosclerosis, the activity of the enzymes was directly related to the severity of myocardial hypertrophy and signs of chronic heart failure. As myocardial hypertrophy developed, the enzyme activity increased; when there appeared signs of chronic heart failure it decreased. The myocardium from sudden death subjects with alcoholic cardiomyopathy showed diminished redox enzyme activity and higher activity of the enzyme utilizing alcohol (ADG and catalase). The findings suggest that changes in the enzyme activity in the myocardium are of various type and depend on previous cardiac abnormalities.
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PMID:Quantitative histoenzymological characteristics of the myocardium in sudden cardiac death. 252 98

Phosphorus 31 magnetic resonance spectroscopy (MRS) can be used to monitor the direct effect of drugs on energy metabolites of the heart. Using the isolated perfused heart of the cardiomyopathic hamster (late heart failure), drugs that exacerbate the diastolic level of calcium [Ca]i (e.g., dobutamine and digoxin) augment intracellular phosphomonoester sugars, while drugs which increase cyclic adenosine mono-phosphate [cAMP]i (e.g. isoprel, dibutyryl cAMP, and amrinone) lower phosphomonoester sugars. The phosphomonoester sugars are inversely related to developed pressure and oxygen consumption. Accumulation of sugar phosphates indicates inhibition of glycolysis and limited delivery of pyruvate to the mitochondria, thereby decreasing oxygen consumption. The phosphorylation potential obtained from standardized 31P MRS values showed a direct relationship to the rate pressure product in hamsters with heart failure; however, the two parameters were inversely related in control hamsters.
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PMID:Influence of drugs on diseased states of the heart. A 31P NMR and [Ca]i study. 260 35

A boy born at full-term died after 14 days from cardiac failure. At autopsy DiGeorge complex was diagnosed. The father was found to have facial dysmorphia and hypocalcaemia. Investigations revealed no cause other than hypoparathyroidism associated with normal serum 1,25-dihydroxyvitamin D concentrations and normal renal handling of phosphate. Immunological tests, performed on two occasions with an interval of 9 months, revealed a decrease in the number of CD8+ lymphocytes, compatible with a partial thymus deficiency. The combination of facial dysmorphia with dysfunction of the thymus and the parathyroid glands can constitute a partial DiGeorge complex. The findings in this family are compared with reports of four other families with DiGeorge complex in two generations. In genetic counseling DiGeorge complex should be considered a heterogenous disorder. Screening of the parents for somatic stigmata, hypocalcaemia, disturbed cellular immunity, cardiac and chromosomal abnormalities is essential.
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PMID:Facial dysmorphia, parathyroid and thymic dysfunction in the father of a newborn with the DiGeorge complex. 261 7

Denopamine (DP) is a new, orally active, selectively positive inotropic agent and used for the treatment of chronic cardiac insufficiency. The therapeutic effects of DP is highly related to its serum concentrations. A simple analytical method has been developed to determine the serum concentration of DP by use of high performance liquid chromatography (HPLC) with electrochemical detection (ECD). In order to extract the DP from the serum, a disposable solid extraction column (Sep-Pak cartridge, C-18) was used. The average recovery was 84.6 +/- 2.7%. The working electrode potential was fixed at 400 mV with a T1 cell, 600 mV with a T2 cell and 650 mV with a Guard cell in ECD. The analysis was performed on a Nova-Pak cartridge C-18 reverse-phase column (100 mm X 8 mm i.d., 4 microns). The mobile phase consisted of 0.1 M potassium phosphate buffer (pH 6.0) and acetonitrile (83: 17, v/v), and the flow rate was 1.0 ml/min. DP and internal standard phenolphthalein (PP) were eluted at 16.5 and 36.0 min, respectively. The peak-height ratio of DP to PP was linearly correlated (r = 0.9998) over a concentrations range between 1.25 and 15.0 ng/ml in the serum. The lowest detectable concentration was 1.0 ng/ml in the serum. The coefficient of variation of reproducibility in the assay was 6.0% By using the present method, serum concentration of DP was measured for four healthy volunteers after a single oral administration of 10 mg DP tablet after a overnight fast. From these DP concentration profiles, pharmacokinetic parameters were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Development of a simple analytical method to determine the serum concentration of denopamine by high performance liquid chromatography with electrochemical detection and its clinical application]. 261 68

Dobutamine has been shown to exert disparate clinical effects in patients with cardiomyopathy and heart failure. This study evaluated the effects of dobutamine on hemodynamics and energetics in isolated, perfused myopathic hamster hearts at a moderate and advanced stage of heart failure. Biochemical changes were correlated with left ventricular developed pressure, coronary flow, and myocardial oxygen consumption. During dobutamine treatment left ventricular developed pressure increased in the control and moderate heart failure group 28.0 +/- 1.0% and 114.2 +/- 11.6%, respectively. Myocardial oxygen consumption increased 50.1 +/- 9.1% and 45.5 +/- 16.0%, respectively. There were no significant changes of left ventricular developed pressure and myocardial oxygen consumption in the advanced heart failure group. Inorganic phosphate (Pi) increased in the control group from 6.8 +/- 0.5 to 11.4 +/- 1.2 mmol (p less than 0.005) and in the advanced heart failure group from 10.4 +/- 1.1 to 15.3 +/- 1.2 mmol (p less than 0.01). Phosphocreatine (PCr) and beta-ATP (adenosine triphosphate) decreased in the control group from 12.2 +/- 0.4 to 8.7 +/- 0.7 mmol (p less than 0.001) and 10.4 +/- 0.8 to 7.7 +/- 0.7 mmol (p less than 0.02), respectively. PCr/Pi ratio, reflecting mitochondrial function, fell in the control and advanced heart failure group from 1.84 +/- 0.14 to 0.84 +/- 0.14 (p less than 0.02) and 0.81 +/- 0.16 to 0.37 +/- 0.08 (p less than 0.03), respectively. Thus in cardiomyopathic hamsters dobutamine improved mechanical performance and thermodynamic efficiency in moderate stages of heart failure by improving mitochondrial activity, but did not improve mechanical performance in an advanced stage of heart failure. These experiments provide into the disparate clinical effects of dobutamine at various stages of heart failure.
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PMID:The effect of dobutamine on myocardial performance and high-energy phosphate metabolism at different stages of heart failure in cardiomyopathic hamsters: a 31P MRS study. 266 31

Nuclear magnetic resonance spectroscopy has great potential for defining noninvasively the metabolic status of the heart and skeletal muscle. This technique uses the spin properties of certain nuclei (such as phosphorus-31, hydrogen-1 and carbon-13) to measure high energy phosphates, intracellular pH, lactate and glycogen. Animal studies have formed the basis for human investigations and have demonstrated well-defined changes in high energy phosphates during myocardial ischemia and reperfusion, as well as in cardiomyopathies. Human studies have been limited by issues of sensitivity and localization, although techniques such as rotating frame, depth-resolved surface coil spectroscopy, image-selected in vivo spectroscopy and spectroscopic imaging have been used to acquire phosphorus-31 spectra from the human heart. The few human studies of patients with disease have demonstrated elevated inorganic phosphate peaks after myocardial infarction and abnormal phosphodiester peaks in patients with hypertrophic cardiomyopathy. Studies of patients with heart failure have shown that these patients acidify their peripheral muscles with exercise more easily than do control subjects. Clinical application of nuclear magnetic resonance spectroscopy will depend on technical advances and the demonstration of sensitivity of metabolic changes with disease.
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PMID:Cardiovascular applications of nuclear magnetic resonance spectroscopy. 267 66

Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure (peak VO2, 15.4 +/- 4.7 ml/kg/min; ejection fraction, 20 +/- 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers (normal subjects, 22.7 +/- 10.1; heart failure, 33.1 +/- 11.1%; p less than 0.05), atrophy of type IIa (normal subjects, 5,477 +/- 1,109; heart failure, 4,239 +/- 1,247 microns 2; p less than 0.05) and type IIb fibers (normal subjects, 5,957 +/- 1,388; heart failure, 4,144 +/- 945 microns 2; p less than 0.01), and decreased activity of beta-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 +/- 1.44; heart failure, 3.67 +/- 1.68 mol/kg protein/hr; p less than 0.05). No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. 280 70

The acute and prolonged effects of alcohol and smoking on the oxidative and energy processes of cardiac muscle in experimental animals were studied at the subcellular level. The acute effect of alcohol manifested itself by decreasing mitochondrial respiration, compensated by increased glycolytic activity of the myocardium so that myocardial energy phosphate concentration remained unchanged. The prolonged effect of alcohol (for a period of 14 days) resulted in a decrease in oxidative processes as well as in glycolytic activity with a subsequent decline in myocardial ATP and CP levels. Smoking led to a significant decrease in oxidative and total bioenergetic processes of cardiac muscle mitochondria both after acute and prolonged smoking. This metabolic disorder is localized in the terminal segment of the respiratory chain of the mitochondria at the level of cytochrome oxidase. The authors conclude that the above-mentioned disorders may play a role in the development of heart failure on the basis of alcoholic or smoke cardiomyopathy.
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PMID:Metabolic disorders of cardiac muscle in alcoholic and smoke cardiomyopathy. 280 6

The oxidative phosphorylation as well as calcium transporting properties of heart mitochondria and calcium transport activities of the fragments of the sarcoplasmic reticulum (microsomes) were studied during the life span of cardiomyopathic hamsters (UM-X7.1). Control healthy hamsters of the same age group were used for comparison. No changes in the oxidative phosphorylation ability of cardiomyopathic mitochondria were seen at early and moderate stages of heart failure; however, at severe stages, mitochondrial respiratory functions, but not the ADP:0 ratio, were impaired. Both creatine phosphate and ATP contents were decreased without any significant changes in the ATPase activities of myofibrils from the failing hearts. Heart mitochondria from cardiomyopathic animals at severe stages of failure exhibited less calcium binding and uptake activities in comparison with the control values whereas no changes in the mitochondrial calcium binding and uptake were seen in cardiomyopathic hamsters which showed no clinical signs of heart failure. Although mitochondrial calcium binding in cardiomyopathic hearts at early and moderate stages of failure was decreased, mitochondrial calcium uptake was not significantly different from the control. Microsomal calcium binding activity, unlike calcium uptake activity, was decreased in the hearts of cardiomyopathic hamsters without any signs of heart failure. Both calcium binding and calcium uptake activities of microsomes from animals with early, moderate and severe heart failure were less in comparison with the control values but were not associated with any changes in the Ca2+-stimulated ATPase activity. These results suggest that changes in the process of mitochondrial energy production and mitochondrial Ca2+-transport may be secondary to other factors whereas alterations in the sarcoplasmic reticular Ca2+-transport may lead to the development of heart failure in the cardiomyopathic hamsters.
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PMID:Impairment of mitochondrial and sarcoplasmic reticular functions during the development of heart failure in cardiomyopathic (UM-X7.1) hamsters. 294 28

Cardiac failure appears rapidly during severe hypoxia and precedes a substantial reduction in adenosine triphosphate content. Reduced adenosine triphosphate turnover, in the presence of nearly normal content, may be the metabolic basis for contractile failure during hypoxia. To measure both the myocardial content and the turnover rates of high-energy phosphate compounds during hypoxia, we performed 31P-nuclear magnetic resonance studies by placing a surface coil directly over the left ventricle in intubated rats that were instrumented for hemodynamic measurements and ventilated with either 21, 10, or 8% O2. Normoxia produced a hemodynamic and metabolic steady state for 4 hours and hypoxia for at least 60 minutes. Under normoxic ventilation (n = 10, mean +/- SD), the arterial PO2 was 96 +/- 14, pH 7.38 +/- 0.11, and systolic blood pressure 96 +/- 8 mm Hg; under hypoxic ventilation with 10% O2 (n = 5), the arterial PO2 was 57 +/- 10, pH 7.39 +/- 0.09, and systolic pressure 68 +/- 10; and under hypoxic ventilation with 8% O2 (n = 5), the PO2 was 52 +/- 7, pH 7.37 +/- 0.04, and systolic pressure 51 +/- 4. Hypoxic ventilation with 10 or 8% O2 decreased the creatine phosphate content from 51.4 +/- 5.4 mumol/g dry wt to 39.3 +/- 5.4 and 45.6 +/- 4.1 and depressed adenosine triphosphate slightly from 25.0 mumol/g dry wt to 21.8 +/- 2.1 and 21.9 +/- 1.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contractile failure and high-energy phosphate turnover during hypoxia: 31P-NMR surface coil studies in living rat. 295 20


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