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)

Na+/K(+)-ATPase of the cell membrane is considered to be closely related to the pathology of various diseases including hypertension and heart failure. The activity of this enzyme in the erythrocyte membrane has been determined in earlier reports by the assay of inorganic phosphate generated from the substrate ATP or radioimmunoassay after binding 3H ouabain to the erythrocyte membrane, using a large volume of blood samples. However, as neither method was appropriate for wide routine use, we developed a method to assay this enzyme in a small volume (10 ml) of fresh human blood samples with re-evaluation of conditions for the inorganic phosphate assay. In this method, the coefficient value (CV) of membrane protein amount and the NA+/K(+)-ATPase activity were 2.2% and 2.5% respectively, indicating sufficient precision of the assay. Moreover, in 97 subjects without abnormalities in blood biochemical tests (77 males and 20 females) aged 35-59 years, the enzyme activity showed no differences according to age or sex, ranging from 0.217 to 0.071 mumols Pi/mg/hr with a mean of 0.130.
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PMID:[Determination of human erythrocyte membrane Na+/K(+)-ATPase activity in small volume of blood sample]. 131 73

Mildronat potentiates the therapeutic effect of the combined treatment of heart failure, which includes the use of nitro drugs. It also decreases the level of methemoglobin in the patients' blood and improves the phosphate balance, especially that of 2,3-diphosphoglycerate to control oxygen transport by hemoglobin, which is of paramount importance in hypoxia caused by coronary heart disease.
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PMID:[The characteristics of the action of mildronate (dihydrate 3-(2,2,2-trimethylhydrazine)propionate) on the red blood parameters in heart failure]. 145 54

In myocardial hypertrophy and heart failure a series of adaptational changes occur some multiplying contractile units, others slowing shortening velocity and increasing economy of contraction. The demonstration of energy-saving mechanisms in heart failure has prompted further investigations of energy providing and utilizing metabolic pathways. The use of myocardial ATP as a substrate occurs mainly at the myosin-ATPase and at the Ca-ATPase of the sarcoplasmic reticulum. As the Michaelis constant of both enzymes for ATP is in the micromolar (microM) range, whereas cellular ATP content is about 5000 microM, these enzymes are not controlled by the availability of ATP as a substrate. In experimental heart failure in large animals, normal or reduced creatine phosphate levels (in most cases together with normal adenine nucleotides) have been described. Reduced creatine phosphate is found in models with increased oxygen consumption, and creatine phosphate may buffer the ATP pool in these models. In human heart failure due to dilated cardiomyopathy, where resting oxygen consumption per unit mass and lactate extraction are normal in most patients, normal adenine nucleotides, creatine phosphate, and mitochondrial function have been described in the initial studies. These results have been challenged by one study showing decreased ATP levels in dilated cardiomyopathy, correlating with the decrease in ejection fraction. However, only ATP has been measured in this study, whereas total adenine nucleotides may be a more suitable parameter. Recently published results have again demonstrated normal ATP and total adenine nucleotides in human heart failure. In the same patients, significantly decreased myocardial norepinephrine was measured, indicating that metabolic changes had occurred in these hearts, but were independent of adenine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenine nucleotide metabolism and contractile dysfunction in heart failure--biochemical aspects, animal experiments, and human studies. 149 76

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.
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PMID:31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure. 155 77

To investigate the effect of heart failure (HF) on skeletal muscle, gracilis, gastrocnemius, and triceps muscle histochemistry and enzyme activity, gracilis muscle performance, and gracilis muscle 31P magnetic resonance spectroscopy (MRS) metabolic responses to exercise were compared in six sham-operated control dogs (C) and seven dogs with HF produced by 3 mo of rapid ventricular pacing. HF reduced skeletal muscle weights and decreased type II fiber area (3,315 +/- 996 to 1,750 +/- 638 microns 2; P less than 0.01). Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activity also tended to decrease. Gracilis muscle inorganic phosphate-to-phosphocreatine ratios, oxygen uptake (VO2), and pH responses to exercise using supramaximal twitch stimulation, a form of exercise that produces maximal stimulation of all muscle fibers and therefore is independent of muscle mass, were similar in both groups. There was no significant difference in developed tension per gram muscle during stimulation at 0.5-200 Hz, maximal developed tension (C: 177 +/- 32 vs. HF: 173 +/- 44 g/g muscle), or muscle fatigability as assessed by percent of initial tension observed at the end of 2 min of 20 Hz stimulation (C: 52 +/- 17% vs. HF: 52 +/- 11%; all P = NS). These data suggest that HF produces skeletal muscle atrophy but that the remaining muscle exhibits normal performance and metabolism.
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PMID:Effect of heart failure on skeletal muscle in dogs. 156 18

Administration of FK506 for 15 days at daily doses of 3.2 mg/kg p.o., 10 mg/kg p.o., 0.32 mg/kg i.m., or 1 mg/kg i.m. to heart-allografted rats resulted in a significant prolongation of graft survival time. The best graft acceptance was obtained in the 1 mg/kg i.m. group: all six grafts survived longer than 50 days, and two of them, indefinitely. The 31P nuclear magnetic resonance (NMR) technique was utilized to investigate in vivo the energy metabolism of grafts. The ratios of inorganic phosphate (Pi)/phosphocreatine (PCr) and PCr/ATP were useful parameters for monitoring cardiac insufficiency after transplantation. The mean ratios of Pi/PCr and PCr/ATP in syngeneic grafts were 0.38 +/- 0.11 and 1.88 +/- 0.42, respectively. In the control allografts, a rapid increase in the Pi/PCr ratio and a decrease in the PCr/ATP ratio were found from day 5. During the period of FK506 administration, increased Pi/PCr and decreased PCr/ATP ratios were also observed in all groups. The changes in these ratios were related with FK506 dosage. The results suggest that FK506 has a side-effect on graft metabolism. The metabolism tended to improve upon cessation of the drug in all grafts, but it worsened again in 3-3 1/2 weeks in the rats treated with 3.2 mg/kg p.o., 10 mg/kg p.o., or 0.32 mg/kg i.m. This seemed to be due to graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo 31P nuclear magnetic resonance findings on heterotopically allografted hearts in rats treated with a novel immunosuppressant, FK506. 169 22

The inotropic effect of a per os single dose of 200 mg disopyramide phosphate was studied in 25 patients during the second week after acute myocardial infarction with no signs of heart failure. Systolic time intervals and the indices derived from the uncalibrated differentiated carotidogram and apexcardiogram were used to assess changes in cardiac performance. The results were as follows: a) Reduction by 3.2% of the haemodynamic ratio LVET/PEP. b) Reduction by 20.1% of the maximal relative upstroke velocity in the differentiated carotidogram (B/S2) p less than 0.05). c) Decrease by 13.1% of the ratio, total amplitude/dicrotic deflection (T/S2) in the same tracing (p less than 0.05). d) Decrease by 2.8% of the ratio, early systolic wave/early diastolic complex wave (b/ef) in the differentiated apexcardiogram. e) Increase by 3.2% of the ratio early diastolic complex total amplitude (ef/ZN) in the previous tracing. The above changes were indicative of a slight negative inotropic effect of the drug.
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PMID:Mechanographic assessment of disopyramide in postinfarction patients. 178 51

Cardiac insufficiency due to chronic ischemic heart disease is accompanied by a reduction of total phosphate at the expense of its organic part with a simultaneous increase of the role of inorganic phosphate during increase of methemoglobin in the erythrocytes. After traditional therapy the methemoglobin level continued to rise while inorganic phosphate and the level of 2,3-DPH decreased. Treatment including myldronate caused an increase of 2,3-DPH in erythrocytes and a decrease of methemoglobin indicating an improvement of the oxygen transport function of the blood.
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PMID:[The phosphate and methemoglobin content of the erythrocytes in patients with ischemic heart disease]. 204 38

Early reports have attributed cardiac failure during acute and chronic models of shock to peripheral vascular dysfunction and decreased venous return. More recently interest has focused on the heart as a primary target responsible for cardiovascular changes associated with acute endotoxin or hemorrhagic shock. At present, it remains controversial whether the heart fails early following the induction of experimental hypodynamic shock. Data from our laboratory have shown that myocardial contractility was increased early following acute endotoxin and splanchnic artery occlusion shock, and it was not until the agonal or terminal phase that contractility was depressed. We have used the slope of the left ventricular pressure-dimension relationship (Ees) as our index of contractile function. This technique is preferential since it is not affected by changes in the loading conditions on the heart. Unlike most reports that have used LV dP/dt as an index of contractility in the intact animal, we have shown that Ees and LV dP/dt do not uniformly reflect changes in contractility. LV dP/dt and related measures do, however, reflect the overall global changes in myocardial performance, which are affected by changes in preload, afterload, heart rate, and contractility. The reductions in LV dP/dt therefore mainly reflect the changes in arterial blood pressure associated with acute hypodynamic shock. The increase in contractility reported during endotoxin shock were shown to be induced by stimulation of beta-adrenergic receptors--when the beta-blocking drug, propranolol, was given to animals during shock, contractility decreased. The mechanism(s) responsible for the failure of the heart during the late or agonal periods of shock is (are) unknown. We have shown in dogs who die as a result of endotoxin shock that the hearts exhibit a progressive energy deficit, whereas animals surviving the experimental protocol maintained levels of ATP and creatine phosphate. It is unclear if the changes in high-energy phosphates during endotoxin shock cause irreversibility. Other potential mediators of cardiac failure have included ischemia/hypoxia, toxic myocardial depressant factors, deterioration of sympathetic influences on the heart, electrophysiologic and ionic disturbances, etc. The relationship between these factors and failure of the heart in vivo during various shock paradigms remains to be elucidated.
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PMID:When does the heart fail during shock? 213 82

To address the hypothesis that impaired ATP synthesis rates caused by changes in the creatine kinase system is an important mechanism underlying cardiac failure, we measured total creatine kinase activity, isoenzyme composition and creatine content in two animal models of hypertrophy with cardiac dysfunction, the spontaneously hypertensive rat in the transition to failure and the creatine-depleted hyperthyroid rat heart challenged by hypoxia. During the transition from stable compensated hypertrophy to failure characterized by decreased functional capacity, we found that total creatine kinase activity and particularly mitochondrial creatine kinase activity decreased. The decrease in functional capacity, the further increase in heart size and the derangements in the creatine kinase system did not occur if these animals were treated for 6 months with the antihypertensive agents, guanethidine or hydralazine. These results suggest that changes in the creatine kinase system occur coordinately with the transition to failure. To assess whether the changes in the creatine system may be causally linked to decreased functional capacity, we used 31P NMR spectroscopy of isolated perfused hearts to define the high energy phosphate content and cardiac performance of creatine-depleted (approximately 50%) hypertrophied hearts challenged by hypoxia. These hearts displayed greater susceptibility to hypoxic injury with regard to both systolic and diastolic function during and following hypoxia. We also measured total creatine kinase activity in right ventricular biopsy specimens from patients with various forms of cardiomyopathy and low ejection fractions, and found a positive correlation between total creatine kinase activity and ejection fraction. Taken together, these results support the hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure.
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PMID:Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. 214 77


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