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)

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (Pi), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.2, 0.4, and 0.6 W). In both groups linear relationships were noted between power output and Pi/PCr; the slope of this relationship was used to compare PCr depletion patterns. At rest both groups had similar Pi/PCr ratios (normal subjects 0.12 +/- 0.06, those with heart failure 0.15 +/- 0.03) and pH (normal subjects 7.04 +/- 0.13, those with heart failure 7.10 +/- 0.11). In normal subjects exercise resulted in a progressive increase in Pi/PCr (slope = 1.17 +/- 0.20 Pi/PCr units/W), a reduction in pH only at 0.6 W (0.2 W: 7.03 +/- 0.10, 0.4 W: 7.01 +/- 0.10, 0.6 W: 6.88 +/- 16) and moderate fatigue (0.2 W: 0 +/- 0, 0.4 W: 1.3 +/- 0.5, 0.6 W: 1.9 +/- 0.6). In patients with heart failure exercise resulted in significantly greater fatigue at all workloads (0.2 W: 1.0 +/- 0.5, 0.4 W: 1.9 +/- 0.6, 0.6 W: 2.9 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance. 396 22

A child with triose phosphate isomerase deficiency has congenital nonspherocytic hemolytic anemia, mental subnormality, motor impairment, growth failure, and cardiac failure. The deficiency state is characterized by moderately reduced red cell triose phosphate isomerase activity and marked instability of the abnormal enzyme to heat. The stability characteristics of triose phosphate isomerase in cultured fibroblasts define the homozygous and heterozygous states with sufficient precision to allow prenatal diagnosis of the disorder. Successful prenatal identification of a heterozygote and an unaffected fetus in utero is described.
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PMID:Triose phosphate isomerase deficiency: prenatal diagnosis. 397 79

Prolonged postischemic ventricular dysfunction ("stunned myocardium") may be responsible for heart failure after myocardial reperfusion. Although inotropic stimulation can enhance the contractility of stunned myocardium, it could potentially increase infarct size and thereby impair ultimate recovery of myocardial function. In 16 anesthetized dogs, the left anterior descending coronary artery was occluded for 2 hours, and then reperfused. At 45 minutes of reperfusion, the dogs were randomized to receive a 3 hour intravenous infusion of either saline solution or dopamine (10 micrograms/kg per min), and 1 hour after the infusion was discontinued the area of necrosis and an in vivo area at risk of necrosis were determined. All dogs had serial two-dimensional echocardiograms with computer-assisted analysis and in vivo biopsies for determination of adenosine triphosphate and creatine phosphate levels. Dopamine caused an increase in the contractility of the reperfused myocardium, with systolic wall thickening increasing from -4.1 +/- 2.6 (mean +/- SEM) to +24.0 +/- 3.7% (p less than 0.002) and short-axis cross-sectional ejection fraction increasing from 27.1 +/- 4.7 to 71.6 +/- 4.4% (p less than 0.002) after 15 minutes of infusion. Regional myocardial blood flow in the previously ischemic epicardium was increased from 1.18 +/- 0.11 ml/min per g with saline to 2.95 +/- 0.36 ml/min per g with dopamine (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inotropic stimulation of reperfused myocardium with dopamine: effects on infarct size and myocardial function. 404 27

473 patients with suspected acute myocardial infarction were entered into a randomised, double-blind, placebo-controlled comparison of disopyramide phosphate, 150 mg three times a day, and oxprenolol, 40 mg three times a day. When analysed on an intension-to-treat basis there was no significant difference in 6-week mortality between the groups, but patients who were able to continue on the active medications fared better than the patients who had to be withdrawn. The withdrawal rate because of heart failure in patients randomised to receive disopyramide was significantly increased. Patients receiving this agent also showed a reduced number of arrhythmic episodes on 24-h tape recordings but this trend did not achieve statistical significance. The results show that the early use of either oxprenolol or disopyramide phosphate in patients with suspected acute myocardial infarction is unlikely to improve mortality.
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PMID:Randomised placebo-controlled trial comparing oxprenolol with disopyramide phosphate in immediate treatment of suspected myocardial infarction. 610 52

The value of beta-blockade and of disopyramide phosphate in the immediate treatment of patients with suspected acute myocardial infarction was assessed in two placebo controlled trials. In the first study 388 patients with suspected acute myocardial infarction were randomly allocated to treatment with propranolol, atenolol, or placebo, and when analysed on an initial intention to treat basis there was no significant difference between the three groups in respect of the mortality at one year. In addition, there was no evidence to suggest that either atenolol, or propranolol reduced the incidence of 'serious' ventricular arrhythmias in the coronary care unit. In the second study 473 patients with suspected acute myocardial infarction were randomly allocated to treatment with oxprenolol, disopyramide phosphate, or placebo. Again no significant differences were seen with respect to the mortality at six weeks. There was, however, a significantly increased incidence of heart failure in the group which received disopyramide phosphate. Patients who received this drug also showed a reduced number of dysrhythmic episodes on 24-hour ECG recordings, but this trend did not achieve statistical significance. These results suggest that none of the three beta-blockers tested nor disopyramide phosphate is likely to reduce the mortality from acute myocardial infarction when given prophylactically, although disopyramide phosphate does reduce the incidence of 'serious' ventriicular arrhythmias.
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PMID:Acute intervention studies in patients with myocardial infarction using atenolol, propranolol, oxprenolol and disopyramide phosphate. 611 75

The effect of several phenothiazines on the extent of cellular damage resulting from the calcium paradox was examined. Hearts treated with trifluoperazine, a potent calmodulin inhibitor, exhibited less cellular damage than untreated myocardium as reflected by light microscopy, high-energy phosphate content and the loss of protein and creatine phosphokinase into the perfusate. A dose response of this effect revealed a maximal response at about 1 microM trifluoperazine, a concentration which lies well within the range generally attributed to calmodulin inhibition. Several other lines of evidence were also obtained suggesting a possible role for calmodulin in calcium-overload induced necrosis. First, the phenothiazines had little influence on membrane changes believed responsible for altered calcium permeability. Second, trifluoperazine was without major effect unless included in the reperfusion buffer, indicating that the drug is only effective during the phase associated with calcium overload. Finally, less protection was afforded hearts exposed to phenothiazines such as chlorpromazine and promethazine, which are weaker inhibitors of calmodulin, than those treated with the potent inhibitor trifluoperazine. While other interpretations are possible, these studies are consistent with a role for calmodulin in calcium overload-induced heart failure.
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PMID:Phenothiazine protection in calcium overload-induced heart failure: a possible role for calmodulin. 613 9

Trabecular preparations from the hog heart right ventricle were "skinned" by treatment with Lubrol WX and glycerol. Ca++ activated isometric contractions were gradedly relaxed by inorganic phosphate (Pi) in the millimolar range or vanadate (Vi) in the micromolar range while tension cost (ATP split/force generated) was increased by a factor of 1.75. From measurements of force, ATPase activity, immediate stiffness and stretch activation, evidence is provided that the mechanical deactivation and the increase in tension cost may result from an acceleration of the myosin cross-bridge cycle, due to a direct interference of Pi and Vi with the chemomechanical energy transformation at the contractile proteins. The possible significance of such a mechanism in cardiac failure or muscle fatigue is discussed.
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PMID:Phosphate and vanadate reduce the efficiency of the chemo-mechanical energy transformation in cardiac muscle. 621 26

VIP containing nerves are present in the kidney and plasma VIP levels are elevated in cardiac failure and severe liver disease. We studied the effects of intravenous VIP; 6 pmol kg-1 min-1 on 6 normal subjects and 3 patients with liver disease. In normal subjects VIP produced flushing and significant rises in heart rate and pulse pressure but the clearance rates of paraaminohippurate and creatinine did not change significantly. Urine flow fell to about 1/3 and the rate of excretion of electrolytes (except phosphate) fell to about a half of control values. Plasma renin activity rose about 3-fold and there were significant rises in haematocrit and the plasma concentrations of solids, calcium and phosphate. The patients with liver disease responded similarly. Elevated plasma VIP could contribute to salt and water retention in disease states.
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PMID:Renal function during vasoactive intestinal peptide (VIP) infusions in normal man and patients with liver disease. 638 98

Three metabolic adaptive or compensatory mechanisms of heart failure were discussed: Adaptation of energy production and of energy availability in the myocardial cell. With increased myocardial oxygen demands this is achieved by a progressive displacement of the mass action ratio of the creatine phosphokinase reaction, so that pronounced changes in the creatine phosphate-ratio, related to myocardial oxygen consumption, are accompanied by only small changes in adenosine-5'-triphosphate adenosine-5'-diphosphate and hence in free energy of the adenine-nucleotide system. Adjustment of the oxygen availability by adaptation of the hemoglobin dissociation curve due to an increase in the erythrocyte content of 2, 3-diphosphoglycerate. This is accompanied by a swelling of erythrocytes as a consequence of an increase in the Gibbs-Donnan potential. In patients with congestive heart failure 2,3-diphosphoglycerate-synthesis is augmented due to respiratory alkalosis and increased concentrations of deoxygenated hemoglobin. Increase in the sympathetic drive of the heart due to increased net discharge of the neurotransmitter caused by reduced neuronal reuptake of norepinephrine. The diminished myocardial norepinephrine content in heart failure is due to the diminished neuronal uptake and to insufficient de novo catecholamine synthesis in the heart. Rather than tyrosine-hydroxylase the transformation of dopamine to norepinephrine seems to be the rate limiting step for catecholamine synthesis in heart failure.
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PMID:Metabolic aspects of compensatory mechanisms in cardiac failure. 651 Jun 22

The following studies were carried out to examine energy metabolites and cardiac performance of the failing heart (hereditary cardiomyopathy) of the Syrian hamster (strain UM-X7.1) perfused either by normal or stress conditions, and to determine whether cyclical changes in energy-related metabolites occurred in the glucose-perfused hearts of both normal and heart failure animals. Hamster hearts from 250-day-old animals with moderate heart failure were removed and perfused either as nonworking hearts (Langendorff method, an afterload pressure of 90 mm Hg and 2.5 mM calcium in the perfusate) or as working hearts with stress conditions [an afterload of 110 mm Hg, high calcium concentrations in the perfusate (3.5 mM), and 10(-8) M isoproterenol]. Mechanical parameters (developed pressure and max dP/dt) and measurements of oxygen consumption indicated that both contractility and oxygen consumption had fallen 50% in myopathic hearts, compared with those of normal hamsters perfused with either of the two conditions. By means of a specially designed stimulator-triggered freeze clamp, hearts were terminated at systole and diastole, and tissue content of ATP, ADP, AMP, adenosine, phosphocreatine, creatine, pyruvate, lactate, and inorganic phosphate were analyzed. A 50% reduction in cardiac performance of the cardiomyopathic hamster hearts was associated with a corresponding reduction in systolic ATP, adenosine, and phosphocreatine values, while inorganic phosphate and lactate increased. With glucose as the sole substrate, the high energy phosphates, ATP and phosphocreatine, reached maximum values during diastole and minimum values during systole.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy levels at systole vs. diastole in normal hamster hearts vs. myopathic hamster hearts. 664 Aug 62


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