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)

The ADP-ATP carrier of the inner mitochondrial membrane is an autoantigen in myocarditis and dilated cardiomyopathy. Sera of patients with these diseases contain carrier-specific autoantibodies that inhibit the transmembrane nucleotide transport on isolated mitochondria. Guinea pigs immunized with the isolated ADP-ATP carrier protein also generate specific carrier-inactivating antibodies. In this study, we measured the cardiac function of guinea pigs immunized with the ADP-ATP carrier by determining the external heart work (EHW) of their isolated perfused spontaneously beating hearts stimulated by 4.0 mmol/L calcium and aortic ligature. Further, the electrogenic transport activity of the ADP-ATP carrier was estimated by calculating the cytosolic-mitochondrial difference of the phosphorylation potential of ATP [delta G(cyt-mit)] in the freeze-clamped isolated hearts by nonaqueous fractionation. The EHW of immunized guinea pigs was seen to be reduced by 54% (P < .005) compared with nonimmunized control guinea pigs, and delta G(cyt-mit) declined from 4.9 kJ/mol ATP in nonimmunized control hearts to 2.3 kJ/mol ATP in the hearts of the immunized guinea pigs (P < .005). The decisive result of this study, however, is the close relation observed between the magnitude of reduction of delta G(cyt-mit) and the size of the decrease in EHW (r = .87). Therefore, it seems plausible that antibody-mediated carrier dysfunction (creating the observed imbalance in myocardial energy metabolism) is responsible for the impairment of cardiac function. Our data support the hypothesis that immunopathic mechanisms in myocarditis and dilated cardiomyopathy can trigger subsequent heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antibody-mediated imbalance of myocardial energy metabolism. A causal factor of cardiac failure? 800 Dec 79

The mechanism whereby chronic rapid ventricular pacing induces severe heart failure is unclear, but the phenomenon is associated with a reduction in left ventricular ATP levels. Accordingly, the current study was undertaken to evaluate the acute effects of rapid ventricular pacing on hemodynamics, left ventricular adenine nucleotide levels, myocardial blood flow, and oxygen consumption. Anesthetized dogs (n = 7) were studied in sinus rhythm and during 30 min of pacing at 250 beats/min. Pacing caused a significant (means +/- SD, all p < 0.001) decrease in cardiac output (3.0 +/- 0.6 to 2.0 +/- 0.6 L/min) and peak left ventricular systolic pressure (133 +/- 14 to 82 +/- 10 mmHg (1 mmHg = 133.3 Pa)) and an increase in pulmonary wedge pressure (10 +/- 2 to 18 +/- 3 mmHg). Following pacing, the peak first derivative of left ventricular pressure and the relaxation time constant, tau, remained unchanged compared with baseline values. Myocardial blood flow and oxygen consumption both increased by 70% with pacing. The transmural distribution of myocardial blood flow and myocardial lactate consumption remained unchanged. There was no change in left ventricular ATP or ADP levels with the observed increase in myocardial oxygen consumption. Therefore, the hemodynamic deterioration associated with acute rapid ventricular pacing, in contrast to that of chronic pacing, is not associated with perturbed myocardial energetics.
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PMID:Myocardial energetics and blood flow in acute rapid ventricular pacing. 801

Using 31P-magnetic resonance spectroscopy during and after exercise, we studied whether forearm metabolic responses to exercise were improved by 1 mo of training in 10 males with heart failure. In the control (untrained) arm, there were no changes in any of the measured variables. In the trained arm, maximal voluntary contraction increased 6% (P = 0.05). During incremental exercise, duration increased 19% (P < 0.05) and submaximal responses improved for pH (6.78 +/- 0.13 pretraining vs. 6.85 +/- 0.17 posttraining; P < 0.01) and PCr/(PCr+Pi) (where PCr is phosphocreatine; 0.48 +/- 0.09 pretraining vs. 0.52 +/- 0.07 posttraining; P < 0.01). The PCr resynthesis rate increased by 48% (P < 0.01), and estimated effective maximal rate of mitochondrial ATP synthesis increased by 37% (P < 0.05). Endurance exercise duration increased by 67% (P < 0.01), and submaximal levels of PCr/(PCr+Pi) (P < 0.05) and pH (P = 0.07) improved. The PCr resynthesis rate (P < 0.01) and the effective maximal rate of mitochondrial ATP synthesis (P < 0.05) also improved. These findings document that impaired oxidative capacity of skeletal muscle can be improved by local muscle training in heart failure, which is compatible with the hypothesis that a part of the abnormality present in heart failure may be due to inactivity.
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PMID:Training partially reverses skeletal muscle metabolic abnormalities during exercise in heart failure. 804 34

The metabolism of the skeletal muscles during exercise and recovery was investigated using phosphocreatinine (PCr) and inorganic phosphate (Pi) in patients with chronic heart failure. PCr/Pi ratio, which is closely related to the ATP/ADP ratio, and the pH were measured by 31P-magnetic resonance spectroscopy (31P-MRS) during and after forearm exercise in 9 patients with chronic heart failure, 11 patients with chronic lung disease, and 8 normal subjects. Exercise and recovery scans were recorded every minute for 4 min. The PCr/Pi ratio in patients was lower during the recovery period and significantly lower 3 and 4 min after exercise than in normal subjects. The pH values after exercise were lower in patients, although not significantly. The PCr/Pi ratio 4 min after exercise in patients was not correlated with parameters of cardiac function or arterial and mixed venous oxygen tension. Nutritional parameters did not vary statistically among the groups. Metabolic abnormalities may be present in the skeletal muscles of patients' group, which are not due to undernutrition, possibly as a result of exercise deconditioning and probably a shift in fiber distribution (type I decreases, type IIb increases) and a decrease in oxidative capacity.
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PMID:[Alterations of skeletal muscle metabolism in patients with congestive heart failure]. 804 95

NMR spectroscopy is a powerful and non-invasive technique with which to study cardiac energy metabolism in vivo. This method makes use of the "spin" properties of certain atomic nuclei. The naturally occurring phosphorus nucleus (P-31) is visible by NMR and phosphorus-31 NMR spectra contain signals from the major components of energy metabolism. In vivo, the phosphocreatine to ATP ratio (PCr/ATP) is used as an index of the energy status and viability of the myocardium. However, it is the response of this metabolic index to differing physiological and pharmacological stresses that has helped to elucidate the mechanisms that regulate cellular respiration and to highlight abnormalities in heart failure. As there are many technical difficulties involved with cardiac NMR, 31-phosphorus studies of skeletal muscle have provided an indirect way of studying abnormalities in myocardial metabolism in vivo. One of the unique features of NMR is that it permits in vivo measurements of fluxes through key enzymes in energy metabolism using magnetization transfer. Determination of the rates of energy transfer through the creatine kinase reaction and energy turnover in vivo will provide new insights into the control of energy metabolism in health and disease. Alternatively, carbon-13 NMR can be used to measure fluxes through the different metabolic pathways of synthesis and catabolism following administration of selectively labelled carbon-13 substrates. In conclusion, the non-invasive and versatile nature of NMR spectroscopy makes it an ideal method to assess and evaluate energy metabolism in vivo.
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PMID:Evaluation of myocardial energy status in vivo by NMR spectroscopy. 811 45

Several important questions remain to be answered by future research. First, it is unclear whether any abnormal index of diastolic function can be used to estimate disease severity, or to prognostically identify patients who will subsequently develop systolic abnormalities or frank left ventricular dysfunction. A temporal relationship between the appearance of diastolic dysfunction and ultimate left ventricular decompensation may, theoretically, exist, but such a relationship has yet to be established. Second, a growing body of evidence indicates that pharmacologic therapy with Ca2+ channel antagonists, beta-adrenergic agonists or antagonists, phosphodiesterase inhibitors, or angiotensin converting enzyme inhibitors may acutely or chronically benefit certain patients with diastolic dysfunction. Whether the impact of early recognition and therapeutic intervention in patients with diastolic dysfunction can be translated into an improvement of quality of life or enhanced survival remains unknown. Third, recent evidence indicates that fundamental changes in the biochemistry of the cardiac myocyte may represent a final common pathway for the development of congestive heart failure resulting from intrinsic cardiac disease. Altered expression of genes coding for the ATP-dependent Ca2+ pumps in the sarcolemma and the sarcoplasmic reticulum, regulatory proteins such as phospholamban, and the proteins composing the contractile apparatus have been identified that play critical roles in the pathophysiology of myocardial failure, and have important implications for potential pharmacologic therapy. Future research will more clearly elucidate these cellular and biochemical mechanisms of left ventricular failure. Lastly, although intravenous and inhalational anesthetics produce derangements in normal diastolic function to varying degrees, whether the effects of these agents on diastolic performance are exacerbated in disease processes manifested by abnormal diastolic mechanisms requires further evaluation.
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PMID:Left ventricular diastolic function in the normal and diseased heart. Perspectives for the anesthesiologist (2). 823 87

The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs.
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PMID:Role of metabolic therapy in cardiovascular disease. 824 95

Digitalis, diuretics, and vasodilators are considered standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure, which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2500 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing drug surveillance study in 173 Italian centers. The daily dose of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two- to seven-point scales. Preliminary results on 1113 patients (mean age 69.5 years) show a low incidence of side effects: 10 adverse reactions were reported in 8 (0.8%) patients, of which only 5 reactions were considered as correlated to the test treatment. After 3 months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 81%, edema 76.9%, pulmonary rales 78.4%, enlargement of the liver area 49.3%, jugular reflux 81.5%, dyspnea 54.2%, palpitations 75.7%, sweating 82.4%, arrhythmia 62%, insomnia 60.2%, vertigo 73%, and nocturia 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators. 824

To elucidate the relationship between functional alterations and disturbances in myocardial energy metabolism of rats with heart failure following coronary artery ligation, the left coronary artery of the rat was ligated and the time course of changes in cardiac function and myocardial energy state of the animal were examined for 12 weeks after the ligation. Coronary artery ligation resulted in approximately 40% infarction of the left ventricle, an increase in the right ventricular weight, a decrease in left ventricular developed pressure, an increase in left ventricular end-diastolic pressure throughout the experiment, suggesting the development of cardiac failure after the operation. Cardiac output and stroke volume indices were not altered during the first 4 weeks, but were significantly decreased on the 8th and 12th weeks, suggesting that cardiac function had further aggravated by 8 weeks after the operation. Myocardial energy profiles of the scar tissue, the remaining left ventricle and interseptum, and the right ventricle were determined. Tissue ATP (27.54 +/- 0.82 to 26.38 +/- 1.58 mumol/g dry tissue; n = 8-10) and creatine phosphate (26.73 +/- 1.63 to 24.38 +/- 1.83 mumol/g dry tissue; n = 8-10) of the remaining viable left ventricle were lower than control (33.17 +/- 0.73 and 40.04 +/- 1.07 mumol/g dry tissue; n = 8) throughout the experiment. A marked decrease in tissue ATP and CP was seen in the scar tissue throughout the experiment. Increases in tissue lactate of the remaining left ventricle and the right ventricle were detected from 1 to 2 weeks after the operation, but returned to the control levels thereafter. Mitochondrial oxygen consumption rates of isolated myocardial bundles from the 8th and 12th weeks (21.03 +/- 2.22 and 17.79 +/- 3.24 ng oxygen/min/mg dry tissue; n = 8) were lower than control (33.15 +/- 1.95 ng oxygen/min/mg dry tissue; n = 5), and those of the interseptum (23.71 +/- 1.33 ng oxygen/min/mg dry tissue; n = 8) and the right ventricle (22.44 +/- 2.73 ng oxygen/min/mg dry tissue; n = 8) on the 12th week after the operation were lower than control (33.58 +/- 2.80 and 34.83 +/- 2.64 ng oxygen/min/mg dry tissue; n = 5). The results provide evidence for a decline in myocardial energy store and energy producing ability associated with the development of cardiac failure.
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PMID:Regional energy metabolism of failing hearts following myocardial infarction. 828 76

The initial phase of heart failure is characterized by peripheral mechanisms such as sympathetic stimulation and neuroendocrine activation, which attempt to compensate for the decline in cardiac pump function and tissue underperfusion. However, the resulting vasoconstriction and sodium and water retention lead to a vicious circle wherein the subsequent increase in afterload and in circulating volume eventually leads to a further decline in cardiac output, blood pressure and tissue perfusion on the one hand, and to systemic and pulmonary congestion on the other. Intrinsic cardiac alterations during progressive failure preclude efficient cardiac compensation. These alterations include downregulation of the beta-receptor, upregulation of its inhibitor subunit (Gi), changes in adenylate cyclase and phosphodiesterase activity, depletion of catecholamine stores, overexpression of abnormal contractile proteins and inherent changes in ATP-ase activity, a derangement of calcium cycling by the sarcoplasmic reticulum, and abnormalities in myocardial energy production and transfer. These multiple changes underline the importance of the heart per se in heart failure. However, it should be realized that the heart failure syndrome depends to a large extent on various intrinsic alterations in peripheral tissue function. Renal impairment, baroreceptor dysfunction, neuroendocrine activation, abnormalities in skeletal muscle metabolism and in vascular control, and electrolyte disturbances all add to the overall clinical picture. Both cardiac and peripheral alterations in heart failure will markedly affect future diagnostic and therapeutic approaches to this syndrome.
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PMID:Pathophysiology and therapy of heart failure, new insights and developments. Part II. Cardiac and peripheral alterations during progressive heart failure. 830 92


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