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)

To identify any differences in inhibitory G protein (Gi) attributable to species or the cause of heart failure, we studied the changes in this protein in different animal models of heart failure: 1) different species; rats vs. hamsters (F1B) with cardiomyopathy induced by adriamycin (ADR) and 2) different etiologies; rats with ischemic heart failure (IHD) due to coronary artery ligation vs. rats with cardiomyopathy induced by ADR and F1B (20-week-old) hamsters with cardiomyopathy induced by ADR vs Syrian hamsters BIO 14.6 (40-week-old) with genetic cardiomyopathy, using Western blotting methods and ADP-ribosylation. We also sought to determine whether changes in the amount of Gi protein reflected the regulation of adenylate cyclase. The amount of immunodetectable Gi rose by 35% (p < 0.05) in ADR rats, 25% (p < 0.05) in ADR hamsters, 15% (p < 0.05) in IHD rats, and 28% (p < 0.05) in BIO 14.6 hamsters, as compared with control rats, F1B (20-week-old) hamsters, sham-operated control rats, and F1B (40-week-old) hamsters, respectively. Assessment of Gi by pertussis toxin-catalyzed ADP-ribosylation revealed increases in Gi of 24% (p < 0.05) in ADR rats and of 44% (p < 0.05) in BIO 14.6 hamsters, as compared with their respective controls. Gi function, as assayed by the acetylcholine-induced inhibition of adenylate cyclase, also increased. Thus, Gi protein appears to contribute to the changes in signal transduction in myocardium with heart failure.
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PMID:Increased levels of inhibitory G protein in myocardium with heart failure. 769 38

The endothelium is critically involved in the regulation of vascular function through its barrier role, via interaction with circulating cells such as platelets, which then release vasoactive or growth regulating agents, through production of substances which may modulate vascular tone and smooth muscle cell growth and also exert anti-thrombotic effects. The release of serotonin, adenosine diphosphate (ADP), or growth factors from platelets adhering to damaged endothelium, the release of endothelium-derived relaxing or contracting factors (nitric oxide, prostanoids, endothelin), the production of growth factors, all of which exert their effects in paracrine or even autocrine fashion, are some of the mechanisms whereby the endothelium influences vascular tone and growth and platelet aggregation. In different conditions such as hypertension, atherosclerosis, diabetes, heart failure, ischemic heart disease, sepsis, and shock, dysfunction of the endothelium plays an important pathophysiological role through reduction or enhancement of the release of these different products with significant hemodynamic and trophic effects. Therapeutic interventions targeting the endothelium hold promise in the treatment and prevention of some cardiovascular diseases and their complications.
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PMID:The endothelium and control of blood vessel function in health and disease. 789 24

In order to explain the attenuated sympathetic support during the development of heart failure, the status of beta-adrenergic mechanisms in the failing myocardium was assessed by employing cardiomyopathic hamsters (155-170 days old) at moderate degree of congestive heart failure. The norepinephrine turnover rate was increased but the norepinephrine content was decreased in cardiomyopathic hearts. The number and the affinity of beta receptors in the sarcolemmal preparations were not changed in these hearts at moderate stage of congestive heart failure. While the basal adenylyl cyclase activity was not altered in sarcolemma, the stimulation of enzyme activity by NaF, forskolin, Gpp(NH)p or epinephrine was depressed in hearts from these cardiomyopathic hamsters. Since G-proteins are involved in modifying the adenylyl cyclase activity, the functional and bioactivities as well as contents of both Gs and Gi proteins were determined in the cardiomyopathic heart sarcolemma. The functional stimulation of adenylyl cyclase by cholera toxin, which activates Gs proteins, was markedly depressed whereas that by Pertussis toxin, which inhibits Gi proteins, was markedly augmented in cardiomyopathic hearts. The cholera toxin and pertussis toxin catalyzed ADP-ribosylation was increased by 37 and 126%, respectively; this indicated increased bioactivities of both Gs and Gi proteins in experimental preparations. The immunoblot analysis suggested 74 and 124% increase in Gs and Gi contents in failing hearts, respectively. These results suggest that depressed adenylyl cyclase activation in cardiomyopathic hamsters may not only be due to increased content and bioactivity of Gi proteins but the functional uncoupling of Gs proteins from the adenylyl cyclase enzyme may also be involved at this stage of heart failure.
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PMID:Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters. 789 87

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.
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PMID:Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study. 794 49

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

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

Platelet function, antithrombin and plasminogen activities, and fibrinolytic capabilities in 11 cats with acquired heart disease were compared with results in 4 healthy cats. Of 11 cats with heart disease, 9 had hyperthyroidism with secondary cardiac dysfunction. One cat with hyperthyroidism had renal disease and heart failure, and of 2 cats with idiopathic hypertrophic cardiomyopathy, 1 also had renal disease. At the time of testing, 3 cats had thromboembolic events associated with the disease. Compared with healthy cats, cats with acquired heart disease had increased activity of antithrombin III, a protein that behaves as an acute-phase reactant. Plasminogen activity was decreased, although not significantly, in cats with acquired heart disease, compared with results in healthy cats. In cats with left ventricular dysfunction, clot retraction was decreased (marginal significance, P = 0.058) and might be attributed, in some cases, to the medications received by the cats. Dilute whole blood clots from all cats failed to lyse in vitro. This observation, at present, lacks adequate explanation. Platelets from cats with acquired heart disease, compared with platelets from healthy cats, had decreased responsiveness (aggregation and [14C]serotonin release) to adenosine diphosphate and increased responsiveness to collagen. Hyperthyroid cats were receiving various drugs (propranolol, atenolol, or diltiazem) to empirically treat clinical signs of disease attributable to cardiac dysfunction. Although numbers of cats in each group were small, definite trends were observed in the results of tests. Platelets from cats receiving atenolol had decreased responsiveness to adenosine diphosphate and unaltered responsiveness to collagen, compared with platelets from healthy cats, and may have decreased risk of thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease. 806 8

The role of the beta-adrenoceptor-G-protein-adenylate cyclase system in the pathogenesis of cardiac hypertrophy was studied. We have used a minipig model of pressure-overload cardiac hypertrophy secondary to aortic banding. Four groups of five animals were used: minipigs made hypertrophic were evaluated 2 months (CH2 group) and 9 months (CH9 group) later and compared to controls (C2 and C9 groups, respectively). A decrease in beta-adrenergic receptor density and an increase in antagonist affinity were shown in left ventricular membranes of hypertrophied animals compared with controls. In both groups, CH2 and CH9, an increase in EC50 for isoproterenol-stimulated adenylate cyclase activity, an increase in forskolin-stimulated adenylate cyclase activity and a diminished inhibition by carbachol of isoproterenol-stimulated adenylate cyclase were observed. In contrast, fluoride-stimulated adenylate cyclase activity was markedly increased only in the end stage of hypertrophy. alpha s-cholera toxin-catalysed ADP-ribosylation is increased in early hypertrophy and then decreases with late hypertrophy and a similar pattern is observed with alpha o pertussis toxin-catalysed ADP-ribosylation, whereas alpha i-ADP-ribosylation remains unchanged. Tissue content of Gs-, Gi- and Go-proteins, as assessed by specific antibodies, was found unchanged in CH9 and CH2 groups when compared with that in C9 and C2 control groups, respectively. Modifications in Gs functional activity in later hypertrophic stages, expressed as alterations in cholera toxin ADP-ribosylation and adenylate cyclase fluoride responsiveness, may be important in the pathogenesis of decompensation from compensated hypertrophy to cardiac failure.
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PMID:Cardiac beta-adrenoceptors, G-proteins and adenylate cyclase regulation during myocardial hypertrophy. 838 1

Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.
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PMID:O2 uptake kinetics in response to exercise. A measure of tissue anaerobiosis in heart failure. 844 60


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