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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a pertussis epidemic, the majority of children admitted with respiratory disease were under one year old and had pneumonia, with or without pertussis syndrome; heart failure was common. A greater proportion of those with 'pneumonia alone' were slightly older, were malnourished, were admitted earlier and recovered slightly faster than those who had 'pertussis with pneumonia'. Differential white cell count was of little help in diagnosis and chest X-ray findings seldom altered management. Eight percent of the pertussis and 3 percent of the pneumonia groups died: all had pneumonia and additional complications, and 71 percent of those who died were under one year of age. Results suggest that two or more infections of triple antigen may protect some children from an attack of pertussis so severe that hospital care would be needed.
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PMID:Childhood pertussis and pneumonia admissions in the highlands of Papua New Guinea. 27 31

A 21 month-old unvaccinated boy was admitted for an acute respiratory distress episode associated with major leukocytosis (maximum = 146 G/l). Transient heart failure and pneumomediastinum occurred but the outcome was favourable. Coughing attacks then occurred and the diagnosis of pertussis was serologically confirmed. This case report is reminiscent of the possible severity of pertussis pneumoniae, the mechanisms of haematologic abnormalities, and stresses to the benefit of pertussis vaccination.
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PMID:[Diffuse alveolar pertussis with major hyperleukocytosis with "pseudocentrocytic" contingent]. 131 26

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.
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PMID:Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension. 131 58

1. A decreased responsiveness to the positive inotropic effects of beta-adrenoceptor agonists is a characteristic of human heart failure. We have investigated the involvement of inhibitory guanine nucleotide binding proteins (G-proteins) in this process using pertussis toxin treatment of isolated cardiac myocytes. 2. Myocytes isolated from failing human myocardium had a reduced maximum contractile response to isoprenaline relative to that for maximally stimulating concentrations of calcium, giving an isoprenaline/calcium ratio of 0.71 +/- 0.06 (n = 7 patients). This was significantly lower than in myocytes from non-failing myocardium, where the isoprenaline/calcium ratio was 1.16 +/- 0.07 (n = 6, P less than 0.001). Responses to high calcium were unchanged. 3. Myocytes were treated with pertussis toxin for 3-5 h at 35 degrees C. Successful inactivation of inhibitory G-proteins by pertussis toxin treatment was indicated by a loss of responsiveness to 10 microM adenosine (in the presence of submaximal isoprenaline). 4. Following pertussis toxin treatment of the myocytes from failing human heart the isoprenaline/calcium ratio increased to 1.43 +/- 0.27 (n = 7, P less than 0.05). Pertussis toxin treatment had no effect upon the maximum calcium contraction. The isoprenaline/calcium ratio in myocytes from non-failing human ventricle was not affected by the toxin treatment (n = 3). These observations support the hypothesis that increased inhibitory G-protein levels or activities contribute to beta-adrenoceptor desensitization in human heart failure. 5. beta-Adrenoceptor desensitization in human heart failure is thought to be secondary to raised noradrenaline levels in these patients. Experiments were repeated on myocytes isolated from hearts of guinea-pigs which had been chronically infused with noradrenaline. The isoprenaline/calcium ratio of these myocytes was reduced below that of myocytes from sham-operated animals (0.65 0.04, n = 6 compared with 0.88 +/- 0.02, n = 7, P<0.001).6. Pertussis toxin treatment (2 h at 35 degrees C) increased the isoprenaline/calcium ratio to 1.02 0.02 (n = 6,P<0.01) in myocytes from noradrenaline-treated guinea-pigs. This effect of pertussis toxin treatment was not seen in myocytes from sham-operated guinea-pig hearts.7. Incubation at 35 degrees C for similar periods in the absence of pertussis toxin also restored the isoprenaline/calcium ratio towards normal in the myocytes from both failing human and noradrenaline-treated guinea-pig hearts, although the effect was significantly smaller than that produced by the toxin. Myocytes kept at room temperature (22 degrees C) showed no such evidence of resensitization over periods up to 6h.8. These observations are consistent with the hypothesis that raised catecholamine levels result in increased inhibitory G-protein levels and functional P-adrenoceptor desensitization in heart failure.
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PMID:The effect of pertussis toxin on beta-adrenoceptor responses in isolated cardiac myocytes from noradrenaline-treated guinea-pigs and patients with cardiac failure. 132 64

Heterotrimeric Gi-proteins play an important role in the regulation of cardiac adenylate cyclase. Besides a downregulation of beta-adrenoceptors with an accompanying reduction of the positive inotropic effects of cAMP-dependent positive inotropic agents, an increase of pertussis toxin substrates (Gi alpha-proteins) has been observed. The increase of Gi alpha has been reported to be associated with a reduced adenylate cyclase activity in dilated cardiomyopathy from hearts with heart failure class NYHA IV. Since the quantification of Gi alpha-proteins with the pertussis toxin labeling method is hampered by a number of biological and technical factors, Gi alpha-proteins were quantified radioimmunologically using the iodinated C-terminus 125I-KENLKDCGLF as tracer, purified retinal transducin alpha as standard, and an antiserum (DS 4) raised against the same peptide. With this technique Gi alpha-proteins were increased by 118% in dilated cardiomyopathy and 48% in ischemic cardiomyopathy, although pertussis toxin substrates were only increased by 40% in dilated cardiomyopathy and no change was observed in ischemic cardiomyopathy. In cardiomyopathic tissue, an inverse relationship was observed between the increase of Gi alpha and the positive inotropic effects of isoprenaline or milrinone. These data provide evidence for a functional role of Gi alpha in the reduced positive inotropic effects of cAMP-dependent positive inotropic agents. In addition, results obtained with pertussis toxin labeling for quantification of Gi alpha-proteins do not necessarily reflect the expression of Gi alpha-proteins in the human myocardium.
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PMID:Quantification of Gi alpha-proteins in the failing and nonfailing human myocardium. 149 77

In human end-stage heart failure an increased amount of inhibitory G-protein alpha-subunits (Gi alpha) is assumed to play a role in desensitization of the adenylyl cyclase signaling pathway. In the present study, northern blot experiments with 32P-labeled cDNA probes in ventricular tissue samples from explanted human hearts revealed that Gi alpha-2- and Gi alpha-3- mRNA are the predominant Gi alpha-mRNA subtypes in human ventricles, whereas Gi alpha-1-mRNA was not detectable. The mRNA for the stimulatory G-protein alpha-subunit (GS alpha) consisted of two mRNA sizes. Quantification of mRNA levels revealed a 103 +/- 38% increase in Gi alpha-2-mRNA levels in hearts with idiopathic dilative cardiomyopathy (IDC; n = 8), and a 77 +/- 25% increase in hearts with ischemic cardiomyopathy (ICM; n = 6) as compared to nonfailing controls (NF, n = 8). In contrast, Gi alpha-3- and GS alpha-mRNA levels were similar in failing and nonfailing hearts. To investigate whether or not the increased expression of Gi alpha-2-mRNA might be due to chronically elevated catecholamine levels, we determined the influence of a 4-day infusion of isoprenaline (Iso; 2.4 mg/kg.d), propranolol (Prop; 9.9 mg/kg.d), Iso + Prop or 0.9% NaCl as control (Ctr) on myocardial Gi alpha-mRNA and Gi alpha-protein levels in rats. In Iso-treated rats, hybridization experiments revealed a 49 +/- 18% (n = 7) and 27 +/- 7% (n = 8) increase in Gi alpha-2 and Gi alpha-3-mRNA, respectively. Pertussis toxin-catalyzed ADP-ribosylation revealed a 22 +/- 7% (n = 8) increase in Gi-protein as compared to Ctr (n = 8). These alterations were accompanied by an increased potency for the negative inotropic effect (NIE) of carbachol (mean EC50: 0.04 microM vs. 0.28 microM) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop itself had no effect, but it antagonized all Iso-induced effects. We conclude that, in human heart failure due to IDC or ICM, increased Gi alpha-2-, but not Gi alpha-3- mRNA levels accompany the increased amount of Gi alpha-protein, suggesting that this increase is at least in part due to increased de novo synthesis. The experiments in rats demonstrated that chronic beta-adrenergic stimulation leads to an increased expression of Gi alpha-mRNA and -protein, and to an enhanced potency of the negative inotropic effect of muscarinic agonists.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation and possible functional implications of G-protein mRNA expression in nonfailing and failing ventricular myocardium. 149 78

Changes in the beta-adrenergic receptor-G protein-adenylate cyclase complex were investigated in an experimental canine model of low-output heart failure produced by chronic rapid ventricular pacing. The contractile response occurring after exposure to the beta-adrenergic agonist dobutamine, measured as peak left ventricular + dP/dt, was decreased after 3 weeks of pacing. To further characterize the diminished functional responsiveness to beta-adrenergic receptor stimulation, beta-adrenergic receptor-adenylate cyclase coupling was investigated using membranes prepared from both control and paced animals. The density of beta-adrenergic receptors was decreased by 40% with a selective downregulation of the beta 1-subtype. The affinity of the receptor for the antagonist radioligand [125I]iodocyanopindolol remained unchanged. A defect in coupling was suggested by a decreased ability of isoproterenol, fluoride, and forskolin to stimulate adenylate cyclase in membranes prepared from failing hearts. Determination of the levels of Gi alpha (the alpha-subunit of Gi) by immunoblotting and pertussis toxin labeling revealed modest increases of approximately 30%. Furthermore, Mn2+ and purified Gs failed to stimulate adenylate cyclase in membranes prepared from failing hearts, indicating an impairment in the catalytic moiety of adenylate cyclase itself or in the ability of adenylate cyclase to couple to Gs. In contrast, complementation assay did not reveal differences in the functional activity of Gs alpha (the alpha-subunit of Gs). Taken together, these data demonstrate a selective decrease in the beta 1-subtype of adrenergic receptors and an increase in a 40-kd G1-like protein in the failing heart. Similar changes have been described in human idiopathic dilated cardiomyopathy. In addition to these changes, we identified a possible defect at the level of the catalytic subunit of adenylate cyclase.
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PMID:Beta-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. 165 3

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.
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PMID:Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. 283 45

Prior physiological studies have suggested that parasympathetic control is altered in heart failure. The goal of our studies was to investigate the influence of heart failure on the muscarinic receptor, and its coupling to adenylate cyclase. Ligand binding studies using [3H]quinuclidinyl benzilate and enriched left ventricular (LV) sarcolemma, demonstrated that muscarinic receptor density in heart failure declined 36% from a control of 5.6 +/- 0.6 pmol/mg, with no change in antagonist affinity. However, agonist competition studies with both carbachol and oxotremorine showed that it was a loss of high affinity agonist binding sites in the sarcolemma from failing LV that accounted for this difference. The functional efficacy of the muscarinic receptor was also examined. When 1 microM methacholine was added to 0.1 mM GTP and 0.1 mM isoproterenol, adenylate cyclase stimulated activity was inhibited by 15% in normal LV but only 5% in LV sarcolemma from animals with heart failure even when the reduced adenylate cyclase in these heart failure animals was taken into account. Even at 100-fold greater concentrations of methacholine, significantly less inhibition of adenylate cyclase activity was observed in LV failure as compared with normal LV sarcolemma. Levels of the GTP-inhibitory protein known to couple the muscarinic receptor to adenylate cyclase, as measured with pertussis toxin labeling, were not depressed in LV failure. Thus, the inhibitory pathway regulating LV adenylate cyclase activity is defective in heart failure. The decrease in muscarinic receptor density, and in particular the specific loss of the high affinity agonist binding component of this receptor population, appears to be the major factor underlying this abnormality.
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PMID:Impaired cardiac muscarinic receptor function in dogs with heart failure. 329 Feb 56

Alterations of receptor-G-protein-regulated adenylyl cyclase activity have been suggested to represent an important alteration leading to contractile dysfunction in the failing human heart. Recent experiments suggest that the beta 1-adrenoceptor (beta 1 AR) density and mRNA levels are reduced, while beta 2-adrenoceptors and stimulatory G-proteins are unchanged (mRNA and protein level). Functional assays demonstrated that the catalyst of the adenylyl cyclase is not different between failing and nonfailing myocardium. Inhibitory G-proteins are increased (pertussis toxin substrates, protein and mRNA) and correlate to the reduced inotropic effects of beta-adrenoceptor agonists and of cAMP-PDE inhibitors. Gi alpha-coupled m-cholinoceptors and A1-adrenergic receptors are unchanged in density and affinity. Stimulation of these receptors resulted in an unchanged antiadrenergic effect on force of contraction. In conclusion, a downregulation of beta 1 AR and an increase of Gi alpha have been observed as signal transduction alteration in failing human myocardium. These alterations are due to alterations of gene expression in the failing heart and are related to a defective regulation of force of contraction in heart failure.
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PMID:Alterations of beta-adrenoceptor-G-protein-regulated adenylyl cyclase in heart failure. 749 44


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