Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial beta-adrenoceptor density. The patients were divided into three groups according to type and severity of CHD: group I consisted of 6 patients with acyanotic shunt lesions of moderate severity; group II comprised 13 children with severe acyanotic shunt and valve lesions and group III included 7 children with cyanotic CHD. The myocardial beta-adrenoceptor density was determined using (-)3-[125I]Iodocyanopindolol [( 125I]ICYP) and was reduced by approximately 50% in severe acyanotic CHD (33.6 fmol/mg protein) and cyanotic CHD (35.3 fmol/mg protein) in comparison with the group with less severe acyanotic shunt defects (64.4 fmol/mg protein). The affinity dissociation constant (Kd.ICYP) did not differ statistically between the groups. The proportion of beta 1- and beta 2-subpopulations was evaluated by ICI 118,551-[125I]ICYP competition studies. In group II (61.5%) and group III (69.1%) significant lower portions of beta 1-adrenoceptors were found compared with group I (78.2%). This shift of subpopulations was due to a decreased beta 1-receptor density while beta 2-receptor density was unchanged in all groups. While the plasma noradrenaline levels of group I were similar to those of a control group of 13 healthy children, respective values of group II and III were significantly elevated. A significant negative correlation was found between plasma noradrenaline levels and myocardial beta-adrenoceptor density. It is concluded that exposure of these receptors to increased circulating catecholamines, due to an enhanced sympathetic tone, leads to a reduction of their density.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial beta-adrenoceptor density and the distribution of beta 1- and beta 2-adrenoceptor subpopulations in children with congenital heart disease. 164 67

Sympathetic regulation of myocardial performance has been shown to be altered in congestive heart failure. Right atrial tissue of children with severe acyanotic and cyanotic congenital heart disease (CHD) showed a significantly lower beta-receptor density than that of children with less severe defects. Since mononuclear leukocytes (MNL) contain a homogeneous population of beta 2-adrenoceptors which have similar properties to those of cardiac beta 2-adrenoceptors, they are frequently used for studying the beta-adrenergic system. In a group of 37 children with CHD of different types and severity who underwent cardiac surgery, we compared the MNL beta-adrenoceptor density to the type and severity of CHD and looked for a possible relationship to plasma catecholamine levels and to the right atrial beta-adrenoceptor density. Membranes of MNL and myocardial cells were radiolabeled with (-)3-[125I]Iodocyanopindolol [( 125I]ICYP). A significantly higher beta-adrenoceptor density on MNL was found in patients with moderate acyanotic CHD (group I) than in those with severe acyanotic (group II) and cyanotic CHD (group III). Patients of group I showed approximately 50% higher myocardial beta-receptor density than those of groups II and III. ICI 118.551-[125I]ICYP competition studies revealed that in groups II and III significantly lower proportions and densities of beta 1-receptors were found compared to group I. Noradrenaline (NA) plasma levels in group II and group III were significantly higher than those in group I. The adrenaline plasma levels were found to be very high in all children with CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenoceptor density on mononuclear leukocytes and right atrial myocardium in infants and children with congenital heart disease. 166 27

Alcohol decreases myocardial contractility through direct, toxic effect. Ingestion of more than 150 g per day for more than 10 years carries a high risk of developing alcoholic cardiomyopathy. The discontinuance of alcohol intake--if put into effect early in the natural history of patients with alcoholic cardiomyopathy--commonly but not invariably results in remission of heart failure. In order to evaluate the left ventricular (LV) function and to find out a possible correlation between the degree of cardiac dysfunction and the severity of the morpho-functional aspects of alcoholic liver disease, 20 chronic alcoholic patients without clinical evidence of heart disease were examined. Echocardiography, systolic time intervals, mechanical polygraphic recordings and liver biopsy were obtained. According to the morphological alterations showed by the needle biopsy of the liver, we separated 12 patients with liver steatosis (Group I) from 8 subjects with alcoholic hepatitis and fibrosis. In Group I LVET, ICT, PEP/LVET indices and LV fractional shortening (delta %) were not statistically different from control subjects. Patients of Group II showed marked impairment of myocardial function, as revealed by significant ICT, PEP, PEP/LVET prolongation and by an equally significant reduction of fractional shortening of the LV. The noninvasive method has proved to be quite useful in detecting early LV dysfunction in asymptomatic chronic alcoholics and has revealed a correlation between the severity of the morphological involvement of the liver and the impairment of cardiac performance.
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PMID:[Non-invasive evaluation of left ventricular function in chronic alcoholics. Histo-morphological and echo-polygraphic correlations]. 718 10

In 103 out of 220 alcoholics (46.8%) with no heart disease electrocardiographic abnormalities were found, sinus tachycardia, T-wave irregularities and intraventricular conduction disturbances being the most common features. Comparing 138 chronic alcoholics with those of 134 healthy abstainers for the systolic time-intervals, the following abnormalities were found in the former group: prolonged PEP and ICT, shortened LVET, increased PEP/LVET and heart rate. Correction of the time intervals for heart-rate left the direction of the changes unaffected. Nor was the age of the subjects found to affect the intervals to any significant degree either in the alcoholics or in the control group. It is therefore assumed that the effect of alcohol on the time-intervals operates through at least two mechanisms, an increase in heart-rate, and a depression of myocardial contractility.
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PMID:Changes in cardiac function in the "preclinical" stage of alcoholic heart disease. 745 29

Estrogen is a key regulatory hormone, which in addition to its role in reproduction, affects a number of physiological systems, including the skeleton and cardiovascular system. The important role of estrogen in various tissues is perhaps most evident in postmenopausal women who, in addition to menopausal symptoms, experience increases in osteoporosis and coronary heart disease as their estrogen levels decline. Estrogen replacement, while effective against osteoporosis and heart disease, produces a number of side effects associated with the breast and uterus which limits compliance. Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, produce beneficial estrogen-like effects on bone and lipid metabolism, while antagonizing estrogen in reproductive tissue. SERMs can be distinguished from each other in reproductive tissue, particularly the uterus, by their activity profile. For example, while triphenylethylenes like tamoxifen behave as partial agonists, raloxifene (a benzothiophene) behaves as a complete antagonist in the uterus. The SERM profile is distinct from that of full estrogens (ie. 17beta-estradiol or 17alpha-dihydroequilenin) which behave as estrogen agonists in all tissues and pure estrogen antagonists (i.e. ICI-164,384) which exhibit only an estrogen antagonist profile in a battery of tissue types. The precise mechanism by which SERMs produce this tissue-selective pharmacology remains a question. It is clear, however, that for raloxifene, both the estrogen agonist effects on bone and cholesterol metabolism as well as the estrogen antagonist effects in uterine and mammary tissue involve high affinity interaction with the estrogen receptor. The estrogen antagonist activity is mediated via classical pharmacological competition for estrogen receptor binding. The estrogen agonist activity, in bone for example, appears to involve novel post-receptor pathways and non-classical estrogen response element(s) which are activated by SERMs. These novel response elements may represent natural pathways which respond to estrogen metabolites in vivo.
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PMID:Selective estrogen receptor modulators: an alternative to hormone replacement therapy. 942 Dec 6

The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position -93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.
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PMID:The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. 1044 99

Beta-adrenoceptors are important regulators of cardiac function and their characteristics are known to change in human and canine diseased myocardium. This study aimed to determine the density and subtypes of beta-adrenoceptors in the normal and failing equine ventricular myocardium. Membrane preparations of the left papillary muscles were incubated with increasing concentrations of the nonselective beta-adrenoceptor antagonist [3H]-CGP12177. Saturable and reversible binding of [3H]-CGP12177 to myocardial membranes was demonstrated with Kd values (+/- s.d.) of 0.49 +/- 0.40 and 0.43 +/- 0.22 nmol/l and Bmax values of 93.4 +/- 20.5 and 110.0 +/- 21.2 and fmol/mg protein for normal (n = 19) and heart failure (n = 10) tissues, respectively. Heart failure had no significant effect on the density of ventricular beta-adrenoceptors. The cardiac beta-adrenoceptors were further characterised by studying displacement of [3H]-CGP12177 (0.6 nmol/l) with the beta1-selective antagonists CGP20712A and the beta2-selective antagonist ICI118.551. In normal ventricular muscle, CGP20712A was 26 times more potent than ICI118.551 (Ki values 30.4 +/- 24.8 and 814.1 +/- 485.2 nmol/l, respectively). In heart failure cases, CGP 20712A curves were monophasic with a Ki value of 45.6 +/- 39.7 nmol/l. ICI 118.551 curves were biphasic in 5 horses where 11-31% of the cardiac beta-adrenoceptors had a high affinity for ICI 118.551. These data suggest that the normal equine ventricular myocardium possesses predominately beta1-adrenoceptors, with no evidence for co-existence of a significant population of beta2-adrenoceptors. The density of beta-adrenoceptors did not appear to change in heart failure, but the appearance of receptors with a high affinity for ICI118.551 may suggest that, in some cases, heart failure increases the expression of beta2-adrenoceptors in equine ventricular myocardium. This study provides an insight into the role of the adrenergic system in heart disease in the horse. Further studies in this area are warranted.
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PMID:Density and binding characteristics of beta-adrenoceptors in the normal and failing equine myocardium. 1211 16

Alpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into alpha(1)-, alpha(2)- and beta(1)-, beta(2)-, beta(3)-, beta(4)-adrenoceptors. In cardiac disease, there is often a selective downregulation of beta(1)-adrenoceptors associated with a relative increase in beta(2)- and alpha(1)-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac alpha- and beta-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective beta-adrenoceptor antagonist [(11)C]CGP-12177 was used to quantify beta-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [(11)C]CGP-12388, [(18)F]CGP-12388, [(11)C]carazolol and [(18)F]fluorocarazolol) are currently evaluated; beta(1)-selective radioligands (e. g. [(11)C]CGP-26505, [(11)C]bisoprolol, [(11)C]HX-CH 44) and beta(2)-selective radioligands (e. g. [(11)C]formoterol, [(11)C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET. Potential radioligands for imaging cardiac alpha(1)-adrenoceptors are based on prazosin. Whereas [(11)C]prazosin shows low specific binding to myocardium, its derivative [(11)C]GB67 looks more promising. The putative alpha(2)-adrenoceptor radioligand [(11)C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man. A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.
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PMID:Radioligands for imaging myocardial alpha- and beta-adrenoceptors. 1260 47

Background / Objectives. Atrial fibrillation (AF) is a very frequent and complex disease often associated with other medical conditions. The Euro Heart Survey (EHS) on AF showed that adherence to guidelines may reduce morbidity and mortality in AF patients. Therefore a nurse-driven, guideline-based, ICT-supported integrated chronic care program (ICCP) was developed and implemented in daily practice. The objective of this study is to evaluate the clinical feasibility of the ICCP, with guideline adherence as the endpoint.Methods. 111 ambulant patients referred for treatment of their AF were enrolled in the ICCP. In this group, patients underwent standardised clinical testing and were subsequently managed by a nurse, supported by a dedicated ICT program and supervised by cardiologists. For comparison, we used a recent historical control group of 102 patients who participated in the Maastricht part of the Euro Heart Survey (EHS) on AF. Results. Guideline adherence was excellent within the ICCP and compared favourably with the EHS-AF data concerning both clinical testing (trigger factors recorded in 100 vs. 44%; echocardiogram performed in 99 vs. 88%; thyroid-stimulating hormone level recorded in 96% vs. 63%) as well as treatment (antithrombotic therapy in 90 vs. 78%; rhythm control avoided in completely asymptomatic patients in 100 vs. 54%; class I drugs avoided in patients with structural heart disease in 90 vs. 95%; rhythm control avoided in permanent AF patients in 100 vs. 92%). Conclusion. The high level of guideline adherence suggests that a nurse-driven, guideline-based, ICT-supported ICCP for AF patients is feasible. (Neth Heart J 2010;18:471-7.).
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PMID:Improving guideline adherence in the treatment of atrial fibrillation by implementing an integrated chronic care program. 2097 91