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 phenomenon of postexcitatory depression (PED) of baroreceptors is related to augmentation of Na(+)- K(+) -adenosinetriphosphatase (ATPase) activity. To provide additional evidence to support the hypothesis that dogs with chronic heart failure have augmented Na(+) -K(+) -ATPase activity in baroreceptor endings, the present study was undertaken to compare the duration of the PED of carotid sinus baroreceptors from normal and heart failure dogs. The effect of perfusion of the carotid sinus with a cardiac glycoside was also investigated. Eight normal and six dogs with experimental heart failure induced by ventricular pacing (250 beats/min for approximately 5 wk) were used in this study. Dogs were anesthetized, and the carotid sinus was isolated and perfused. Single baroreceptor units from the carotid sinus nerve were recorded, and the duration of the PED was measured. The relationship between the magnitude of the pressure steps and the duration of PED was determined. Duration of PED was significantly prolonged in the heart failure group at each pressure step (range from 2.7 to 9.0 s compared with 0.5 to 2.9 s in normal dogs). For the relationship between the duration of the pressure step and duration of PED, the heart failure dogs exhibited a markedly longer duration of PED than the normal dogs (range from 2.3 to 12.4 s compared with 0.5 to 5.3 s in normal dogs). Perfusion of the carotid sinus with very low doses of ouabain decreased the duration of PED in the heart failure dogs; however, there was no such effect in the normal dogs. These data are consistent with the view that baroreceptor membranes have increased Na(+) -K(+) -ATPase activity in heart failure(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postexcitatory depression of baroreceptors in dogs with experimental heart failure. 184 69

Advances in regulation by secondary messengers of Ca2+ level in cardiomyocyte and vascular smooth muscle cell cytosols with special reference to the major differences in regulatory effects in cells of the both types are reviewed. The effects of cAMP, cGMP, Ca2+, calmodulin, diacylglycerol and polyphosphoinositides on the Ca(2+)-channel, Ca(2+)-ATPase, plasmalemma, sarcoplasmic reticulum and outer membrane Na+/Ca2+ uniporter function are considered. Compartmentation of secondary messengers and protein kinase in cardiac and vascular smooth muscle cells should be taken into consideration during extrapolation of in vitro data to an in situ situation. The feasible role of impaired phosphorylation of membrane-bound proteins of cardiac and vascular smooth muscle cells in cardiac insufficiency and atherosclerosis is discussed.
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PMID:[Second messengers in heart cells and smooth muscle vessels]. 191 66

The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p less than 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p less than 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms.
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PMID:Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle. 193 53

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2(+)-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2(+)-ATPase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P less than 0.01 and -47%, P less than 0.05, respectively). The LV ratio of Ca2(+)-ATPase mRNA to 18S RNA positively correlated with cardiac index (P less than 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P less than 0.02, P less than 0.02, and P less than 0.01, respectively). We suggest that a decrease of the SR Ca2(+)-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.
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PMID:Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. 213 64

Studies in animal models have suggested that alterations affecting phospholamban-mediated stimulation of Ca2+ uptake by sarcoplasmic reticulum are involved in the pathophysiology of heart disease. A monoclonal antibody that binds to phospholamban and stimulates Ca2+ uptake was used to characterize phospholamban-mediated effects in human cardiac sarcoplasmic reticulum and to compare these effects in tissue from normal and failing hearts. Stimulation of Ca2+ uptake by anti-phospholamban monoclonal antibody simulated the effect of phosphorylation of phospholamban by cAMP-dependent protein kinase. Binding of anti-phospholamban antibody reduced the K0.5 of the Ca2(+)-transporting ATPase from 0.53 microM [( Ca2+]) to 0.29 microM [( Ca2+]), without affecting Vmax or nHill. At 0.2 microM Ca2+, stimulation was 1.93-fold in sarcoplasmic reticulum prepared from normal human left ventricular myocardium and 1.94-fold in sarcoplasmic reticulum prepared from the left ventricular myocardium of patients with heart failure resulting from idiopathic dilated cardiomyopathy. Stimulation of Ca2+ uptake in canine cardiac sarcoplasmic reticulum under identical conditions was 1.89-fold. Phospholamban-mediated stimulation of Ca2+ uptake in human cardiac sarcoplasmic reticulum is thus comparable in magnitude to that observed in other species and results from an increase in the apparent affinity of the Ca2(+)-transporting ATPase for Ca2+. The pathogenesis of heart failure in idiopathic dilated cardiomyopathy does not, however, appear to involve intrinsic alterations of this mechanism.
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PMID:Phospholamban-mediated stimulation of Ca2+ uptake in sarcoplasmic reticulum from normal and failing hearts. 213 70

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca2(+)-dependent Mg-ATPase and myosin Ca2(+)- and K+EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca2(+)-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca2+ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca2(+)-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.
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PMID:Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure. 214 90

During hypoxic heart failure, inorganic phosphate (Pi) accumulates. We report the effects of Pi on force development and on myofibrillar ATPase-activity of human skinned atrial fibers, both at normal and at reduced levels of Mg-ATP. Pi (10 mM) depressed force production at maximal calcium activation (pCa 4.3) by about 40%. At higher pCa values (pCa 5.6), force inhibition was even more pronounced, but at low concentrations of Mg-ATP (10 microM), Pi was less effective. In contrast to contractile force, myofibrillar ATPase was only inhibited by about 10% at pCa 4.3, whereas it could be inhibited by 40-50% at submaximal calcium activation (pCa 5.6). As Pi inhibited contractile force more than ATPase activity, the ratio of ATPase-activity to force (tension cost) was increased by inorganic phosphate. ATPase-activity and tension cost were significantly reduced by lowering Mg-ATP concentration to 10 microM, whereas contractile force was less affected. Pi did not affect ATPase under these conditions at 10 mM Mg-ATP. Pi also shifted the calcium-force relationship towards higher Ca++ concentrations, that is, it decreased calcium sensitivity. In contrast, the calcium sensitivity of myofibrillar ATPase was less affected. These findings suggest that inorganic phosphate may affect the myocardium by altering crossbridge kinetics rather than the calcium affinity of troponin-C. Because of its inhibitory effect on myofibrillar ATPase, inorganic phosphate may be partly cardioprotective in the hypoxic myocardium. However, this "energy sparing' effect is probably offset by the greater "tension cost' that decreases the "efficiency' of tension maintenance in the presence of inorganic phosphate.
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PMID:Inorganic phosphate inhibits contractility and ATPase activity in skinned fibers from human myocardium. 214 47

Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed cardiac tumors asymmetrically in the right atrium. Features associated with cardiac failure, including increased plasma creatine kinase activity (MM and MB) and ventricular dysrhythmias, also were associated with atrial tumor growth. These atrial tumors were able to grow at histocompatible sites (subcutaneously in syngeneic animals) for protracted periods of time yielding a series of transplantable atrial tumor lineages. The transplantable tumors displayed several cardiac-specific characteristics, such as endogenous electrical activity and expression of cardiac-specific proteins. These transplantable atrial tumors constitute a novel experimental resource for developing cell lines which display an adult cardiac phenotype.
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PMID:Cardiac tumors and dysrhythmias in transgenic mice. 215 Oct 59

Alterations of cardiac contractility caused by thiamine deficiency were studied on three groups of 2 month old male Wistar rats: B1, fed a thiamine deficient diet, PF pair fed, which received an amount of thiamine free diet determined on the daily consumption of B1 animals, supplemented with appropriate thiamine supply, C ad libitum fed controls. The animals were studied after 35 days of dietary treatment. Force-velocity curves were determined in right ventricle papillary muscles. Shortening velocity was significantly lower in B1 and PF than in C muscles and in B1 than in PF muscles. The ability to develop tension was not altered. Myosin ATPase activity was assayed in preparations of myofibrils and in preparations of purified myosin. Both Ca-Mg activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were significantly reduced in B1 and PF compared to C myocardium. Furthermore Ca-activated ATPase activity was lower in B1 than in PF myocardium. Myosin isoenzyme distribution was determined by pyrophosphate gel electrophoresis of purified myosin preparations. When compared to C animals both B1 and PF animals showed a myosin electrophoretic pattern shifted towards the slow isoform V3; such a shift was more pronounced in B1 animals. Information concerning excitation-contraction coupling was obtained by determining the steady state and transient force-interval relation and by recording transmembrane action potential. B1 and PF myocardium exhibited, when compared to C, a less sensitivity to a reduction of the interval of stimulation, a faster mechanical restitution, a prolonged action potential duration. Such alterations were generally more pronounced in B1 than in PF myocardium. The results support the view that in the rat cardiac contractility is deeply affected by thiamine deficiency. The alterations of cardiac contractility seem to be caused by adaptive mechanisms rather than by cardiac failure and seem to be attributable for a big part to the reduction of food supply.
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PMID:Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation. 215 36

In this study, the lymphocytes and erythrocytes from peripheral venous blood were used as the study model from which were measured the cellular contents of potassium, sodium, calcium and magnesium in 50 patients with chronic congestive heart failure and 39 control patients. Levels of endogenous digoxin-like substance in the plasma and activities of Na/K ATPase in red cell membrane wer monitored simultaneously. In the patients with heart failure, the intracellular contents of potassium and magnesium were decreased while those of sodium and calcium were increased significantly. The levels of endogenous digoxin-like substance were much higher in the plasma than those either in healthy controls or in patients with heart disease but without congestive failure (273.7 +/- 35.5 vs 23.3 +/- 2.2 and vs 32.9 +/- 3.6 pg/ml, respectively, P less than 0.001 for both). The activities of Na/K-ATPase were much lower in the patients with heart failure than in the controls. Values for intracellular electrolytes were significantly correlated with the rising levels of digoxin-like substance in the plasma. Non-digitalis inotropic therapy was associated with the recovery of these alterations of heart function, with the levels of the digoxin-like substance decreasing and activity of Na/K-ATPase going up. We conclude that endogenous digoxin-like substance might play a role in the imbalance of intra-cellular electrolytes seen in patients with congestive heart failure. Digoxin may exacerbate the loss of intracellular potassium.
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PMID:Intra-cellular electrolyte changes and levels of endogenous digoxin-like substance within the plasma in patients with congestive heart failure. 215 46


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