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)

There are several indications that the oxygen supply to the myocardium is inadequate in chronic heart failure. This is due to an increased intramyocardial vascular resistance, elevated filling pressures, and a shortened diastolic perfusion time. In parallel, the myocardial oxygen demand is heightened due to elevated wall stress, heart rate and contractility. This imbalance between myocardial oxygen supply and demand might be the cause of the adaptive metabolic changes seen in severe chronic heart failure. We showed increased LDH 5, decreased LDH 1 and increased ADP/ATP-carrier concentration in the myocardium from patients with chronic heart failure. After ACE-inhibitor treatment in 33 patients with chronic heart failure, LDH 1 increased from 38.7 +/- 6.7% to 42.3 +/- 5.5% (P less than 0.005) paralleled by a decrease in LDH 5 from 20.8 +/- 7.0% to 15.8 +/- 4.7% (P less than 0.001). The ADP/ATP-carrier concentration also decreased significantly within the normal range. This shift in the LDH isoenzyme pattern and decrease in the ADP/ATP-concentration can be interpreted as an indication for an improvement of myocardial energy balance in chronic heart failure under ACE-inhibitor therapy. This might help interrupt the self-perpetuation of chronic heart failure which is partially caused by a progressive subendocardial perfusion deficit.
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PMID:The effect of ACE inhibition on myocardial energy metabolism. 236 54

1. Dopexamine is a novel analogue of dopamine which is free of alpha-adrenoceptor activity and is of therapeutic value in chronic heart failure. The effects of dopexamine on the in vitro function of platelets from 10 healthy subjects at rest, after exercise and after in vitro addition of adrenaline and noradrenaline were investigated. 2. Dopexamine in a wide range of concentrations (10(-9)M-10(-3)M) did not appear to function as an agonist on platelets either in whole blood or in PRP preparations. 3. Dopexamine caused a dose-dependent inhibition of agonist-induced platelet aggregation in both whole blood and PRP. The inhibitory effect of dopexamine was significantly greater in PRP than in whole blood, and significantly greater to adrenaline than to collagen or ADP as agonists in whole blood. 4. After exercise or after in vitro addition of adrenaline and noradrenaline at concentrations commonly seen in myocardial infarction, dopexamine produced similar levels of inhibition seen with platelets from resting subjects. 5. Dopexamine did not affect plasma catecholamine levels but caused an increase in intraplatelet noradrenaline levels. 6. This study suggests that dopexamine is unlikely adversely to affect the hyperaggregable state found in patients with cardiogenic shock after myocardial infarction.
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PMID:The effects of dopexamine, a new dopamine analogue, on platelet function in stress. 239 Apr 35

A degree of platelet aggregation in patients with dilatation cardiomyopathy (DCMP) with different stages of heart failure (HF) was evaluated with the help of a highly sensitive aggregometer developed in the All-Union Cardiological Research Center AMS USSR. The main advantage of this modification was a possibility to study platelet aggregation in response to small doses of an inductor (e.g. less than 0.2 microM of ADP) that could not be done using routine methods. A significant rise of a degree of platelet aggregation was revealed in patients with 0-I,IIA stages of DCMP and IIB-III stages of HF in response to 0.1 microM of ADP. Platelet aggregation was enhanced with an increase in a HF stage. The addition of a higher concentration of ADP (0.2-0.5 microM) and the platelet aggregation factor (5 and 25 nM) revealed no rise of platelet aggregation in patients with 0-I stages of DCMP and IIA stage of HF. Only in patients with stages IIB-III of HF was a platelet aggregation index significantly raised in response to 0.2 and 0.5 microM of ADP but to a much lesser degree than in the addition of 0.1 microM of ADP.
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PMID:[New approaches to the study of thrombocyte aggregation in patients with dilated cardiomyopathy]. 272 28

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

The oxidative phosphorylation as well as calcium transporting properties of heart mitochondria and calcium transport activities of the fragments of the sarcoplasmic reticulum (microsomes) were studied during the life span of cardiomyopathic hamsters (UM-X7.1). Control healthy hamsters of the same age group were used for comparison. No changes in the oxidative phosphorylation ability of cardiomyopathic mitochondria were seen at early and moderate stages of heart failure; however, at severe stages, mitochondrial respiratory functions, but not the ADP:0 ratio, were impaired. Both creatine phosphate and ATP contents were decreased without any significant changes in the ATPase activities of myofibrils from the failing hearts. Heart mitochondria from cardiomyopathic animals at severe stages of failure exhibited less calcium binding and uptake activities in comparison with the control values whereas no changes in the mitochondrial calcium binding and uptake were seen in cardiomyopathic hamsters which showed no clinical signs of heart failure. Although mitochondrial calcium binding in cardiomyopathic hearts at early and moderate stages of failure was decreased, mitochondrial calcium uptake was not significantly different from the control. Microsomal calcium binding activity, unlike calcium uptake activity, was decreased in the hearts of cardiomyopathic hamsters without any signs of heart failure. Both calcium binding and calcium uptake activities of microsomes from animals with early, moderate and severe heart failure were less in comparison with the control values but were not associated with any changes in the Ca2+-stimulated ATPase activity. These results suggest that changes in the process of mitochondrial energy production and mitochondrial Ca2+-transport may be secondary to other factors whereas alterations in the sarcoplasmic reticular Ca2+-transport may lead to the development of heart failure in the cardiomyopathic hamsters.
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PMID:Impairment of mitochondrial and sarcoplasmic reticular functions during the development of heart failure in cardiomyopathic (UM-X7.1) hamsters. 294 28

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.
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PMID:Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster. 394 35

A clinically relevant model of heart failure has been developed in chronically instrumented mini-pigs by injecting Sephadex beads into the left main or circumflex coronary arteries under fluoroscopic control. In six control animals, left atrial pressure (LAP) increased from 10 +/- 2 to 19 +/- 2 mmHg (p less than 0.01) and remained elevated for 3 days. Heart rate increased by 26 beats X min-1 (p less than 0.05) and diastolic pressure fell after 24 h but recovered over the next 48 h. In six animals treated with ticlopidine (50 mg X kg-1 p.o.) for four days prior to embolisation, the acute haemodynamic changes were less in the first day but similar to control after 3 days. Infarct size was approximately 20% of the left ventricle in control animals and 9.5% in the treated group (p less than 0.01). ADP-induced platelet activity was reduced in the treated animals suggesting that coronary occlusion followed both physical occlusion by the beads and later development of platelet thrombi.
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PMID:A clinically relevant model of heart failure: effects of ticlopidine. 400 94

The development of myocardial infarction was shown to be accompanied by a rise in blood cAMP, cGMP and AMP levels, cyclic nucleotides peaking within the first hours of the disease. The increase in plasma cAMP, associated with developing heart failure, was more persistent. The administration of GIP mixture during the acute phase of myocardial infarction was conducive to lowering the levels of cyclic nucleotides and AMP, and raising blood ATP and ADP values. Clinically, the effect of GIP was manifested in reduced ventricular arrhythmias and diminished signs of heart failure.
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PMID:[Effect of a glucose-insulin-potassium mixture on the cyclic and adenine nucleotide levels in the acute period of myocardial infarct]. 633 82

Three metabolic adaptive or compensatory mechanisms of heart failure were discussed: Adaptation of energy production and of energy availability in the myocardial cell. With increased myocardial oxygen demands this is achieved by a progressive displacement of the mass action ratio of the creatine phosphokinase reaction, so that pronounced changes in the creatine phosphate-ratio, related to myocardial oxygen consumption, are accompanied by only small changes in adenosine-5'-triphosphate adenosine-5'-diphosphate and hence in free energy of the adenine-nucleotide system. Adjustment of the oxygen availability by adaptation of the hemoglobin dissociation curve due to an increase in the erythrocyte content of 2, 3-diphosphoglycerate. This is accompanied by a swelling of erythrocytes as a consequence of an increase in the Gibbs-Donnan potential. In patients with congestive heart failure 2,3-diphosphoglycerate-synthesis is augmented due to respiratory alkalosis and increased concentrations of deoxygenated hemoglobin. Increase in the sympathetic drive of the heart due to increased net discharge of the neurotransmitter caused by reduced neuronal reuptake of norepinephrine. The diminished myocardial norepinephrine content in heart failure is due to the diminished neuronal uptake and to insufficient de novo catecholamine synthesis in the heart. Rather than tyrosine-hydroxylase the transformation of dopamine to norepinephrine seems to be the rate limiting step for catecholamine synthesis in heart failure.
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PMID:Metabolic aspects of compensatory mechanisms in cardiac failure. 651 Jun 22

The following studies were carried out to examine energy metabolites and cardiac performance of the failing heart (hereditary cardiomyopathy) of the Syrian hamster (strain UM-X7.1) perfused either by normal or stress conditions, and to determine whether cyclical changes in energy-related metabolites occurred in the glucose-perfused hearts of both normal and heart failure animals. Hamster hearts from 250-day-old animals with moderate heart failure were removed and perfused either as nonworking hearts (Langendorff method, an afterload pressure of 90 mm Hg and 2.5 mM calcium in the perfusate) or as working hearts with stress conditions [an afterload of 110 mm Hg, high calcium concentrations in the perfusate (3.5 mM), and 10(-8) M isoproterenol]. Mechanical parameters (developed pressure and max dP/dt) and measurements of oxygen consumption indicated that both contractility and oxygen consumption had fallen 50% in myopathic hearts, compared with those of normal hamsters perfused with either of the two conditions. By means of a specially designed stimulator-triggered freeze clamp, hearts were terminated at systole and diastole, and tissue content of ATP, ADP, AMP, adenosine, phosphocreatine, creatine, pyruvate, lactate, and inorganic phosphate were analyzed. A 50% reduction in cardiac performance of the cardiomyopathic hamster hearts was associated with a corresponding reduction in systolic ATP, adenosine, and phosphocreatine values, while inorganic phosphate and lactate increased. With glucose as the sole substrate, the high energy phosphates, ATP and phosphocreatine, reached maximum values during diastole and minimum values during systole.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy levels at systole vs. diastole in normal hamster hearts vs. myopathic hamster hearts. 664 Aug 62


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