UMLS:C0018801 - FACTA Search

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

The purpose of the study was to examine the cardiovascular and cardiopulmonary exercise capacity in patients with symptomatic congestive heart failure more exactly than with conventional investigations, using the simultaneous non-invasive determination of the gas exchange parameters (ergospirometry, CPX) and of the hemodynamic (transthoracic bioimpedance). The reproducibility of the data were measured with each method with repeated tests under the same conditions in healthy subjects and patients with myocardial failure. Therefore we tested 15 patients with documented congestive heart failure repeatedly on a bicycle (semi-supine, +15 watts/min, symptom-limited). The ergospirometric (VO2, VCO2, RER = VCO2/VO2, max. VO2, VO2AT, VE, RR) and the bioimpedance-parameters (CI, SVI, HR) were measured simultaneously during rest and exercise. According to Wasserman et al. we used the VO2AT and the max. VO2 to assign the patients to the different Weber classes: Weber A: greater than 20 ml/min/kg max. VO2, greater than 14 ml/min/kg VO2AT; Weber B: 16 to 20 ml/min/kg max. VO2, 11 to 14 8 to 11 ml/min/kg VO2AT; Weber D: 6 to 10 ml/min/kg max. ml/min/kg VO2AT; Weber C: 10 to 16 ml/min/kg max. VO2, 8 to 11 ml/min/kg VO2AT; Weber D: 6 to 10 ml/min/kg max. VO2, 4 to 8 ml/min/kg VO2AT: Weber E: less than 6 ml/min/kg max. VO2, less than 4 ml/min/kg VO2AT. The V-slope-method according to Beaver et al. allowed for the determination of the anaerobic threshold in 13/15 patients. 2/15 patients didn't reach the anaerobic threshold. Oscillations of the gas exchange parameters due to Cheyne-Stokes-breathing were found in 9/15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiopulmonary exercise testing (CPX) and transthoracic bioimpedance measurements: new tools for an "old disease" (congestive heart failure). 182 Mar 2

Since December 1985, we have performed 38 transplantations: cardiac (CT) n: 31, cardiopulmonary (CPT) n: 1, or bipulmonary (BPT) n: 6. There were 31 male and 7 female patients, aged 7 to 62, mean 46. In the cardiac group, the cardiomyopathy was primitive in 13, ischemic in 16, valvular in 2. Five patients had undergone one or more previous operations. Three patients had a biventricular assist device (1,6 and 7 days before transplant) for acute cardiac failure. The indication of CPT or BPT was pulmonary artery hypertension (1), silicosis (1), cystic fibrosis (4). There were 4 post-operative deaths in the CT group (12.9%); failure of graft, low cardiac output, pulmonary artery hypertension by multiple pulmonary thrombosis, and 2 deaths in the CPT and BPT groups (28%). The mean post-operative hospital stay was one month. All patients with CT were treated by an initial maintenance bitherapy protocol (cyclosporine, steroids) and observed by myocardial biopsies and echocardiograms. In 40 per cent of the patients, Azathioprine was subsequently added. The patients had 2.1 rejection episode/patient/year, either spontaneously reversed of treated medically. There were two late deaths (2 and 7 months) by refractory rejection. 78 per cent of the patients were alive one year after transplant. All survivors have recovered a normal life, some of them with full-time work.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Heart and heart-lung transplantation. 3 years' experience in Timone CHU (Marseilles 1985-1988)]. 210 56

1. The decreased response to beta-adrenoceptor stimulation seen in heart failure may be related to a defect in cyclic AMP production. The inotropic effects of the selective phosphodiesterase (PDE) III inhibitors, SK&F 94120 and SK&F94836, and the non-selective PDE inhibitor, 3-isobutyl-l-methylxanthine (IBMX), alone and when combined synergistically with isoprenaline, were studied in control and beta-adrenoceptor-desensitized ventricular myocytes. 2. Myocytes isolated from noradrenaline-treated guinea-pigs had a reduced maximum response to isoprenaline compared with control animals (60.0 +/- 2.5%, n = 42 vs 79.5 +/- 1.7% maximum calcium: n = 46, P < 0.001). Together with an approximately 20 fold increase in the isoprenaline EC50, this is indicative of beta-adrenoceptor desensitization as a result with chronic infusion with noradrenaline. 3. The maximum inotropic response of IBMX was depressed following noradrenaline treatment, from 74.9 +/- 4.6% (n = 7) in control, to 61.7 +/- 2.70% (n = 6), as a percentage of maximum calcium in noradrenaline-treated guinea-pig ventricular myocytes (P < 0.02). The pD2 value for IBMX was also reduced (P < 0.02). No significant differences in the inotropic effects of SK&F94120 and SK&F94836 were seen between control and beta-adrenoceptor desensitized myocytes. 4. Threshold inotropic concentrations of SK&F94120 and SK&F94836 caused a five fold decrease in the EC50 of control myocytes for isoprenaline, and an 11 fold decrease in the noradrenaline-treated guinea-pig ventricular myocytes. 5. The maximum response to isoprenaline in myocytes isolated from normal guinea-pigs was unaffected by PDE inhibition; either at threshold or maximum inotropic concentrations, or by CPT cyclic AMP, an analogue of cyclic AMP.6. A significant potentiation of the maximum isoprenaline response by threshold inotropic concentrations was observed with SK&F 94120 (P<0.05), but not with IBMX or SK&F 94836, in myocytes isolated from noradrenaline-treated guinea-pig hearts. This potentiation, however, did not completely restore the response to levels seen in control myocytes.7. The extent of potentiation of the maximum isoprenaline response by maximum inotropic concentrations of either IBMX or CPT cyclic AMP, was no greater than that by threshold concentrations of IBMX, in myocytes isolated from noradrenaline-treated guinea-pig hearts.8. In cardiac myocytes isolated from the explanted hearts of 16 patients with heart failure, threshold concentrations of IBMX and SK&F 94120 decreased the isoprenaline EC50 by a factor of four and six,respectively, but potentiation of the maximum isoprenaline response occurred only with SK&F 94120.The attenuated isoprenaline response was increased from 60.3 +/- 4.5% to 74.3 +/- 4.2% as a % maximum calcium (P<0.05, n = 6), but remained substantially lower than the 116 +/- 7% (P<0.001, n = 6) seen in myocytes isolated from non-failing hearts.9. We conclude that the reduced maximum contraction amplitude with isoprenaline in cardiac myocytes from either patients in end-stage failure, or noradrenaline-treated guinea-pigs, is partly but not solely due to insufficient cyclic AMP levels, since inhibition of cyclic AMP degradation does not result incomplete reversal of the beta-adrenoceptor desensitization.
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PMID:Incomplete reversal of beta-adrenoceptor desensitization in human and guinea-pig cardiomyocytes by cyclic nucleotide phosphodiesterase inhibitors. 769 63

The reproducibility of blood gas exchange measurements on exercise in chronic cardiac failure has already been established in patients familiar with this technique. The aim of this prospective study was to evaluate the reproducibility of cardiopulmonary parameters on exercise in a population of patients who had never undergone this type of investigation. Twenty patients with chronic cardiac failure in classes I to III of the NYHA classification, with a mean age of 55 +/- 11.5 years and a mean LV ejection fraction of 31.2 +/- 9%, underwent two cardiopulmonary exercise tests (CPX Medgraphic) performed on a bicycle ergometer. Patients underwent maximal exercise stress testing attaining 89% of the theoretical maximal heart rate and 1.14 of the respiratory quotient during the first test. There was no significant change in peak VO2 (22.5 ml/min/kg vs 22.6 ml/min/kg) or in ventilatory anaerobic threshold (12.8 ml/min/kg vs 12.7 ml/min/kg) between the two tests. The ventilatory anaerobic threshold could not be measured in one patient and seemed less reproducible than peak VO2 with a standard deviation of relative differences (T2-T1/T1) of 10.4 versus 7.8%. There was a significant increase in the duration of exercise (7.4 +/- 9.2%; p < 0.002) and a ventilatory flow (4.5 +/-, p = 0.03). This study shows that peak VO2 is a reproducible measurement in mild to moderate chronic cardiac failure, even in the absence of a preliminary test to familiarize the patient with the equipment. The reproducibility of the ventricular anaerobic threshold is less satisfactory than that of peak VO2. The increase in the duration of exercise is more dependent on motivation and should not be taken into account alone in the functional evaluation of chronic cardiac failure.
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PMID:[Reproducibility of measurements of blood gas exchange during exercise in mild cardiac failure: need for a preliminary test?]. 923 65

Heart transplantation has recently become an accepted method of treating heart failure patients, also in Poland. Criteria of patient selection to heart transplantation and follow-up was based (and in some centers still is) on the assessment of the patients' clinical status according to NYHA classification and on the data on the extend of myocardial damage obtained from echocardiography or ventriculography at rest. However, examinations performed in the resting state do not provide complete information on the patient's clinical status, especially during increased oxygen demand. Recently cardiopulmonary exercise testing (CPX-to measure maximal oxygen consumption) has been increasing used to establish the prognosis in patients with severe heart failure and to define indications to heart transplantation. CPX combines exercise testing with monitoring the air flow and gas exchange. The measurement of oxygen uptake and anaerobic threshold during exercise is an objective, reproducible, safe and non-invasive method to assess cardiac reserve. There is evidence implying that in heart failure patients VO2max is a good short-term indicator of mortality and that its deterioration frequently precedes clinical decompensation. Thus, the parameter may be useful not only in defining the indications, but also in the monitoring the patient's clinical state and timing of heart transplantation.
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PMID:[Clinical usefulness of cardiopulmonary exercise testing in patients with cardiac failure waiting heart transplantation]. 950 96

This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular production of cGMP, forearm blood flow, and neurohormonal factors during continuous transdermal application of nitroglycerin in patients with chronic heart failure. Platelet cGMP level and forearm blood flow were measured before and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients with chronic heart failure during the following 4 phases: (1) baseline phase; (2) NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before sublingual NTG and forearm blood flow were significantly higher during the 3 phases with NTG tape than during the control phase. The percent increases in platelet cGMP level and forearm blood flow after sublingual NTG were significantly lower during the NTG phase than during the baseline phase. In contrast, concomitant application of ACE inhibitors maintained the percent increase in platelet cGMP level and forearm blood flow. These results indicate that concomitant therapy with ACE inhibitors may be helpful in preventing the attenuation of intracellular cGMP production in patients with chronic heart failure during continuous transdermal application of NTG.
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PMID:Preventive effects of angiotensin-converting enzyme inhibitors on nitrate tolerance during continuous transdermal application of nitroglycerin in patients with chronic heart failure. 962 3

Inhibitors of carnitine palmitoyl-transferase I (CPT I), the key enzyme for the transport of long-chain acyl-coenzyme A (acyl-CoA) compounds into mitochondria, have been developed as agents for treating diabetes mellitus Type 2. Findings that the CPT I inhibitor, etomoxir, has effects on overloaded heart muscle, which are associated with an improved function, were unexpected and can be attributed to selective changes in the dysregulated gene expression of hypertrophied cardiomyocytes. Also, the first clinical trial with etomoxir in patients with heart failure showed that etomoxir improved the clinical status and several parameters of heart function. In view of the action of etomoxir on gene expression, putative molecular mechanisms involved in an increased expression of SERCA2, the Ca(2+) pump of sarcoplasmic reticulum (SR) and alpha-myosin heavy chain (MHC) of failing overloaded heart muscle are described. The first 225 bp of human, rabbit, rat and mouse SERCA2 promoter sequence have high identity. Various cis-regularory elements are also given for the promoter of the rat cardiac alpha-MHC gene. It is hypothesised that etomoxir increases glucose-phosphate intermediates resulting in activation of signalling pathway(s) mediated by phosphatases. Regarding the possible direct action of etomoxir on peroxisome proliferator activated receptor alpha (PPAR-alpha) activation, it could upregulate the expression of various enzymes that participate in beta-oxidation, thereby modulating some effects of CPT 1 inhibition. Any development of alternative drugs requires a better understanding of the signal pathways involved in the altered gene expression. In particular, signals need to be identified which are altered in overloaded hearts and can selectively be re-activated by etomoxir.
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PMID:Therapeutic potential of CPT I inhibitors: cardiac gene transcription as a target. 1186 64

beta(1)-adrenergic receptor (beta(1)AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of metabolism, muscle contraction, and cell apoptosis. Here we show that sustained beta(1)AR stimulation promotes cardiac myocyte apoptosis by activation of Ca(2+)/calmodulin kinase II (CaMKII), independently of PKA signaling. beta(1)AR-induced apoptosis is resistant to inhibition of PKA by a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue, Rp-8-CPT-cAMPS. In contrast, the beta(1)AR proapoptotic effect is associated with non-PKA-dependent increases in intracellular Ca(2+) and CaMKII activity. Blocking the L-type Ca(2+) channel, buffering intracellular Ca(2+), or inhibiting CaMKII activity fully protects cardiac myocytes against beta(1)AR-induced apoptosis, and overexpressing a cardiac CaMKII isoform, CaMKII-deltaC, markedly exaggerates the beta(1)AR apoptotic effect. These findings indicate that CaMKII constitutes a novel PKA-independent linkage of beta(1)AR stimulation to cardiomyocyte apoptosis that has been implicated in the overall process of chronic heart failure.
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PMID:Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. 1261 12

Recent human and animal studies have demonstrated that in severe end-stage heart failure (HF), the cardiac muscle switches to a more fetal metabolic phenotype, characterized by downregulation of free fatty acid (FFA) oxidation and an enhancement of glucose oxidation. The goal of this study was to examine myocardial substrate metabolism in a model of moderate coronary microembolization-induced HF. We hypothesized that during well-compensated HF, FFA oxidation would predominate as opposed to a more fetal metabolic phenotype of greater glucose oxidation. Cardiac substrate uptake and oxidation were measured in normal dogs (n = 8) and in dogs with microembolization-induced HF (n = 18, ejection fraction = 28%) by infusing three isotopic tracers ([9,10-(3)H]oleate, [U-(14)C]glucose, and [1-(13)C]lactate) in anesthetized open-chest animals. There were no differences in myocardial substrate metabolism between the two groups. The total activity of pyruvate dehydrogenase, the key enzyme regulating myocardial pyruvate oxidation (and hence glucose and lactate oxidation) was not affected by HF. We did not observe any difference in the activity of carnitine palmitoyl transferase I (CPT-I) and its sensitivity to inhibition by malonyl-CoA between groups; however, malonyl-CoA content was decreased by 22% with HF, suggesting less in vivo inhibition of CPT-I activity. The differences in malonyl-CoA content cannot be explained by changes in the Michaelis-Menten constant and maximal velocity for malonyl-CoA decarboxylase because neither were affected by HF. These results support the concept that there is no decrease in fatty acid oxidation during compensated HF and that the downregulation of fatty acid oxidation enzymes and the switch to carbohydrate oxidation observed in end-stage HF is only a late-stage phenomenon.
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PMID:Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation. 1519 96

The apoptosis of cardiomyocytes plays a pivotal role in the pathogenesis of cardiac failure transformed from cardiac hypertrophy, so that suppression of cardiomyocytes apoptosis is an effective pharmacotherapeutic target to prevent cardiac failure. This study focused on the relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. Cardiomyocyte hypertrophy was induced by angiotensin II (0.1 mumol/L ) and norepinephrine (1 mumol/L), and the cells were cultured under the condition of hypoxia ( 95% N2 and 5% CO2, the O2 partial pressure was regulated at least lower than 5 mmHg ) for 8 h, then were recovered to normal culture environment. Apoptosis was detected with TUNEL. The activity of pyruvate dehydrogenase (PDH) and carnitine palmitoyltransferase 1 (CPT-1), the rate of glycose oxidation and glycolysis, and fatty acid metabolism were detected by liquid scintillation counting. The results are as follows: (1) The activity of active PDH (PDHa) was slightly higher in hypertrophic cardiomyocytes than that in normal cardiomyocytes, but the activity of CPT-1 was significantly lower in hypertrophic cardiomyoctes than that in normal cardiomyocytes.Compared with the hypertrophic cardiomyocytes cultured with normal oxygen concentration, the activities of PDHa and CPT-1 were decreased significantly after hypoxia for 8 h, and the activity of PDHa were decreased further after reoxygenation for 4 h, but the activity of CPT-1 recovered quickly after reoxygenation. (2) The rate of glucose oxidation in hypertrophic cardiomyocytes increased slightly when cultured under normal O2 partial pressure than that in normal cardiac cells. The rate of glucose oxidation reduced (16 +/- 0.9)% and (48 +/- 1.1)% in normal and hypertrophic cardiomyocytes, respectively, after hypoxia. It reduced further in hypertrophic cardiac cells at 4 h of reoxygenation, then recovered gradually. In normal cardiocytes, it recovered quickly after reoxygenation. (3) The rate of glycolysis of hypertrophic cardiocytes increased slightly than that of the normal cardiocytes when cultured in the general O(2) environment. Compared with the normal cardiomyocytes, the rate of glycolysis of hypertrophic cardiac cells was the same during hypoxia-reoxygenation culture, i.e., the rate of glycolysis decreased slightly after hypoxia for 8 h, but increased rapidly and significantly after reoxygenation. (4) The rate of fatty acid oxidation was slightly lower in hypertrophic cardiocytes than that in normal cardiomyocytes. After hypoxia for 8 h, the rate of fatty acid oxidation decreased significantly in normal and hypertrophic cardiomyocytes, there was no difference between normal and hypertrophic cardiomyocytes. But the alterations of fatty acid oxidation after reoxygenation were different between normal and hypertrophic cardiac cells, namely, the fatty acid oxidation of normal cardiomyocytes were activated slowly and slightly, while the rate of fatty acid oxidation of hypertrophic cardiomyocytes increased markedly at the early stage of reoxygenation, and increased further at 8 h of reoxygenation. (5) The rate of apoptosis in hypertrophic cardiocytes increased obviously after hypoxia for 8 h, and increased further and markedly at the early stage of reoxygenation, then gradually decreased to normal level. (6) Dicholoroacetate could inhibit apoptosis of hypertrophic cardiocytes through increasing glucose oxidation and inhibiting the activation of glycolysis and fatty acid oxidation of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. These data demonstrate that apoptosis in hypertrophic cardiomyocytes after hypoxia-reoxygenation is mainly due to the inhibition of glucose oxidation and the activation of glucolysis and fatty acid oxidation. Furthermore, increasing glucose oxidation may be a new pharmacotherapeutic target to inhibit apoptosis of hypertrophic cardiac cells.
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PMID:[Relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation]. 1622 Feb 3

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