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

The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure. All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan). We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to beta-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the beta-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.
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PMID:Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium. 838 86

Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.
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PMID:O2 uptake kinetics in response to exercise. A measure of tissue anaerobiosis in heart failure. 844 60

Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation. HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal. Treatment also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload.
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PMID:Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction. 857 37

The aim of our study was to investigate the contribution of physical deconditioning in skeletal muscle metabolic abnormalities in patients with chronic heart failure (CHF). Phosphate metabolism was studied in the leg muscle at rest and during exercise by using phosphate 31 nuclear magnetic resonance spectroscopy in a group of 14 patients with New York Heart Association class II and III CHF and left ventricular ejection fraction <40% and in two groups of age-matched healthy volunteers: one group of 7 sedentary and another of 7 trained subjects. Phosphocreatine depletion rate, intracellular pH, and adenosine diphosphate levels in the muscle during exercise were not statistically different in the CHF patients and in the sedentary healthy subjects, but both groups were statistically different from the trained healthy subjects, who had slower phosphocreatine depletion rates, as well as less intracellular acidosis and lower adenosine diphosphate levels during exercise (p = 0.02; analysis of variance). Our results suggest that metabolic changes occurring in the skeletal muscle of patients with CHF may contribute to the limitation of exercise capacity and are most likely to be a consequence of physical deconditioning because they are very similar to what is observed in sedentary and otherwise healthy subjects as compared with trained subjects.
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PMID:Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure. 860 38

Many patients find polyethylene glycol-based preparations (PEG) difficult to take because of the large volume of fluid they are required to consume. One hundred and sixteen predominantly elderly patients were randomized to receive either sodium phosphate (n = 61) or PEG (n = 55) bowel preparations before colonoscopy. Patients with a history of symptomatic ischaemic heart disease or cerebrovascular disease in the preceding 6 months, severe liver disease or heart failure, or serum creatinine above 200 micrograms/L were excluded from the study. Each patient filled in a questionnaire about the bowel preparation prior to the procedure. The colonoscopists, who were not aware which preparation had been used, were asked to complete a questionnaire about the quality of the bowel preparation after the procedure. The patients found the sodium phosphate preparation slightly more tolerable than PEG. Side effects were slightly more common with sodium phosphate. Neither difference was statistically significant. However, 91% of patients who had previously had PEG found sodium phosphate easier to take. Approximately 25% of patients in each group experienced at least one episode of incontinence. The colonoscopists found no difference in the overall quality of the bowel preparation. The amount of fluid in the colon was greater in patients prepared with PEG. As expected, patients taking sodium phosphate developed hyperphosphataemia (mean phosphate level before colonoscopy 1.56 mmol/L, normal 0.8 -1.3). They also had a lower mean serum potassium level (3.8 mmol/L) than the PEG group (4.2 mmol/L). However, there were no clinically significant consequences. Sodium phosphate was a safe and effective bowel preparation for colonoscopy in this carefully selected group of patients. It was preferred by patients who had previously had PEG. Many elderly patients were found to develop faecal incontinence, irrespective of the type of bowel preparation used.
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PMID:Bowel preparation for colonoscopy: a randomized prospective trail comparing sodium phosphate and polyethylene glycol in a predominantly elderly population. 867 52

In the present work, we studied clinical and haemodynamic correlates of impaired cardiac high-energy phosphate metabolism in patients with heart failure due to dilated cardiomyopathy (DCM). Myocardial 31P-magnetic resonance (MR) spectra were obtained at 1.5 T in 14 volunteers and 23 patients with DCM (mean ejection fraction 34%) in order to quantify the creatine phosphate (CP)/ATP ratio. In addition, patients underwent cardiac catheterization and echocardiography. Compared to volunteers (2.02 +/- 0.11), CP/ATP ratios were significantly reduced in DCM patients (1.54 +/- 0.10; P < 0.05), indicating impaired high-energy phosphate metabolism. CP/ATP ratios correlated with the clinical severity of heart failure estimated from the NYHA class (r = 0.47, P < 0.01); also, CP/ATP correlated with left ventricular ejection fraction (r = 0.54, P < 0.01) and left ventricular end-diastolic wall thickness (r = 0.51, P < 0.01). Thus, 31P-MR spectroscopy can detect abnormal cardiac high-energy phosphate metabolism in patients with heart failure due to DCM. These abnormalities correlate with clinical and haemodynamic parameters. Future studies will have to determine whether 31P-MR spectroscopy can contribute to the routine clinical evaluation of patients with heart failure.
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PMID:Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease. 868 76

In recent years, the striking development of molecular biology and molecular genetic has brought completely new insights into the understanding of heart failure. Two aspects for which significant progress has been made in 1995 are discussed in this review: the genetic mechanisms of inherited cardiomyopathies and the molecular basis of heart failure due to chronic hemodynamic overload. In familial hypertrophic cardiomyopathy, a novel disease gene was found. It encodes myosin binding protein C, whose structure and function are poorly understood. Contractile deficits associated with the myosin mutations were demonstrated, and all this strengthened the hypothesis that hypertrophy is a compensatory mechanism that occurs in presence of a sarcomeric defect. These studies have important prognostic and clinical implications, but new and unexpected concerns have arisen, because a widespread difference in phenotype can be seen in patients harboring similar genotypes. In familial dilated cardiomyopathy, the main findings were the identification of four disease loci, but the genes are still unknown. With respect to the consequences of chronic hemodynamic overload on myocyte function and phenotype, recent data gave rise to lively discussions in the fields of reexpression of fetal troponin T isoforms and of decreased function and expression of the sarco(endo)plasmic reticulum Ca2+ ATPase in the failing human heart; at the moment it is difficult to draw definitive conclusions. Interestingly, three new concepts emerged in the understanding of the pathogenesis of heart failure: the increased contribution of the Na(+)-Ca2+ exchange, the possible recruitment of an inositol phosphate-sensitive calcium pool for myofibrillar activation, and the involvement of apoptotic myocyte and nonmyocyte cell death in myocardial remodeling.
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PMID:Molecular and cellular biology of heart failure. 883 64

A case of anorexia nervosa (AN) is reported where heart failure occurred secondary to severe hypophosphatemia despite oral phosphate supplementation. We recommend starting patients with AN on oral phosphate when refeeding is begun, monitoring serum phosphate every 1 to 2 days for at least the first week of refeeding, and discontinuation of refeeding during phosphate supplementation should severe hypophosphatemia develop.
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PMID:Anorexia nervosa: refeeding and hypophosphatemia. 886 75

The number of atrial angiotensin II binding sites is reduced in end-stage human heart failure. The goals of our study were the development of a quantitative polymerase chain reaction for angiotensin II receptor type 1 mRNA to determine the angiotensin receptor type 1 (AT1) mRNA content in the atria of patients with end-stage heart failure. We established a quantitative PCR based on coamplification of AT1 wild-type and an internal standard in the same PCR, followed by liquid-phase hybridization of PCR products in microtiter plates and quantitation by ELISA. Glyceraldehyde phosphate dehydrogenase mRNA in the same samples was used to relate the AT1 mRNA content to a stably expressed reference gene. Atrial samples from 11 patients with end-stage heart failure obtained at cardiac transplantation were compared with atrial samples from 11 patients with normal cardiac function undergoing routine cardiac surgery. A PCR/ELISA system with a variance of about 6% after reverse transcription and a linear measuring range was established. In the samples from 11 patients with end-stage heart failure a 58% decrease in AT1 mRNA content was found in comparison with 11 controls (heart failure: 185,680 +/- 196,912 AT1 mRNA copies/microgram RNA, controls: 440,555 +/- 268,456, P < 0.02). When AT1 mRNA content was related to glyceraldehyde phosphate dehydrogenase mRNA, a 65% decrease was detected (AT1/glyceraldehyde phosphate dehydrogenase: heart failure: 4.84 +/- 5.18; controls: 13.74 +/- 7.77; P < 0.005). Standardization of PCR resulting in a low coefficient of variance, high reproducibility, and large sample capacity is possible using optimal internal standardization and the liquid-phase hybridization/ELISA system for detection. The optimized PCR procedure indicated downregulation of atrial AT1 in end-stage human heart failure, suggesting a reduced capacity of the atria to respond to angiotensin II stimulation in end-stage heart failure.
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PMID:Reduced atrial angiotensin receptor type 1 mRNA content in end-stage human heart failure: assessment by a novel quantitative PCR-ELISA technique. 887 58

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.
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PMID:Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure. 892 17


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