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)

Angiotensin converting enzyme inhibitors have greatly improved the treatment of patients with chronic heart failure but they are not effective in all patients, and their use may be limited by side effects. There is, therefore, a need to investigate new drugs and to compare their efficacy with angiotensin converting enzyme inhibitors. Flosequinan is a new direct-acting vasodilator that has been shown to be effective in placebo-controlled studies. Patients with chronic heart failure in NYHA classes II or III who remained symptomatic despite at least 80 mg of frusemide daily were recruited from two centers. Following a single-blind placebo run-in period, the patients were randomized double blind to either the addition of captopril or flosequinan for 6 weeks. Following a further 2-week placebo washout period, they were then given the alternative treatment. Symptom-limited treadmill exercise times, scores of perceived exertion, and corridor walk tests were measured at two weekly intervals during the study. Twenty-five patients entered the study, 16 of whom completed without a change in diuretic dose. Five patients were withdrawn while taking captopril and two while taking flosequinan; two were withdrawn during the placebo washout period. For those patients who completed the study, flosequinan increased treadmill exercise tolerance from a mean (SEM) placebo time of 11.5 (1.0) minutes by 2.4 (0.6) (p = 0.0002) and captopril from 12.0 (0.8) minutes by 1.2 (0.6) minutes (p = 0.08). Comparison of the other measures of efficacy revealed no difference between the groups. In this short-term study flosequinan appeared to be equal in efficacy to captopril.
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PMID:A comparison of the effects of captopril and flosequinan in patients with severe heart failure. 145 90

To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.
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PMID:Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure. 146 37

Clentiazem, 8-chloro diltiazem, is a calcium channel blocker currently undergoing evaluation for the treatment of stable angina and hypertension. As patients with ischaemic disorders often present some degree of heart failure, the aim of this study was to investigate the effect of congestive heart failure on clentiazem (200 micrograms kg-1, i.v. bolus) pharmacokinetics in a canine model. Congestive heart failure was induced in six dogs by rapid ventricular pacing (240 beats min-1) for 3-5 weeks. Clentiazem pharmacokinetics was studied in each dog under the control condition and after the development of clinical signs of heart failure (ascites, dyspnea, fatigue). Blood samples were collected up to 480 min post-dose. Clentiazem plasma concentrations were determined by high performance liquid chromatography. The area under the plasma concentration versus time curves (AUC0-infinity) was significantly increased in congestive heart failure dogs (8.8 +/- 1.6 vs 21.8 +/- 1.4 micrograms min ml-1) (mean +/- SEM). These changes were related to a reduction of the volume of distribution of the central compartment (0.9 +/- 0.1 vs 0.2 +/- 0.11 kg-1) and total body clearance (1.9 +/- 0.4 vs 0.7 +/- 0.21 h-1 kg-1). It is concluded that, in our model, congestive heart failure significantly modifies clentiazem disposition. These results suggest that caution should be exercised when clentiazem is given to patients with a low ejection fraction and a compromised cardiac function. Reduced loading and maintenance doses might be recommended in patients with severe congestive heart failure.
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PMID:Effect of congestive heart failure on clentiazem pharmacokinetics in a dog model. 148 42

Skeletal muscle powered assist ventricles (SMV) are being investigated in animal studies as a treatment for heart failure. Muscle fatigue is almost always dependent upon muscle capillary blood flow. This study examined the relationship between SMV intrapouch pressure and blood flow to the circumferential muscle in a working SMV with a mock circulation. The unconditioned rectus abdominis muscle was used to create an in situ SMV in five dogs. Muscle blood flow was measured by both the radioactive microsphere and the electromagnetic flow probe method as the pouch pressure was varied between 10 and 70 mmHg and as the SMV was stimulated to contract at a rate of 20 min-1. The correlation coefficient for the two methods was 0.908. At pouch pressures of 10, 40, and 70 mmHg, the respective blood flow values were 22.60 +/- 2.50 (1 SEM), 12.20 +/- 2.10, and 4.40 +/- 0.74 ml min-1 (p less than 0.05). When they were corrected for muscle weight, the mean blood flow values at these same pouch pressures were 0.28 +/- 0.03, 0.15 +/- 0.03, and 0.05 +/- 0.01 ml min-1 g-1, respectively (p less than 0.05). SMV output was measured for each pouch pressure that was tested. Pouch output, expressed as ml min-1, was 458 +/- 20 (1 SEM) at an SMV diastolic pouch pressure of 10 mmHg, 309 +/- 22 at a pouch pressure of 40 mmHg, and 103 +/- 6 at a pouch pressure of 70 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of skeletal muscle ventricle pouch pressure on muscle blood flow. 153 16

Cine nuclear magnetic resonance (NMR) imaging was used to serially measure cardiovascular function in 17 patients with New York Heart Association class II or III heart failure and left ventricular ejection fraction less than or equal to 45% who were treated for 3 months with benazepril hydrochloride, a new angiotensin-converting enzyme inhibitor, while continuing treatment with diuretic agents and digoxin. Interobserver reproducibilities for ejection fraction (r = 0.94, SEE 3.3%), end-systolic volume (r = 0.98, SEE 10.6 ml), end-diastolic volume (r = 0.99, SEE 8.29 ml), end-systolic mass (r = 0.96, SEE 15.4 g), end-systolic wall stress (r = 0.91, SEE 10 dynes.s.cm-5) and end-systolic stress/volume ratio (r = 0.85, SEE 0.13) demonstrated applicability of cine NMR imaging for the serial assessment of cardiovascular function in response to pharmacologic interventions in patients with heart failure. During 12 weeks of treatment with benazepril, ejection fraction increased progressively from 29.7 +/- 2.2% (mean +/- SEM) to 36 +/- 2.2% (p less than 0.05), end-diastolic volume decreased from 166 +/- 14 to 158 +/- 12 ml (p = NS), end-systolic volume decreased from 118 +/- 12 to 106 +/- 11 ml (p less than 0.05), left ventricular mass decreased from 235 +/- 13 to 220 +/- 12 g (p less than 0.05), end-systolic wall stress decreased 29% from 90 +/- 5 to 64 +/- 5 dynes.s.cm-5 (p less than 0.05), end-systolic pressure decreased from 92.6 +/- 3.7 to 78.8 +/- 5.3 (p less than 0.05) and end-systolic stress/volume ratio, a load-independent index of contractility, decreased from 0.83 +/- 0.05 to 0.67 +/- 0.06 (p less than 0.05), demonstrating that improved ejection fraction is due to afterload reduction.
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PMID:Application of cine nuclear magnetic resonance imaging for sequential evaluation of response to angiotensin-converting enzyme inhibitor therapy in dilated cardiomyopathy. 156 30

To investigate the influence of the presence of oedema on the pharmacokinetics and pharmacodynamics of furosemide (frusemide) we selected 9 hospitalised patients (mean age 70.3 years, range 59 to 84 years) with severe congestive heart failure (NYHA III to IV) and an assessed amount of peripheral oedema of at least 5 kg. In these patients the absorption of a single oral dose of furosemide 250 mg was studied when their heart failure was decompensated and again, after intensive therapy, when it was clinically compensated. The mean (+/- SEM) weight loss after clinical treatment was 12.0 +/- 2.2 kg. Individual furosemide plasma concentration-time curves could be fitted adequately to a 1-compartment model with 1 first-order absorption and elimination process, in which absorption took place in 2 parts with different lag times. Comparing the decompensated state with the compensated state we did not find significant differences in pharmacodynamics, absorption half-life, elimination half-life, time to peak serum concentration, peak serum concentration itself and area under the plasma concentration-time curve. However, the relative amount of furosemide absorbed in the first fraction was significantly increased after compensation. We conclude that the presence of massive oedema in patients with congestive heart failure has a minor influence on the pharmacokinetics and pharmacodynamics of high dose oral furosemide.
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PMID:Absorption of high dose furosemide (frusemide) in congestive heart failure. 160 90

A total of 12 patients (mean age +/- SEM 63 +/- 2.6 years) with moderate to severe heart failure (ejection fraction = 23 +/- 3.2%) were included in a placebo-controlled crossover trial. Patients were randomly allocated to 4 periods of 6 weeks each: placebo, placebo and physical training, lisinopril 10 mg daily, and lisinopril and physical training. The exercise time increased from 13.6 +/- 0.9 min with placebo to 15 +/- 1 min with training alone, and to 16.1 +/- 0.7 min with lisinopril and training. With lisinopril alone there was a non-significant increase in exercise time, to 14.5 +/- 0.6 min. Improvements in exercise time were accompanied by a similar increase in peak oxygen consumption. Overall, the most significant improvements in symptoms and indices of cardiorespiratory fitness were achieved with a combination of lisinopril and training. Thus physical training is not only a useful adjunct to the existing medical therapy for heart failure, but it may also provide symptomatic benefits in its own right.
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PMID:Angiotensin-converting enzyme inhibition and physical training in heart failure. 835 88

Severe decompensated chronic heart failure is associated to increased levels of circulating catecholamines and decreased density of myocardial beta-adrenergic receptors. In 14 patients with stable, class II-III heart failure we studied circulating lymphocytes to determine the number of beta adrenergic receptors, the dissociation constant of 3H dihydroalprenolol (kd) and the intracellular content of cyclic AMP (AMPc). Results (mean +/- SEM) were compared to those obtained in 10 healthy controls. The number of beta receptors was significantly decreased (105 +/- 16 vs 185 +/- 24, fmol/mg of membrane protein, p less than 0.01). No differences were found in Kd (1.65 +/- 0.2 vs. 1.36 +/- 0.28 nm) nor the level of AMPc (7.9 +/- 2.1 vs 7.1 +/- 2.9 pmol/mg protein), respectively. The decreased number of beta adrenergic receptors in the circulating lymphocytes may be related to the increased level of circulating catecholamines that have been shown to be present during exercise in these patients.
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PMID:[Beta adrenergic receptors in circulating lymphocytes of patients with chronic heart failure]. 166 48

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of heart failure on baroreflex control of sympathetic neural activity. 146 51

Plasma concentrations of atrial natriuretic peptide and aldosterone and plasma renin activity were measured in patients with peripartum heart failure and in age matched healthy women post partum. Both groups had carried out traditional postpartum practices of salt consumption and body heating. Plasma concentrations (mean (SEM)) of atrial natriuretic peptide were significantly higher in the seven patients with peripartum heart failure (146.9 (24.3) pg/ml) than in the seven controls (4.4 (0.8) pg/ml). Both plasma aldosterone and plasma renin activity were suppressed in the patients with peripartum heart failure. After treatment for the heart failure plasma atrial natriuretic peptide fell considerably and there were associated increases in plasma aldosterone and plasma renin activity. The high plasma concentrations of atrial natriuretic peptide may have been a compensatory response to salt and water retention as well as to the heart failure. These high concentrations could also, in part, have suppressed the release of aldosterone and renin in an attempt to correct for volume overload.
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PMID:Atrial natriuretic peptide, aldosterone, and plasma renin activity in peripartum heart failure. 182 4


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