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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies have associated myocardial dysfunction with reduced myocardial Na,K-pump concentration, but whether impaired Na,K-pump capacity is a pathogenetic factor or an epiphenomenon related to accompanying cardiac hypertrophy is not established. We measured Na,K-pump concentrations in 10 hypertrophied and 11 normal weighted hearts obtained at autopsy using [3H]ouabain as ligand. Specific [3H] ouabain binding site concentration (OBC) in the left ventricle (LV) averaged 449 +/- 40 (pmol.g-1 wet weight; mean +/- SEM) in hypertrophied and 598 +/- 36 in normal weighted ventricles (P = 0.02). A trend towards lower LV OBC (-19%; P = 0.25) was found in hypertrophied hearts from patients with congestive heart failure as compared with non-failing hypertrophied hearts. In multivariate analysis with 18 variables including age and heart failure, only LV weight correlated independently with LV OBC (r = -0.61; P = 0.003). When OBC was related to either dry weight or to protein content, a 25-35% reduction was consistently found in hypertrophied LV, whereas RV OBC was similar in both groups. In conclusion, myocardial Na,K-pump concentration and thus the capacity to maintain homeostasis is reduced in LV, but not in RV, of hypertrophied hearts. Whether the moderately reduced myocardial Na,K-pump concentration is a pathogenetic factor in LV dysfunction remains to be determined.
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PMID:Na,K-pump concentration in hypertrophied human hearts. 798 17

(+/-)-Dobutamine is a positive inotropic drug usually used to improve ventricular function in patients with congestive heart failure (CHF). However, it has been found that haemodynamic responses to dobutamine become blunted during continuous treatment. In this study we determined the time-dependent changes of beta-adrenergic receptors in CHF patients treated with dobutamine. Seven CHF patients received a continuous intravenous infusion of dobutamine (5 micrograms.kg-1 x min-1) for 96 h. Blood samples were obtained before and every 24 h after starting the therapy. The density of beta-adrenergic receptors on mononuclear leukocytes and the plasma concentrations of norepinephrine and epinephrine were determined. During dobutamine treatment the receptor density (fmol.mg-1, mean +/- SEM) gradually decreased from 42.8 +/- 4.4 (baseline) to 31.4 +/- 3.3 (P < 0.05), 25.2 +/- 4.0 (P < 0.01), 18.8 +/- 5.5 (P < 0.01) and 13.4 +/- 3.4 (P < 0.01) at 24, 48, 72 and 96 h, respectively. However, the plasma concentrations of norepinephrine and epinephrine were not significantly changed during the 96 h period of treatment. Thus, the beta-adrenergic receptors down-regulated as early as 24 h after the dobutamine treatment was begun in CHF patients. This receptor down-regulation was not associated with changes of plasma catecholamine concentrations, but was related rather to the development of drug tolerance to dobutamine.
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PMID:Down-regulation of beta-adrenergic receptors on mononuclear leukocytes induced by dobutamine treatment in patients with congestive heart failure. 826 81

Periodic breathing with central apneas during sleep is typically triggered by hypocapnia resulting from hyperventilation. We therefore hypothesized that hypocapnia would be an important determinant of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with congestive heart failure (CHF). To test this hypothesis, 24 male patients with CHF underwent overnight polysomnography during which transcutaneous PCO2 (PtcCO2) was measured. Lung to ear circulation time (LECT), derived from an ear oximeter as an estimate of circulatory delay, and CSR-CSA cycle length were determined. Patients were divided into a CSR-CSA group (n = 12, mean +/- SEM of 49.2 +/- 6.3 central apneas and hypopneas per h sleep) and a control group without CSR-CSA (n = 12, 4.9 +/- 0.8 central apneas and hypopneas per h sleep). There were no significant differences in left ventricular ejection fraction, awake PaO2, mean nocturnal SaO2, or LECT between the two groups. In contrast, the awake PaCO2 and mean sleep PtcCO2 were significantly lower in the CSR-CSA group than in the control group (33.0 +/- 1.2 versus 37.5 +/- 1.0 mm Hg, p < 0.01, and 33.2 +/- 1.2 versus 42.5 +/- 1.2 mm Hg, p < 0.0001, respectively). Neither group had significant awake or sleep-related hypoxemia. In addition, CSR-CSA cycle length correlated with LECT (r = 0.939, p < 0.001). We conclude that (1) hypocapnia is an important determinant of CSR-CSA in CHF and (2) circulatory delay plays an important role in determining CSR-CSA cycle length.
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PMID:Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure. 814 43

1. To examine the contribution of paradoxical reflex forearm vasodilatation during unloading of cardiopulmonary baroreceptors to systemic haemodynamics, the responses of central and peripheral haemodynamics during lower-body negative pressure were measured in 24 patients with chronic congestive heart failure (New York Heart Association functional class II-IV) and were compared with those of 10 normal subjects. 2. Lower-body negative pressure of less than -20 mmHg caused a significant forearm vasoconstriction in normal subjects but not in patients with congestive heart failure. In the individual cases, however, eight patients (subgroup A) had a significant forearm vasoconstriction, whereas 10 patients (subgroup B) had a paradoxical forearm vasodilatation. The remaining six patients had a blunted forearm vascular response. Baseline pulmonary capillary wedge pressure (26 +/- 3 versus 20 +/- 1 mmHg, means +/- SEM) and left ventricular wall stress in end-diastole (57 +/- 6 versus 37 +/- 4 g/cm2) were significantly (P < 0.05) higher in subgroup B than in subgroup A. 3. During lower-body negative pressure of -20 mmHg, the plasma level of noradrenaline, systemic vascular resistance and cardiac index did not change significantly in subgroup A. In subgroup B, however, during this orthostatic stimulus systemic vascular resistance fell significantly from a baseline value of 2023 +/- 109 to 1740 +/- 110 dyn s-1 cm-5 (P < 0.01) and cardiac index increased significantly from a baseline value of 2.0 +/- 0.1 to 2.5 +/- 0.2 1 min-1 m-2 (P < 0.01) despite there being no significant change in the plasma level of noradrenaline. 4. After treatment, a second bout of lower-body negative pressure was applied to seven patients in subgroup B. The forearm vascular response to the second bout of lower-body negative pressure was normalized. 5. These data suggest that the patients with more severe heart failure show a paradoxical forearm vasodilatation during mild lower-body negative pressure and that this altered cardiopulmonary baroreflex control of the circulation serves to improve the depressed cardiac performance.
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PMID:Paradoxical forearm vasodilatation and haemodynamic improvement during cardiopulmonary baroreceptor unloading in patients with congestive heart failure. 838 49

Patients with congestive heart failure (CHF) suffer from respiratory muscle weakness which may contribute to dyspnea. Nasal continuous positive airway pressure (NCPAP) can improve left ventricular ejection fraction (LVEF) and reduce dyspnea in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) but its effects on respiratory muscle strength are not known. We therefore studied the effects of NCPAP on maximal inspiratory and expiratory pressures (MIP and MEP, respectively), LVEF, dyspnea, and fatigue in patients with chronic CHF and CSR-CSA over 3 mo. Eight patients were randomized to control and nine to nightly NCPAP. There were no significant changes in any of these factors in the control group during the study. In contrast, among the NCPAP group, MIP increased from 79.3 +/- 8.1 to 90.7 +/- 10.4 cm H2O (mean +/- SEM; p < 0.02), LVEF increased from 24.0 +/- 4.0 to 32.6 +/- 6.6% (p < 0.02) and symptoms of dyspnea and fatigue were alleviated. However, MEP did not change. In addition, the number of apneas and hypopneas decreased from 49 +/- 11 to 17 +/- 7 per hour of sleep (p < 0.001) and mean low Sao2 during sleep increased from 87.9 +/- 1.0 to 93.0 +/- 1.0% (p < 0.01). Our data indicate that nightly application of NCPAP in patients with CHF and CSR-CSA improves inspiratory muscle strength and LVEF, and relieves dyspnea and fatigue.
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PMID:CPAP improves inspiratory muscle strength in patients with heart failure and central sleep apnea. 854 29

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.
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PMID:Plasma adrenomedullin concentration in patients with heart failure. 855 Jul 49

The renin-angiotensin system is a major contributor to the pathophysiology of cardiovascular diseases such as congestive heart failure and hypertension. Antagonizing angiotensin (Ang) II at the receptor site may produce fewer side effects than inhibition of the promiscuous converting enzyme. The present study was designed to assess in healthy human subjects the effect of LRB081, a new orally active AT1-receptor antagonist, on the pressor action of exogenous Ang II. At the same time, plasma hormones and drug levels were monitored. At 1-week intervals and in a double-blind randomized fashion, 8 male volunteers received three doses of LRB081 (10, 40, and 80 mg) and placebo. Blood pressure (BP) was measured at a finger by photoplethysmograph. The peak BP response to intravenous injection of a standard dose of Ang II was determined before and for < or = 24 h after administration of an oral dose of LRB081 or placebo. After drug administration, the blood BP response to Ang II was expressed in percent of the response before drug administration. At the same time, plasma renin activity (PRA), Ang II, aldosterone, catecholamine (radioassays), and drug levels (by high-performance liquid chromatography) were monitored. After LRB081 administration, a dose dependent inhibition of the BP response to Ang II was observed. Maximal inhibition of the systolic BP response was 54 +/- 3 (mean +/- SEM), 63 +/- 2, and 93 +/- 1% with 10, 40, and 80 mg LRB081, respectively. The time to peak was 3 h for 6 subjects and 4 and 6 h for 2 others. Preliminary plasma half-life (t1/2) was calculated at 2 h. With the highest dose, the inhibition remained significant for 24 h (31 +/- 5%, p < 0.05). Maximal BP-blocking effect and maximal plasma drug level coincided, suggesting that the unmetabolized LRB081 is responsible for the antagonistic effect. PRA and Ang II increased dose dependently after LRB081 intake. Aldosterone, epinephrine, and norepinephrine concentrations remained unchanged. No clinically significant adverse reaction was observed during the study. LRB081 is a well-tolerated, orally active, potent, and long-acting Ang II receptor antagonist. Unlike in the case of losartan, no active metabolite of LRB081 has been shown to be responsible for the main effects.
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PMID:Clinical and hormonal effects of the new angiotensin II receptor antagonist LRB081. 885 81

Previous exercise training studies in patients with chronic congestive heart failure (CHF) were performed for periods lasting > 2 months, and effects of activity restriction on exercise induced-benefits were not systematically assessed. With one exception study, patients were not reported to be transplant candidates. In this random-order crossover study, effects of 3 weeks of exercise training and 3 weeks of activity restriction on functional capacity in 18 hospitalized patients with severe CHF [(mean +/- SEM) age 52 +/- 2 years; ejection fraction 21 +/- 1%; half of them on a transplant waiting list] were assessed. The training program consisted of interval exercise with bicycle ergometer (15 minutes) 5 times weekly, interval treadmill walking (10 minutes), and exercises (20 minutes), each 3 times weekly. With training, the onset of ventilatory threshold was delayed (p < 0.001), with increased work rate by 57% (p < 0.001) and oxygen uptake by 23.7% (p < 0.001). On average, there was a 14.6% decrease in slope of ventilation/carbon dioxide production before the onset of ventilatory threshold (p < 0.05), and ventilatory equivalent of carbon dioxide production by 10.3% (p < 0.01). At the highest comparable work rate (56 +/- 5 W) the following variables were decreased: heart rate (7.3%; p < 0.05), lactate (26.6%; p < 0.001), and ratings of perceived leg fatigue and dyspnea (14.5% and 16.5%; p < 0.001 each). At peak exercise, oxygen uptake was increased by 19.7% (p < 0.01) and oxygen pulse by 14.2% (p < 0.01). There was a correlation of baseline peak oxygen uptake and increase of peak oxygen uptake due to training (r = -0.75; p < 0.004). Independently of the random order, data after activity restriction did not differ significantly from data measured at baseline. Patients with stable, severe CHF can achieve significant improvements in aerobic and ventilatory capacity and symptomology by short-term exercise training using interval exercise methods. Impairments due to activity restriction suggest the need for long-term exercise training.
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PMID:Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure. 891 81

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide. 2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l), congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5 pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P < 0.05), confirming previous reports. 4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.
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PMID:Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal disorders. 903 92

We prospectively assessed whether baseline central hemodynamics and exercise capacity can predict improvement of VO2 at ventilatory threshold (VT) after exercise training in patients with severe chronic congestive heart failure. Eighteen patients (mean +/- SEM; age 52 +/- 2 years), half of them listed for transplant, underwent 3 weeks of exercise training (interval cycle and treadmill walking; 5 x/week) and 3 weeks of activity restriction in a random-order crossover trial. Baseline data were not significantly different for groups with exercise training first and activity restriction first: cardiac index at rest (2.1 +/- 0.1 L/m2/min), maximum cardiac index (3.1 +/- 0.2 L/m2/min) (Fick), and echocardiographic ejection fraction (21 +/- 1%). The same was true for cardiopulmonary exercise data (cycle ergometry; up 12.5 W/min): VO2 at VT (9.3 +/- 0.4 ml/kg/min), maximum VO2 (12.2 +/- 0.7 ml/kg/min), VT in percentage of predicted maximum VO2 (31 +/- 2%), heart rate at VT (95 +/- 4 beats/min), and decrease of dead space-to-tidal volume ratio from rest to VT (33 +/- 1 --> 29 +/- 1). Improvement of VO2 at VT after training (2.2 +/- 0.4 ml/kg/min; p <0.001) was not related to baseline central hemodynamics (r = <0.10 for each), but was greater in patients with a lower baseline VO2 at VT (r = -0.65; p <0.01), peak VO2 (r = -0.66; p <0.01), VT in percentage of predicted maximum VO2 (r = -0.74; p <0.001), heart rate at VT (r = -0.63; p <0.01), and smaller decrease of dead space-to-tidal volume ratio from rest to VT (r = 0.65; p <0.01). Ejection fraction after exercise training (24 +/- 2%) and activity restriction (23 +/- 2%) did not differ significantly compared with baseline, and patient status (heart failure and cardiac rhythm) remained stable. Three parameters accounted for 84% of the variance of improvement in VO2 at VT: VO2 at VT in percent predicted maximum VO2, decrease of dead space-to-tidal volume ratio, and heart rate at VT. The findings suggest that there was a greater increase in VO2 at VT after exercise training in patients with greater peripheral deconditioning at baseline. The improvement was unrelated to central hemodynamics. Clinically stable patients with severe chronic congestive heart failure, potential heart transplant candidates, and those awaiting transplantation may benefit from involvement in a short-term exercise training program.
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PMID:Predictors of response to exercise training in severe chronic congestive heart failure. 920 20


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