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)

In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York Heart Association (NYHA) classification II-III, due to ischemic cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan intravenously (i.v.). Pimobendan progressively reduced systemic resistance and left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and improved isovolumetric contractility and relaxation parameters by 30% (all p < 0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) decreased significantly by 20 and 19%, respectively. Cardiac output (CO) increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change coronary hemodynamics, but myocardial O2 extraction and consumption were decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin II (AII), and aldosterone levels did not change significantly. In contrast, arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 60 min after pimobendan administration. Simultaneously, cardiac renin uptake at baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had progressive positive inotropic and lusitropic effects, diminished preload and afterload despite modest stimulation of plasma renin activity (PRA), and reduced systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a novel calcium-sensitizing compound, in patients with mild to moderate heart failure. 753 50

The purpose of this study was to find the major determinants of survival and nonsurvival after intraaortic balloon pump (IABP) support. One hundred twenty-nine consecutive patients with IABP support from January 1988 to January 1992 were analyzed retrospectively. Differences between the survival and nonsurvival groups were tested with the Student's t test, chi-squared test, and frequency analysis. The overall survival rate was 50.4% (65 of 129). Nonsurvivors (64 of 129, 49.6%) had higher rates of chronic heart failure (21.9% vs 9.2%, p < 0.05), acute myocardial infarction (53.1% vs 24.6%, p < 0.01), cardiomyopathy (9.4% vs 1.5%, p < 0.05), New York Heart Association functional class IV (51.6% vs 13.9%, p < 0.01), and depressed left ventricular ejection fraction (29.38% +/- 8.99% vs 42.88% +/- 5.24%, mean +/- SD, p < 0.01). The nonsurvival group also had longer duration of cardiopulmonary bypass (115.80 +/- 24.43 vs 78.34 +/- 3.81 min, mean +/- SEM, p < 0.02) and aortic occlusion (57.55 +/- 13.03 vs 41.00 +/- 2.79 min, mean +/- SEM, p < 0.05) than the survival group. The major determinants of death after IABP are acute myocardial infarction, left ventricular ejection fraction < 30%, New York Heart Association functional class IV, and longer duration of cardiopulmonary bypass and aortic occlusion. IABP is effective in sustaining hemodynamics, but severe myocardial pump failure portends a poor treatment outcome.
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PMID:Major determinants of survival and nonsurvival of intraaortic balloon pumping. 757 96

The 9-minute self-powered treadmill test has been employed to evaluate submaximal exercise capacity in heart failure patients, but its relation to maximal exercise capacity and to indexes of skeletal muscle function has not been well defined. Two protocols were utilized. The first evaluated the relation of the peak oxygen uptake (VO2) achieved on the self-powered treadmill to that during a symptom-limited treadmill protocol, and examined the reproducibility of this test. Thirteen patients (aged 62 +/- 2 years, in New York Heart Association class I to III [2.3 +/- 0.1], ejection fraction 23 +/- 2% [means +/- SEM]) and 10 age-matched sedentary controls were studied. The second protocol, which involved 18 patients (aged 65 +/- 2 years, in New York Heart Association class I to IV [2.4 +/- 0.1], ejection fraction 23 +/- 2%) and 10 age-matched controls evaluated the relation of performance on the self-powered treadmill to maximal systemic exercise capacity on a cycle ergometer and to indexes of skeletal muscle function. In the first protocol, the test was found to be highly reproducible. The proportion of self-powered treadmill to maximal treadmill peak VO2 did not differ significantly between patients and controls (95 +/- 5% vs 87 +/- 6%). In the second protocol, patients achieved a lower peak VO2 (15.6 +/- 1.1 vs 25.6 +/- 0.9 ml/kg/min, p < 0.001), walked a shorter distance on the self-powered treadmill (367 +/- 32 vs 667 +/- 28 m, p < 0.001), and exhibited less knee extensor work capacity (1,075 +/- 116 vs 1,390 +/- 110 ft-lbs, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of the nine-minute self-powered treadmill test to maximal exercise capacity and skeletal muscle function in patients with congestive heart failure. 757 56

A previous uncontrolled study suggested that nasal continuous positive airway positive airway pressure (NCPAP) may improve left ventricular ejection fraction (LVEF) in patients with congestive heart failure (CHF) and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In order to more critically evaluate the effects of NCPAP on cardiac function, we undertook a randomized, controlled trial of NCPAP in 29 patients with heart failure and CSR-CSA over a 3-mo period, with LVEF as the primary outcome measure. Patients with CHF and associated CSR-CSA who were receiving optimal medical therapy were randomly assigned to a control group (n = 15) or a group receiving nightly NCPAP (n = 14). Twelve patients in each group completed the study. There was a greater improvement of LVEF in the NCPAP group than in the control group during the study (mean +/- SEM = 7.7 +/- 2.5 versus - 0.5 +/- 1.5%, p = 0.019). In addition, there was a significantly greater reduction in the number of apneas and hypopneas (-28.5 +/- 3.9 versus -6.1 +/- 7.0 per hour of sleep, p = 0.012) in the NCPAP group than in the control group. Significantly greater improvements in symptoms of fatigue (5.6 +/- 1.2 versus 0.8 +/- 0.7, p = 0.005) and disease mastery (3.6 +/- 1.1 versus -0.7 +/- 0.7, p = 0.031) were also observed in the NCPAP group. We conclude that in patients with chronic heart failure and CSR-CSA, nightly administration of NCPAP can attenuate CSR-CSA, improve cardiac function, and alleviate symptoms of heart failure.
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PMID:Treatment of congestive heart failure and Cheyne-Stokes respiration during sleep by continuous positive airway pressure. 781 79

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.
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PMID:Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group. 784 53

The interactions of the systemic adaptations during and after rapid ventricular pacing, a model of heart failure, were assessed in conscious, unstressed dogs. One week of ventricular tachycardia (260 beats/min) significantly reduced mean +/- SEM cardiac output (2.3 +/- 0.1 to 1.2 +/- 0.1 liter/min), mean arterial pressure (119 +/- 3 to 93 +/- 3 mm Hg), renal blood flow (168 +/- 19 to 96 +/- 9 ml/min), sodium excretion (36 +/- 5 to 10 +/- 4 mEq/d), increased left and right atrial pressures (8 +/- 1 to 21 +/- 1 and 4 +/- 0 to 11 +/- 1 mm Hg, respectively), plasma atrial natriuretic peptide concentration (24 +/- 4 to 141 +/- 38 fmol/ml), plasma cyclic GMP concentration (9 +/- 1 to 16 +/- 4 pmol/ml), and urinary cyclic GMP excretion (0.77 +/- 0.05 to 2.18 +/- 0.34 nmol/min). These changes persisted throughout 3 weeks of pacing. Gradual increases in systemic and renal vascular resistances (to 122 +/- 17 and 1.30 +/- 0.22 mm Hg/liter/min, respectively) and reductions in glomerular filtration rate (65 +/- 6 to 44 +/- 4 ml/min) reached significance during the third week. Resumption of sinus rhythm stimulated a brisk natriuresis and a return of cardiac output, systemic vascular resistance, and hormone concentrations to control values within 7 days. However, increases of left and right atrial pressures (14 +/- 2 and 8 +/- 1 mm Hg, respectively) were still present after 2 months of recovery. In conclusion, persistent increases in cardiac filling pressures were induced by rapid ventricular pacing in conscious, unstressed dogs, whereas the systemic hemodynamic, renal, and hormonal responses were largely reversible during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, renal, and hormonal effects of rapid ventricular pacing in conscious dogs. 784 52

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.
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PMID:Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study. 794 49

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

The present study evaluates 3H-ouabain binding site (Na,K-ATPase) concentration in left ventricular myocardium of dogs with heart failure induced by tachycardia as a result of ventricular pacing. Samples of left ventricle were obtained from 10 dogs exposed to pacing of 240 beats/min for 3 to 4 weeks and eight sham-operated controls. Na,K-ATPase was quantified using vanadate facilitated 3H-ouabain binding to intact samples. At time of sacrifice paced dogs showed clinical signs of heart failure, a significant 257% increase in left ventricular end diastolic pressure and a significant 46% decrease in left ventricular dP/dt compared with control. There was no significant change in left ventricular mass. 3H-ouabain binding concentration was significantly reduced by 16%. Evaluation of 3H-ouabain binding kinetics revealed no significant difference between myocardium from paced and control dogs: Equilibrium binding conditions were at the various concentrations used obtained after similar incubation time; nonspecific uptake and retention of 3H-ouabain was 0.9-0.8% of total uptake and retention obtained in the standard assay; apparent dissociation constant (KD) was 6.5 x 10(-8)-6.6 x 10(-8) mol/l; loss of specifically bound 3H-ouabain during washout at 0 degrees C occurred with a half-life time (T1/2) of 120 and 121 h. Hence, total 3H-ouabain binding site concentration in left ventricular myocardium was (mean +/- SEM) 1110 +/- 56 and 1317 +/- 68 pmol/g wet weight, 8.54 +/- 0.43 and 10.05 +/- 0.52 pmol/mg protein, and the total amount of 3H-ouabain binding sites in the entire left ventricle 121 +/- 6 and 162 +/- 8 nmol in paced (n = 10) and control (n = 8) dogs (p < 0.05), respectively. In conclusion, the present study reports a significant reduction in left ventricular myocardium 3H-ouabain binding site concentration in tachycardia induced heart failure. This observation supports the concept of a relationship between Na,K-ATPase concentration and contractile capacity and may be of pathophysiological importance in tachycardia and heart failure.
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PMID:Reduced 3H-ouabain binding site (Na,K-ATPase) concentration in ventricular myocardium of dogs with tachycardia induced heart failure. 814 25

The sympathetic nervous system is activated in acute myocardial infarction (MI). Scarce data exist, however, regarding the release of the sympathetic cotransmitter neuropeptide Y (NPY) during the acute and early convalescent phases after acute MI. Plasma NPY determination was obtained on days 1 and 3 after admission from 47 patients with acute MI and from eight control patients with acute chest pain without MI. Samples were also obtained on day 30 from the 39 survivors from the original MI cohort. Plasma NPY peaked on day 3 in the MI group (day 1: mean = 46.0 pmol/L, SEM = 6.4 pmol/L; day 3: mean = 60.8 pmol/L, SEM = 5.7 pmol/L; day 30: mean = 27.2 pmol/L, SEM = 4.1 pmol/L; days 1 to 3: p = 0.002; days 3 to 30: p < 0.001), whereas in the control group a nonsignificant decrease from day 1 (mean = 42.6 pmol/L, SEM = 12.3 pmol/L) to day 3 (mean = 34.0 pmol/L, SEM = 5.6 pmol/L) was observed. Plasma NPY levels were significantly increased in patients with MI on day 3 (p = 0.044), but not at baseline compared with the control group. No significant association between plasma NPY and plasma catecholamines, clinical heart failure, or 1-month survival was evident. These results suggest that increased plasma levels of the vasoconstrictory and cardiodepressant sympathetic neurotransmitter NPY are present in the recovery phase of MI, but with a plasma profile distinct from that of catecholamines.
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PMID:Plasma neuropeptide Y levels in the acute and early convalescent phase after myocardial infarction. 815 14


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