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)

Many newly developed positive inotropic agents are phosphodiesterase inhibitors. In the heart at least four phosphodiesterases (PDE I-IV) have been isolated. Depending on the species investigated, the positive inotropic effects of the PDE inhibitors appear to be correlated to the inhibition of a soluble or particulate PDE III or to a particulate PDE bound to the sarcoplasmic reticulum. In human ventricular tissue isolated from hearts with end-stage heart failure due to idiopathic dilated cardiomyopathy the positive inotropic effect of phosphodiesterase inhibitors is greatly reduced compared to healthy controls. This cannot be explained by an impaired sensitivity of the PDEs because the PDEs were similarly inhibited by PDE inhibitors in both healthy and diseased hearts. However, because the reduced positive inotropic effect is accompanied by a reduced increase in cellular cAMP concentration, an impaired formation of cAMP by the adenylate cyclase is probably involved. The impaired adenylate cyclase activity can result from an increased inhibitory GTP-binding protein (Gi-protein) recently observed in failing hearts.
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PMID:Phosphodiesterase inhibition and positive inotropic effects. 247 97

The present multicenter open investigation was designed to provide information on the adverse reaction rate, drug interaction, and survival in a group of 544 cardiac patients treated for 1 year with ibopamine either alone or in association with digitalis, diuretics, and other drugs. Some efficacy parameters were also considered. Heart failure was due to idiopathic dilated cardiomyopathy (21%), ischemic heart disease (32%), hypertensive heart disease (31%), and others (16%). Ibopamine was given alone to 39 patients; the others were given the drug in association with digitalis, diuretics, and vasodilators. One hundred forty patients did not complete the trial (25.7%). The most common causes of discontinuation were death (12.5%), noncompliance with the protocol (5%), and adverse events (3.9%). The clinical conditions and NYHA functional class improved in most patients. The cardiothoracic ratio decreased on average. The 1-year mortality rates associated with NYHA class II, III, and IV were 4.4, 13.8, and 37.2%, respectively. Survival tended to be shorter in a small group of 22 patients with hyponatremia, thus confirming some previous reports. Adverse experiences were mainly related to cardiovascular and gastrointestinal systems; the symptoms were considered severe only in 1 of 544 patients enrolled. Ibopamine seems not to induce dangerous arrhythmias. Blood pressure and heart rate did not change over time during ibopamine treatment. Laboratory tests were not significantly affected; fluctuations observed in some tests were related to concomitant variations in the severity of the primary disease. No tolerance to ibopamine seems to be observed during this long-term therapeutic trial.
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PMID:Long-term therapy of chronic congestive heart failure with ibopamine: a multicenter trial. 248 46

Phosphodiesterase inhibitors have vasodilating and positive inotropic properties, and these compounds may have energy saving effects due to vasodilation and energy consuming effects due to inotropism. In order to differentiate between the effects, it is necessary to relate myocardial oxygen consumption to its hemodynamic determinants. Myocardial oxygen consumption per beat was related to the following parameters: dp/dtmax, mean velocity of fiber shortening, pressure-volume work, peak developed wall stress, and stress-time integral. The best linear relationship was found between myocardial oxygen consumption per beat and the corresponding stress-time integral (r = 0.71; p less than 0.001) in patients with idiopathic dilative cardiomyopathy. Using i.v. nitroprusside as a pure vasodilator, myocardial oxygen consumption per beat and stress-time integral decreased along this established relationship. In contrast, the phosphodiesterase inhibitor enoximone given intravenously decreased the stress-time integral significantly more than the myocardial oxygen consumption per beat. We conclude from these data that phosphodiesterase inhibitors possess vasodilating properties which reduce the myocardial oxygen demand. In addition, they do have positive inotropic effects which increase the myocardial oxygen demand. Myocardial oxygen consumption always reflects the sum of both effects. The balance between the energy saving and the energy consuming effects may determine the efficacy of phosphodiesterase inhibitors, especially in the long-term treatment of chronic heart failure.
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PMID:Separation between vasodilation and positive inotropism by assessment of myocardial energetics in patients with dilated cardiomyopathy. 253 Sep 75

Cardiac beta-adrenoceptor density and subtype distribution has been determined in different kinds of heart failure. A decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure. However, cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected in different kinds of heart failure: while in end-stage idiopathic dilated cardiomyopathy the diminished cardiac beta-adrenoceptor function is due to a selective loss in beta 1-adrenoceptors, in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy it is characterized by a concomitant reduction in beta 1- and beta 2-adrenoceptors. Chronic treatment of heart failure patients with beta-adrenoceptor antagonists leads to an up-regulation of cardiac beta-adrenoceptors, but in a subtype-selective fashion: beta 1-selective antagonists increase only cardiac beta 1-adrenoceptors, whereas non-selective antagonists increase both beta 1- and beta 2-adrenoceptors. Such a (subtype-selective) 'recovery' of cardiac beta-adrenoceptors may be one reason for the beneficial effects of low-dose beta-adrenoceptor antagonist treatment in patients with severe heart failure.
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PMID:Drug- and disease-induced changes of human cardiac beta 1- and beta 2-adrenoceptors. 255 10

T-cell subsets were measured in the peripheral blood of 33 patients with heart failure from idiopathic dilated cardiomyopathy, 22 patients with heart failure from other causes, and 33 normal controls. Mean T-suppressor cell percentage was 30% in normals, 21% in patients with idiopathic dilated cardiomyopathy whose duration of symptoms was less than 1 year (P = 0.0005), and 26% in those with symptoms for greater than 1 year (P = 0.05). Similarly, percentage of T-suppressor cells in the group with heart failure from causes other than idiopathic dilated cardiomyopathy was significantly lower (23%; P = 0.005) in those with short duration of symptoms. When both heart failure groups were combined those with symptoms for less than 1 year had significantly lower T-suppressor frequencies (22%) than those with symptoms for more than 1 year (P = 0.015). Multivariate analysis identified duration of symptoms and age as the only independent predictors of T-suppressor cell frequencies. Decreased percentage of T-suppressor cells in patients with idiopathic dilated cardiomyopathy may be an epiphenomenon related to duration of heart failure. This should be taken into account in assigning an etiologic mechanism for T-suppressor cells in idiopathic dilated cardiomyopathy.
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PMID:T-lymphocyte subsets in patients with idiopathic dilated cardiomyopathy. 256 79

Natural history and prognostic factors in chronic congestive heart failure were investigated in 141 patients (100 males and 41 females), aged 58 +/- 14.5 years, who were hospitalized between 1981-1985. Heart failure was due to idiopathic dilated cardiomyopathy in 79 patients and ischemic heart disease in 62 patients. The following parameters were examined: sex, age, etiology, NYHA functional class, mean arterial blood pressure, heart rate, presence of 3rd heart sound, atrial fibrillation and left ventricular conduction delay, plasma sodium, echocardiographic shortening fraction, and treatment with vasodilators. Mean follow-up was 31 +/- 19 months. Overall survival was 83% at 1 year, 58% at 3 years and 49% at 5 years. No difference in mortality was evident between the two etiological groups, while the data on the cause of death showed a significant difference: sudden death was prevalent in the patients with ischemic disease (50% vs 24%), intractable heart failure predominated in patients with idiopathic dilated cardiomyopathy (69.7% vs 42.8%) (p less than 0.05). The multivariate analysis with the Cox model resulted in a negative prognostic significance of the male sex (p less than 0.02), III and IV NYHA functional class (p less than 0.04), heart rate at rest greater than 85 b/min (p less than 0.002) and the presence of left ventricular conduction delay on standard ECG (p less than 0.001).
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PMID:[Clinical characteristics and prognostic factors in chronic heart failure secondary to primary dilated cardiomyopathy and ischemic heart disease]. 274 8

Multivariate analysis was used to analyze the morphometric data of endomyocardial biopsies (area, perimeter and minor diameter) of myocardial cells obtained at light microscopy by a computerized approach with 16 clinical parameters and prognosis in 52 patients with idiopathic dilated cardiomyopathy. The best morphometric parameter was "area" (R2 = 0.47). A positive correlation was found with age (p less than 0.02), interval between first symptoms and diagnosis (p less than 0.02), left ventricular end-diastolic volume (p less than 0.02), cardiac index (p less than 0.05) and echocardiographic end-diastolic diameter (p less than 0.1). A negative correlation was found with prognosis (p less than 0.02), ejection fraction (p less than 0.02), shortening fraction (p less than 0.05), echocardiographic end-systolic diameter (p less than 0.06) and mitral regurgitation presence (p less than 0.1). The parameters that provided no correlation were New York Heart Association class, left ventricular end-diastolic pressure, right atrial pressure, cardiothoracic ratio, presence or absence of heart failure, fever or alcohol intake. These findings suggest that endomyocardial biopsy may provide prognostic information and confirm clinical diagnosis.
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PMID:Correlation between histomorphometric findings on endomyocardial biopsy and clinical findings in idiopathic dilated cardiomyopathy. 277 94

The contractile response and myocardial content of Gi-proteins were examined in cardiac preparations from explanted hearts of four different patients with end-stage heart failure. Three patients had idiopathic dilated cardiomyopathy and one patient had inflammatory heart disease. Preparations from patients with idiopathic dilated cardiomyopathy showed reduced contractile response to the cAMP-increasing agent isoprenaline and an increase in myocardial Gi-proteins, compared with preparations from non-failing hearts. Therefore it is conceivable that an increase in myocardial Gi-proteins is causally related to heart failure due to idiopathic dilated cardiomyopathy. In the preparation from the patient with inflammatory heart disease the contractile response to isoprenaline was not reduced and likewise content of Gi-proteins was not changed.
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PMID:Increase in myocardial Gi-proteins in heart failure. 290 84

A double-blind, randomized, crossover trial was undertaken to compare the effect of enoximone (150 mg, 3 times daily) and captopril (25 mg, 3 times daily) added to conventional therapy with diuretics in the treatment of 13 patients with severe chronic heart failure. Each treatment was continued for 1 month. Heart failure was due to idiopathic dilated cardiomyopathy in 6 patients and coronary artery disease in 7. Hemodynamic measurements were made at rest and during exercise, on entry to the study and after each treatment period. The cardiac index at rest was 1.9 +/- 0.2 liters min-1 m2 (mean +/- 1 standard deviation) and did not change with either drug. Systemic vascular resistance at rest decreased with enoximone (p less than 0.05) and was unchanged with captopril. Systemic vascular resistance at peak exercise was not lowered by either drug. Both drugs caused an increase of cardiac index at peak exercise (p less than 0.04) and a prolongation of exercise time (p less than 0.05). No difference was detected between the hemodynamic response to the 2 drugs after 1 month treatment either at rest or during exercise.
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PMID:A comparison of hemodynamic effects of one-month oral captopril and enoximone treatment for severe congestive heart failure. 295 72

The long-term safety and efficacy of the inotropic/vasodilatory agent enoximone (50 to 100 mg 3 times daily) were evaluated in 30 patients with chronic congestive heart failure (New York Heart Association classes II to IV). Nineteen patients had idiopathic dilated cardiomyopathy and 11 had ischemic heart disease. Patients were receiving maintenance therapy of digitalis and diuretics. Cardiac function was assessed at 12 week intervals (physical examination, exercise testing, chest x ray, echocardiography, radionuclide angiography, 24-hour Holter monitoring and blood chemistry). During a mean follow-up of 40 weeks, 6 patients died, due to noncardiac (n = 1) and sudden death (n = 1) and to cardiac failure (n = 4) within 36 weeks of drug treatment. In the remaining patients New York Heart Association class improved in 18, was stationary in 5 and deteriorated in 1. Exercise capacity increased during the first 26 weeks and was maintained improved thereafter. Clinical improvement appeared not to wane with time. No change in heart rate, blood pressure and cardiothoracic ratio was observed. Echocardiographic left ventricular dimensions did not change significantly; however, the fractional shortening increased from baseline (14%) to 19% after 12 weeks, 17% after 26 weeks and 21% after 52 weeks (p less than 0.05). The preejection period/left ventricular ejection time ratio decreased from 0.74 to 0.35, 0.44 and 0.43 (p less than 0.05), respectively. There was an increase in radionuclide ejection fraction from 23% to 27% (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term treatment with oral enoximone for chronic congestive heart failure: the European experience. 295 76


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