Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure.
 ...
PMID:Comparison of the haemodynamic effects of dopexamine and dobutamine in patients with severe congestive heart failure. 201 Feb 43

The prolonged noradrenaline treatment of rats (total dosage from 1 week--25 mg/kg), results in greatly reduced cardiac pump function and heart rate with a pronounced increase in left ventricular diastolic stiffness. These functional changes are associated with a deficiency of energy supply, especially depletion of phosphocreatine content. The taurine administration (100 mg/kg prior to 20 min noradrenaline injection) is accompanied by reliably less essential cardiac insufficiency. Moreover, the ATP, ADP level is normal and phosphocreatine content enhances by 15%.
 ...
PMID:[Norepinephrine-induced heart failure and the protective effect of taurine]. 208 93

As many as 59 patients aged 35 to 74 years suffering from mitral valvular disease (MVD) were examined for excretion of dopamine (DA), noradrenaline (NA) and adrenaline, parameters indicating the activity of the sympathoadrenal system. Administration of L-DOPA brought about a significant increase of excretion of all catecholamines in all the patients under 59 years and in those aged 60 to 74 years. In patients with stage I and IIA heart failure, DA excretion rose 50-fold in response to L-DOPA administration, in those with stage IIB and III, 17-fold (p less than 0.001). In patients suffering from MVD, no age-associated differences were revealed in the levels of catecholamines and ICM. In patients suffering from MVD with the predominance of stenosis and in those with stage I and IIA heart failure, background excretion of NA was significantly higher than in patients suffering from MVD with the predominance of heart failure (p less than 0.01). Administration of L-DOPA was followed by an appreciable increment of NA exactly in patients suffering from MVD with the predominance of stenosis (p less than 0.001). In the majority of patients with stage III heart failure refractory to multimodality treatment, the L-DOPA test revealed the smallest increment of DA; its excretion rose only 12-fold. Therefore, the progress of heart failure entails a decrease of the reserve potentialities of the sympathoadrenal system, marked by less output of its mediators.
 ...
PMID:[The sympathetic-adrenal system in mitral heart defects in patients of different ages studied by the use of a specific L-DOPA test]. 209 2

Parameter of catecholamine metabolism were examined in patients (Groups II to V) in chronic, stable stages of coronary heart disease (n = 45), dilated cardiomyopathy (n = 17) and healthy control subjects (Group I). Plasma and urinary catecholamine patterns, catecholamine plasma half-life and catecholamine metabolism following administration of levodopa were determined. In cases of slight (Group II, ejection fraction (EF) 54 +/- 7%) to marked left-heart damage (Group III, EF 44 +/- 5%), the findings indicate elevated catecholamine excretion and a beginning reduction of plasma clearance as the cause of excessive, circulating and renally excreted catecholamines (applies to noradrenaline, less to adrenaline). The renal 24-h dopamine elimination is already slightly reduced in these patients. In cases of severe left-heart damage, the findings are not uniform. In some cases, noradrenaline at rest and at comparable exercise levels are elevated (Group IV, EF 20 +/- 11%), in some cases they are normal (Group V, EF 16 +/- 4%). The 24-h dopamine elimination is reduced in both groups to 34-41% of normal. Noradrenaline and adrenaline elimination is normal, or reduced (Group V, adrenaline). The exercise-induced, maximum plasma noradrenaline concentrations in Group IV and V are much lower (33-40% of normal) than in the healthy control individuals and patients in Groups II and III. Oral administration of 2-4 g levodopa per day result in a 20- to 40-fold dopamine increase in patients with heart failure (Group IV) and healthy control persons (Group I) (free and conjugated plasma dopamine, as well as free urinary dopamine).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Catecholamine metabolism in heart failure patients and healthy control subjects. 209 27

A possible role of the proopiomelanocortin derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has been studied in patients with various degrees of congestive heart failure (CHF). The profile of changes in circulating levels of gamma 2-MSH-like immunoreactivity (-LI) has been compared with those of atrial natriuretic peptide (ANP)-LI, arginine vasopressin (AVP)-LI and catecholamines in CHF. Patients with moderate CHF (New York Heart Association stages I-II) showed significantly higher levels of h-alpha ANP-LI and NA (P less than 0.05) compared to controls. Patients with severe CHF (stages III-IV) had significantly higher levels of all hormones measured compared to controls: noradrenaline, P less than 0.001; adrenaline, P less than 0.001; gamma 2-MSH-LI, P less than 0.001; h-alpha ANP-LI, P less than 0.05; AVP-LI, P less than 0.01. For the catecholamines and gamma 2-MSH-LI there was a significant increase from moderate to severe forms of CHF. A significant correlation was observed between gamma 2-MSH-LI and noradrenaline, and between h-alpha ANP-LI and noradrenaline in patients with CHF. The present results show that gamma 2-MSH-LI is increased only in severe forms of cardiac failure, and that this change is more closely related to the increase in circulating levels of noradrenaline than to increased levels of ANP-LI or AVP-LI.
 ...
PMID:Gamma 2-MSH in congestive heart failure: relation to atrial natriuretic peptide, arginine vasopressin and catecholamines. 213 8

The aim of the present study was to determine whether left atrial size--a likely indicator of atrial stretching--correlates with the plasma concentration of atrial natriuretic peptide and whether this relation is different in patients in sinus rhythm and in those with atrial fibrillation. Arterial plasma concentrations of immunoreactive atrial natriuretic peptide (ir-ANP), adrenaline, noradrenaline, aldosterone, and vasopressin were measured in 13 patients in sinus rhythm without apparent heart failure and in 13 patients in atrial fibrillation. The two groups were matched for left atrial diameter and the ratio of the left atrial diameter to the diameter of the aortic root (assessed by echocardiography). There were no significant differences in age, heart rate, blood pressure, or left ventricular end diastolic diameter between the two groups. Left atrial diameters varied from 33 to 60 mm. The mean (SD) plasma concentration of ir-ANP was significantly higher (35 (21) pmol/l) in the patients with atrial fibrillation than in those in sinus rhythm (12 (11) pmol/l). The concentration of plasma aldosterone was also higher in patients with atrial fibrillation (831 (366) v 523 (211) pmol/l). Concentrations of adrenaline, noradrenaline, and vasopressin were similar in both groups. None of the hormone concentrations correlated with left atrial dimensions. These results indicate that plasma concentrations of ir-ANP and aldosterone are highly sensitive indicators of changes in haemodynamic function during atrial fibrillation. They also underscore the difficulties of correlating echocardiographic assessment of patients with plasma concentrations of a vasoactive hormone.
 ...
PMID:Raised plasma concentrations of atrial natriuretic peptide are independent of left atrial dimensions in patients with chronic atrial fibrillation. 214 16

The addition of enoximone, a phosphodiesterase inhibitor, to adrenergic agents has been found useful in increasing cardiac output in severe heart failure. In one study of 13 patients in cardiogenic shock already receiving adrenergic support, enoximone was administered as a bolus of 0.5 mg/kg over 20 minutes. Pulmonary artery occlusion pressure decreased significantly from 21.7 +/- 5.8 mm Hg to 19.8 +/- 6.0 mm Hg (P less than 0.01) and cardiac index increased markedly. A second study investigated the effects of the addition of small boluses of enoximone to adrenergic agents in low flow states associated with heart failure (n = 8) or postoperative states after cardiac surgery (n = 10). Each of the 18 patients was treated with dobutamine; 12 patients were also treated with dopamine and 4 with noradrenaline. Enoximone was administered as small but increasing intravenous boluses. No significant change in mean arterial pressure was observed, but on 0.5 mg/kg of enoximone pulmonary artery occlusion pressure decreased significantly from 24.6 +/- 8.7 mm Hg to 19.4 +/- 9.9 mm Hg (heart failure) and from 18.2 +/- 3.3 mm Hg to 15.3 +/- 3.8 mm Hg (cardiac surgery) after the initial dose of 0.125 mg/kg. Cardiac index increased markedly after enoximone, 0.25 mg/kg. These changes were significant after the initial dose of 0.125 mg/kg. Thus, the addition of even small doses of enoximone to adrenergic agents can markedly increase cardiac index without significant effect on arterial pressure in medical or surgical cardiac patients.
 ...
PMID:Addition of phosphodiesterase inhibitors to adrenergic agents in acutely ill patients. 214 39

1. Skeletal muscle metabolism in chronic cardiac failure may be influenced by the many circulatory and neurohumoral adaptations in the condition. We investigated aerobic metabolism during exercise using indirect calorimetry in 15 patients with chronic cardiac failure and in 14 control subjects. Subjects exercised on a treadmill for 20 min at a steady-state submaximal workload. 2. Venous lactate levels were relatively constant throughout the exercise, although they were slightly greater in the patients with chronic cardiac failure than in the control subjects. The respiratory exchange ratio was lower in patients with chronic cardiac failure (0.777 +/- 0.021 vs 0.833 +/- 0.037, means +/- SD; P less than 0.0002, Mann-Whitney U-test). Relative fat utilization, expressed as a percentage of total energy expenditure, was therefore greater in patients with chronic cardiac failure (71.8 +/- 7.0 vs 54.1 +/- 12.3%, P less than 0.0005) and this was mirrored in a lower carbohydrate utilization (24.7 +/- 6.5 vs 43.3 +/- 12.1%, P less than 0.0002). Levels of free fatty acids, glycerol and noradrenaline were greater in patients with chronic cardiac failure. 3. We conclude that there is an increased reliance on fat, as opposed to carbohydrate, metabolism during exercise in chronic cardiac failure, and that this may relate to the elevated catecholamine and free fatty acid levels present. This may be a compensatory mechanism to preserve muscle glycogen stores, but as fat utilization is less efficient in terms of oxygen consumed, this shift may further impair exercise capacity.
 ...
PMID:Substrate utilization during exercise in chronic cardiac failure. 216 96

1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume.
 ...
PMID:Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates. 217 9

Low cardiac output in acute heart failure can result in a functional impairment of organs, when tissue hypoxia occurs and cardiogenic shock develops. To restore cardiac output, various forms of therapy can be considered. Fluid replacement is sometimes beneficial in acute situations where oedema can reduce effective plasma volume. Vasodilators are often contra-indicated in shock, when arterial pressure is usually low. Inotropic therapy consists primarily of the administration of adrenergic agents. Dopamine and noradrenaline can be indicated in severe hypotension, to maintain coronary perfusion. Dobutamine is the catecholamine of choice to increase myocardial contractility. However, decreased responsiveness of the myocardial receptors to adrenergic stimulation rapidly becomes an important limitation. Phosphodiesterase inhibitors represent an interesting option to increase contractility, also by increasing cyclic AMP levels in the myocardium. In this respect, the combination of phosphodiesterase inhibitors with adrenergic agents is attractive. The additional vasodilatory properties of these agents can contribute to the increase in cardiac output with limited risk of further reduction in arterial pressure. In 13 patients with cardiogenic shock persisting despite the use of adrenergic agents, the addition of enoximone, 0.5 mg/kg, resulted in significant increases in cardiac index and stroke volume index and a significant decrease in pulmonary artery balloon occlusion pressure without consistent change in mean arterial pressure. In 8 patients, a second infusion of 0.5 g/kg amplified these effects. All but one of these patients survived the episode of cardiogenic shock, and 5 patients were discharged alive. In some cases, even lower doses of enoximone resulted in dramatic increases in cardiac output and oxygen transport in patients already treated with dobutamine with limited success.
 ...
PMID:The role of enoximone in the treatment of cardiogenic shock. 217 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>