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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In severe chronic congestive cardiac failure the physician has the choice of two families of positive inotropic agents, the direct sympathomimetics and the phosphodiesterase inhibitors. The aim of the study was to compare the efficacy and tolerance of enoximone and dobutamine in this indication. Twenty patients with severe chronic cardiac failure with a cardiac index of less than 2.2 l/min/m2 and pulmonary capillary pressure of over 20 mmHg were randomised into two groups in an open trial. One group received enoximone 50 micrograms/kg/min for 30 minutes then 10 micrograms/kg/min and the other received dobutamine 10 micrograms/kg/min. The two groups were comparable. Results were analysed 12 hours after starting therapy, well after the loading dose of enoximone and before the appearance of tolerance to dobutamine. Neither drug caused a significant change in heart rate or mean blood pressure. The pressure-rate product did not increase significantly with enoximone (+9.2% NS) in contrast with the dobutamine group in which a significant elevation was observed (+23.5%, p less than 0.05). The cardiac index increased with enoximone (+61.0%, p less than 0.01) and with dobutamine (+32.1%, p less than 0.02). This resulted mainly from an increase in the systolic index (+45.5%, p less than 0.05 with enoximone and +30.1%, p less than 0.05 with dobutamine). Pulmonary capillary pressure and total systemic resistance decreased with enoximone (-29.1%, p less than 0.001 and -36.7%, p less than 0.05 respectively) and with dobutamine (-23.4%, p less than 0.001 and -20.7%, p less than 0.05 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Enoximone/dobutamine comparison in chronic congestive cardiac insufficiency with low cardiac output]. 214 31

Theoretically, there are two reasons for using the association of dobutamine and enoximone in patients with acute cardiac failure; the powerful vasodilator effect of enoximone and the different biochemical actions of the two drugs on the myocardial fibre affecting the production (dobutamine) or the degradation (enoximone) of cyclic AMP. The combined effects of beta adrenergic agonists and phosphodiesterase III inhibitors in vitro and in vivo have been previously reported. An increased contractile response to dobutamine has been demonstrated with enoximone on isolated human ventricle obtained during cardiac transplantation. We confirmed the additive effect of dobutamine (5 to 10 micrograms/kg/min) and enoximone (1 mg/kg/bolus IV) in 8 patients with acute cardiac failure with each molecule used alone. Mild changes in heart rate (+19 bpm) and in systolic blood pressure (-3 mmHg) were observed simultaneously. The absence of an increase in SvO2 compared to the use of each molecule in monotherapy is probably related to a tendency to increase myocardial oxygen consumption which may be potentially deleterious in terms of gas exchange. Having demonstrated the additive effects of the association of dobutamine and enoximone, there is probably a place for this therapeutic association in the management of acute cardiac failure. However, the potential risk of inducing an atrial and/or ventricular tachyarrhythmia and the consequences of lowering ventricular filling pressures and systemic vascular resistances should be born in mind; when using this therapeutic association, the authors suggest starting treatment with low doses of dobutamine (5/kg/min) and enoximone (0.5 - 1 mg/kg) with haemodynamic control and steadily increasing the doses, depending on the results obtained.
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PMID:[Role of the enoximone-dobutamine combination in the treatment of congestive cardiac insufficiency]. 214 32

A 58-year-old male patient with end-stage cardiomyopathy suffered from cardiac decompensation under parenteral catecholamine medication. Oral therapy with 450 mg Enoximone daily achieved recovery after 4 weeks, so that an orthotopic cardiac transplantation could be performed. The postoperative outcome was uneventful. Selective phosphodiesterase-inhibitors help to fill a therapeutic gap in the management of catecholamine-refractory heart failure.
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PMID:[Oral enoximone therapy as a therapeutic bridging before heart transplantation]. 214 96

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.
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PMID:Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine. 215 89

Intracellular Ca2+ release and reuptake are necessary for normal contraction and relaxation of the human heart. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited two distinct components. Muscles from the failing hearts showed a diminished capacity to restore a low resting Ca2+ level during diastole. These data obtained in actively contracting human myocardium suggest that intracellular Ca2+ handling is abnormal and might cause both systolic and diastolic dysfunction in heart failure. The inotropic effectiveness of drugs that act to increase intracellular levels of cyclic adenosine monophosphate (AMP), such as beta-adrenergic agonists and phosphodiesterase inhibitors, was markedly reduced in muscles from patients with heart failure. In contrast, the effectiveness of inotropic stimulation with drugs that act by cyclic AMP-independent mechanisms, such as the cardiotonic steroids and DPI 201-106, were preserved. Stimulation of intracellular cyclic AMP production by the adenylate cyclase activator forskolin restored the inotropic response to phosphodiesterase inhibitors. These studies indicate that an abnormality in cyclic AMP production may be a fundamental defect in patients with end-stage heart failure that may markedly diminish the effectiveness of agents that depend on generation of this nucleotide for a positive inotropic effect. Moreover, deficient production of cyclic AMP seems, at least in part, to account for the reversal of the force-frequency relation that characterizes failing myocardium. Of interest, direct measurement of total cellular cyclic AMP content and protein kinase activity did not reveal significant differences between the control and myopathic tissue, suggesting the presence in human ventricular muscle of physiologically distinct compartmentalized pools of cyclic AMP. Finally, changes in the sensitivity of the contractile apparatus to Ca2+ also seem to play an important role in the differential responsiveness to drugs of myopathic versus normal human myocardium.
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PMID:Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. 215 79

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.
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PMID:The role of enoximone in the treatment of cardiogenic shock. 217 30

Milrinone is a phosphodiesterase inhibitor which combines vasodilating effects with inotropic effects. Hemodynamic improvement after acute administration and increased survival with chronic milrinone therapy in rats with heart failure have been reported before, and suggest long-term hemodynamic improvement. However, no detailed hemodynamic studies are available on prolonged milrinone therapy in rats with heart failure. Therefore, the hemodynamic effects of 2 weeks' milrinone therapy were now investigated in conscious rats with heart failure due to myocardial infarction. The effects were compared to hemodynamic changes after acute administration. Acute milrinone increased the baseline cardiac output in infarcted rats by increasing heart rate rather than stroke volume. However, the maximal cardiac output achieved when the heart was stimulated through a volume load was improved due to increased stroke volume as well as increased heart rate. The increase in maximally stimulated cardiac output after acute milrinone was found to be related to infarct size. Two weeks' milrinone therapy in chronically infarcted rats dose dependently restored the hemodynamic changes which were caused by infarction. In contrast to acute administration, two weeks' milrinone restored cardiac function without an increase in heart rate. The effects were achieved at a rate of administration which presumably has no acute inotropic effects. The data indicate that acute milrinone in infarcted rats has vasodilating effects. Positive inotropic effects, possibly masked by concomitant venodilatation at baseline conditions, became overt after stimulation by volume loading. Long-term milrinone dose dependently restored cardiac function in infarcted rats without effects on heart rate or mean arterial pressure, suggesting that different mechanisms may be involved.
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PMID:Beneficial hemodynamic effects of two weeks' milrinone treatment in conscious rats with heart failure. 222 21

The pharmacologic treatment of heart failure and low cardiac output syndrome in the cardiac surgical patient continues to be a challenge in the nursing management of these patients. While the catecholamines have been of proven inotropic benefit over the years, their inherit risks of increased myocardial oxygen consumption, tachyphylaxis and poor tolerance in many patients have lead to the search for other medications to augment cardiac performance. Amrinone, the only drug available for use in the U.S. from the class of phosphodiesterase inhibitors, acts as both an inotrope and vasodilator to increase cardiac output without an increase in myocardial oxygen consumption. This paper reviews pharmacological management of heart failure in the cardiac surgical patient and nursing considerations specific to amrinone and combination inotropic therapy management.
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PMID:Management of heart failure in cardiac surgical patients: amrinone and other pharmacologic agents. 226 43

Before it reaches the decompensation stage, heart failure is characterized by symptoms which occur only during exercise. It is therefore rational to believe that the effectiveness of treatments of heart failure should be evaluated by the improvement they produce in tolerance to stress. This tolerance can be evaluated by exercise tests which may take different forms. The most common is a progressive load test on bicycle ergometer or treadmill. Among the indices used to assess tolerance to stress, the total duration of the exercise test until symptoms develop is a variable subject to fluctuations which may be independent of the patient's cardiovascular state. Measurement of oxygen consumption at peak exercise level is usually preferred, being unrelated to the nature of the stress and much more reproducible and sensitive to changes. Among the pharmacological treatments of heart failure, only chronic vasodilator therapy, notably with angiotensin-converting enzyme inhibitors, has proved constantly effective on the various ergometric indices. In the literature, the effects of digitalis compounds, dihydralazine and alpha-blockers are inconstant. Among the new treatments of heart failure, phosphodiesterase inhibitors may improve tolerance to stress, as does Corwin which may prolong the total duration of exercise. Its effect on oxygen consumption has not yet been evaluated. Performance at exercise is almost never improved by acute treatment with any pharmacological agent, and the same remarks applies to short-term heart transplantation. The reason for this is that heart failure is associated with a physical deconditioning syndrome due to abnormalities of the arterial dilatation capacity in skeletal muscles, and with muscular metabolic abnormalities due to a defective oxygen utilization by these muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Usefulness of exercise tests in the evaluation of the effects of treatment in chronic cardiac insufficiency]. 226 63

Cyclic nucleotide phosphodiesterase (PDE) isozymes isolated by DEAE-Sephacel or Mono-Q High Performance Liquid Chromatography from cardiac left ventricular tissue of normal subjects and patients with end-stage heart failure have been compared. With both separation techniques, four major peaks of PDE activity were evident in the soluble fractions; only one peak of activity was present in particulate fractions. The specific activity of the particulate PDE from myopathics was approximately 30-50% of that of normals while the specific activity of a soluble form of this PDE (peak IIIa) was reduced by 30% in myopathics. No differences in comparison of the other peaks of PDE activity were evident. The particulate PDE isozyme has a low Km for cAMP (0.27-0.29 microM), is inhibited by cGMP (60-80% at 1 microM), is sensitive to inhibition by submicromolar concentrations of CI-930 but not rolipram, and is competitively inhibited by milrinone (Kj = 0.3 microM). The first soluble peak of PDE activity hydrolyzes both cAMP and cGMP and is stimulated by calmodulin while cyclic AMP hydrolysis by peak II PDE is stimulated by cGMP. The other soluble peak III fractions (IIIa and IIIb) hydrolyze cAMP; peak IIIa is inhibited by cGMP or by CI-930 and milrinone, whereas peak IIIb is also inhibited by rolipram when the cardiotonic sensitive PDE is inhibited by CI-930. Thus, cardiotonic-sensitive, cGMP-inhibitable, low Km cAMP PDE is present in both the soluble and particulate fractions of human cardiac left ventricular muscle of hearts from normal and cardiomyopathic subjects while the rolipram-sensitive PDE is present in the soluble fraction. The major differences in PDE activity of myopathic relative to normal left ventricular tissue are a reduced specific activity and Vmax of particulate PDE and one of the soluble peak III PDEs.
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PMID:Cellular distribution and pharmacological sensitivity of low Km cyclic nucleotide phosphodiesterase isozymes in human cardiac muscle from normal and cardiomyopathic subjects. 228 32


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