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)

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.
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PMID:Pharmacodynamics of enoximone during intravenous infusion. 214 32

Ten patients with severe heart failure, symptomatic despite treatment with diuretics and captopril, completed a study of the effect of adding enoximone to their normal treatment. Enoximone or matching placebo was given for 4 weeks in randomized double-blind order following a single-blind placebo run-in period. Exercise capability was measured with two different treadmill protocols, a corridor walk test and by step-counting with body-worn pedometers. Cardiac output and limb blood flow were assessed non-invasively by measuring respiratory gases and by venous occlusion plethysmography. Measurements were made at rest and in response to treadmill exercise. The mean exercise tolerance measured using the modified Bruce treadmill protocol was increased from the placebo value (498 +/- 91 seconds) after both 2 weeks (573 +/- 94 seconds, P = 0.051) and 4 weeks of enoximone (572 +/- 100 seconds, P = 0.057). Enoximone increased exercise duration in fixed workload tests from the placebo value (252 +/- 75 seconds) after 2 weeks' treatment (431 +/- 98 seconds, P = 0.011) and after 4 weeks (381 +/- 85 seconds, (P = 0.01). The percentage improvement with the fixed workload test was greater than with the modified Bruce protocol at week 2 (P = 0.03) and at week 4 (P = 0.051). Enoximone increased the speed of walking 100 m at self-selected slow, normal and fast paces. It had little effect on customary activity of the patients. Enoximone increased cardiac output measured at rest and during submaximal exercise (P = 0.001). It also improved blood flow to the calf muscle at rest and after exercise (P = 0.01). Enoximone has a beneficial effect in chronic heart failure symptomatic despite treatment with diuretics and captopril. The magnitude of its effect, however, depends upon the technique used to assess it.
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PMID:Effects of enoximone in patients with heart failure uncontrolled by captopril and diuretics. 214 38

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.
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PMID:Addition of phosphodiesterase inhibitors to adrenergic agents in acutely ill patients. 214 39

Cardiac transplantation is theoretically the optimal final treatment of terminal cardiac failure but the indications, especially in the emergency situation, should be carefully considered. Sympathomimetic agents are of limited use in patients with severe cardiac failure partly because of the down regulation of the myocardial beta-receptors. The phosphodiesterase inhibitors, represented by enoximone, are valuable because of their action on the cardiac muscle (inotropic and lusitropic) and their direct systemic vasodilator effect. Enoximone can be administered by intravenous bolus resulting in a rapid onset of action (peak at 30 minutes) with a prolonged effect due to its hepatic metabolites. The authors' experience in this indication dates over 5 years and over 50 patients were included. A preliminary study in 34 patients with cardiac failure resistant to betamimetic drugs, referred to the intensive care unit for urgent cardiac transplantation, or, in the absence of a donor, circulatory assistance is reported. A Swan Ganz catheter and radial artery canula were inserted for haemodynamic monitoring and enoximone was administered in an intravenous bolus over 15 minutes every 8 hours in addition to sympathomimetic agents. A haemodynamic improvement was observed after the 30th minute in 30 patients. The cardiac index increased from 1.82 to 2.67 l/mn/m2 and the pulmonary capillary pressures decreased from 30.8 to 18.9 mmHg. Systemic arterial resistances fell from 2,170 to 1,520 dynes.s.cm-5. No haemodynamic improvement was observed in 4 patients who were treated by mechanical ventricular assistance. After investigations to detect contra-indications to cardiac transplantation, 12 of the 30 patients remained candidates for cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Medical strategy in patients awaiting emergency heart transplantation]. 214 25

The effects of Enoximone (50 mg in 20 minutes) on systemic, pulmonary and coronary haemodynamics and on regional systolic function were examined after surgical myocardial revascularisation in 5 patients without overt cardiac failure. The flow in mammary artery grafts and the study of regional systolic function were assessed by Doppler probes implanted during the operation. Enoximone increased Qc and Qco without changing blood pressure or cardiac output, due to arterial vasodilatation and inotropic stimulation. Pulmonary vasodilatation resulted in hypoxemia which must be prevented. The increase in VO2 was unrelated to oxygen transport suggesting a specific drug related effect.
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PMID:[Postoperative enoximone in coronary surgery. Systemic and coronary hemodynamics and regional systolic function]. 214 29

Enoximone, a phosphodiesterase inhibitor, is a positive inotropic agent with direct vasodilator properties. Its acute effects after I.V. administration and the possibility of oral relay were studied in 14 patients (13 men and 1 woman), 40 to 78 years of age (mean 61 years) with Stage IV cardiac failure (NYHA Classification). Eleven patients had dilated cardiomyopathy, 2 had ischemic heart disease and 1 a dilated hypertrophic cardiomyopathy. The haemodynamic inclusion criteria were: cardiac index less than or equal to 2.2 l/mn/m2 and pulmonary capillary pressure greater than or equal to 18 mmHg. Patients with cardiogenic shock and severe renal or hepatic failure were excluded. The drug was administered as a bolus of 1 mg/kg followed by a continuous infusion of 5 to 15 g/kg/mn (average 8.9 +/- 2.6 for 7 to 72 hours; average 27 +/- 16 hours). Haemodynamic effects of I.V. administration: no change in heart rate, slight lowering of blood pressure, very significant reduction in right atrial and pulmonary capillary pressures, of pulmonary artery pressures, of arteriolo-capillary and systemic resistances and marked increase in cardiac output. General tolerance was excellent with no clinical secondary effects and no signs of hepatic, renal or haematological (platelets) toxicity. Cardiac tolerance was also excellent, no aggravation of preexisting arrhythmias. There was no immediate mortality. Oral relay was undertaken in 14 patients with a daily dose of 300 mg in 12 cases, 400 mg in 1 case and 500 mg in 1 case. Six patients underwent control haemodynamic evaluation on the 8th day: there were no signs of the haemodynamic improvement obtained by I.V. administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Enoximone: hemodynamic effect in patients with cardiac insufficiency]. 214 30

The aim of this study was to evaluate the efficacy and pharmacokinetics of enoximone administered as an intravenous bolus in 12 patients (mean age 62 years) with severe chronic congestive cardiac failure (Stage IV of the NYHA) due to ischemic (N = 6) or idiopathic (N = 6) cardiomyopathy. The haemodynamic parameters and plasma concentrations of enoximone and its metabolite were measured 15, 30, 60, 90, 120 minutes, 4 and 6 hours, after IV bolus of enoximone 1 mg/kg in 10 minutes. Enoximone increased the cardiac index by an average of 37 p. 100 (1.92 +/- 0.3 to 2.63 +/- 0.35 l/mn/m2; p less than 0.001); pulmonary artery diastolic pressures fell by 33 p. 100 (p less than 0.01). Systemic arterial resistances decreased by 23 p. 100 (p less than 0.05). No significant changes in heart rate or blood pressure were observed. The peak effect was recorded between the 15th and 30th minute. The pharmacokinetic study showed the half life of enoximone to be 2.2 +/- 0.78 hours, the area under the curve to be 2,818 +/- 953, the volume of distribution to be 69.6 +/- 24 l and the total clearance to be 22.8 +/- 8.5 l/hour. The half life of the metabolite was 4.45 +/- 1.05 hours. There was a significant correlation between the percentage increase in cardiac index and peak enoximone concentration (r = 0.91; p less than 0.001). In conclusion, an IV bolus of enoximone is an effective treatment for chronic cardiac failure. The haemodynamic response was related to the peak enoximone plasma concentration.
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PMID:[Treatment of chronic cardiac insufficiency with intravenous bolus enoximone. Study of a pharmacokinetic-hemodynamic relation]. 214 39

The authors discuss the physiopathological mechanisms of intra and postoperative cardiac failure and the different means of treatment. A distinction is made between the intra and postoperative periods: the factors which predispose to cardiac failure are different and the immediate postoperative period would seem to be the most dangerous in patients with reduced coronary or contractile reserves. Enoximone is a valuable and effective inotropic agent in this situation.
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PMID:[Postoperative cardiac insufficiency. The value of enoximone]. 214 41

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


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