Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
...
PMID:[Medical strategy in patients awaiting emergency heart transplantation]. 214 25

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)
...
PMID:[Enoximone: hemodynamic effect in patients with cardiac insufficiency]. 214 30

Forty patients developed low cardiac output states after surgery for mitral valve disease or with associated cardiac disease and were randomly allocated to two treatment groups, one group to receive Dobutamine (D) and the other Enoximone (E), a phosphodiesterase inhibitor. Haemodynamic assessment covered a 24 hour period but treatment was continued for as long as was necessary. An improvement was observed from the 15th minute of treatment. At the second hour, the cardiac index had increased by 55% in Group E and by 59% in Group D whilst the heart rate increased by only 12% in Group E compared to 30% in Group D. The right and left heart filling pressures decreased by 25 to 27% in the 2 groups. The systemic arterial resistances fell by 36 to 37% without any significant changes in systemic or pulmonary arterial pressures. No significant difference was demonstrated in the haemodynamic responses to Dobutamine and Enoximone in this study. The duration of treatment was significantly shorter in Group E than in Group D (59 +/- 22 hrs vs 86 +/- 49 hrs) as was the patient's stay in the intensive care unit (92 +/- 37 hrs vs 155 +/- 129 hrs). The duration of assisted ventilation was the same in the two groups. These results suggest that Enoximone is as effective as Dobutamine in the treatment of low cardiac output after mitral valve surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Comparison of the hemodynamic effects of dobutamine and enoximone in the treatment of low cardiac output after valvular surgery]. 214 36

Enoximone is a new cardiotonic agent, active by both intravenous and oral routes of administration. Its pharmacological effects are due to the inhibition of the type IV phosphodiesterase: positive inotropism, vasodilatation and positive chronotropic action. The efficacy of enoximone in improving cardiovascular function in patients with congestive heart failure has been documented in many studies, but not in studies having mortality as the main end-point. In conclusion, enoximone cannot be safely proposed yet for the chronic treatment of congestive heart failure in association with classic management, until convincing evidence of its long-term benefit/risk profile will be given.
...
PMID:[Enoximone]. 214 96

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.
...
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.
...
PMID:Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine. 215 89

Enoximone is a selective inhibitor of a low Km, cyclic AMP-specific type of phosphodiesterase (PDE III). In guinea pig and chicken atria, enoximone (0.1-100 mumol/L) caused a weak increase in the force of contraction. The heart rate was slightly enhanced or was unchanged (chicken). Enoximone (30 mumol/L) also failed to shift the concentration-response curves for the positive inotropic and chronotropic effects of norepinephrine in guinea pig atria. Under almost the same conditions, enoximone and the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated the forskolin-induced mobilization of choline from phospholipids. The concentrations of IBMX (100 mumol/L) and of enoximone (50 mumol/L) used were equieffective and did not enhance choline mobilization by themselves. Cardioinhibition caused by acetylcholine was unaffected by enoximone. In perfused guinea pig hearts, the release of [3H]norepinephrine evoked by field stimulation (5 Hz) was increased by 50 mumol/L enoximone both in the absence and presence of cocaine plus corticosterone. In contrast, enoximone failed to alter the release of acetylcholine in chicken hearts at rest and during field stimulation (5 Hz), which directly depolarizes the intrinsic post-ganglionic nerves. Similar results were obtained in guinea pig hearts using [3H]acetylcholine. In contrast, when the release of labeled or unlabeled acetylcholine was evoked by (preganglionic) vagal stimulation, enoximone (30 and 50 mumol/L) and IBMX (50 mumol/L) reduced the release in both species. Taken together, enoximone and IBMX apparently reduced ganglionic transmission. The results further indicate functional compartmentalization of PDE III in guinea pig myocardial cells. PDE III appears to be involved in the regulation of myocardial choline-phospholipid hydrolysis and of norepinephrine release.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of the phosphodiesterase inhibitor enoximone on the autonomic innervation of the isolated heart. 248 Apr 84

Enoximone belongs to a new class of inotropic drugs that are not related either to digitalis or to catecholamines. It acts primarily through selective inhibition of phosphodiesterase III (PDE-III) and has additional vasodilating properties. Hemodynamic effects of intravenously administered enoximone (0.5 mg/kg) were investigated in patients undergoing aortocoronary bypass grafting before and during anesthesia as well as during extracorporeal circulation (ECC). Patients who were impossible to be weaned off ECC without pharmacological support were investigated also. A significant increase in cardiac index and dp/dtmax, a decrease in pulmonary capillary pressure, and a small decrease in mean arterial pressure were the major hemodynamic effects. Heart rate was not changed and no signs of arrhythmia were seen during the entire investigation period. Interactions with the anesthetics used could not be observed in this study. In patients with impaired myocardial performance during weaning from ECC, enoximone seems to be helpful in stabilizing cardiac output and decreasing filling pressure. The mechanism for improvement appears to be enhanced contractility due to its positive inotropic effects, as well as a decrease in left ventricular outflow resistance resulting from peripheral vasodilation.
...
PMID:Hemodynamic effects of enoximone in cardiac surgery patients. 248 Apr 86

The existing management of severe chronic congestive heart failure carries a dismal prognosis. Mortality over 6 months is 50% by some estimates. This fact, coupled with increasing concern for the safety and efficacy of the digitalis glycosides, has stimulated an intense search for new oral cardiotonic agents suitable for chronic administration. Despite the ability of many phosphodiesterase inhibiting agents to affect profound hemodynamic improvements acutely after oral or intravenous administration, none of the four agents here reviewed in 30 clinical trials has been adequately proven to provide benefit over conventional long-term therapy of severe heart failure. The four drugs to have undergone long-term clinical trials are amrinone, milrinone, enoximone (MDL 17043), and piroximone (MDL 19,025). For amrinone, inefficacy was revealed through carefully designed, placebo-controlled studies despite initial enthusiasm generated by open uncontrolled trials. Enoximone has suffered rapid attenuation of its hemodynamic effectiveness in most studies, and piroximone failed in its only long-term trial. Therefore, final judgment on most of these agents must await completion of controlled clinical trials, and any initial optimism stimulated by the current uncontrolled studies should be met with reservation.
...
PMID:Long-term oral therapy of congestive heart failure with phosphodiesterase inhibitors. 252 82

Twenty patients with moderately severe congestive heart failure were randomized to chronic enoximone (n = 10) or placebo (n = 10) therapy in a double-blind manner and serially evaluated over a 16-week-period. The purpose of the study was to determine if the addition of standard doses (1 and 2 mg/kg) of this new phosphodiesterase inhibitor to conventional therapy (digitalis and diuretics) would alter the clinical and laboratory course of this patient population. Except for a transient improvement in the quality of life score, none of the symptomatology indicators were significantly affected by enoximone. Similarly, maximal exercise capacity was not altered. Enoximone did elicit a statistically significant augmentation of echocardiographic, radionuclide angiographic, and systolic time interval parameters of left ventricular function. These enoximone-induced effects were accompanied by a significant increase (7% to 11%) in resting heart rate. Enoximone is capable of improving ventricular function when added to digitalis-diuretic therapy in moderately severe congestive heart failure. While individual patients may benefit from enoximone, the ability of standard doses of this agent to improve symptoms and exercise capacity over a 16-week period appears somewhat limited in a moderately severe heart failure population as a whole. Furthermore, a disparity between improvement in ventricular function parameters and changes in clinical status and exercise performance is apparent in this heart failure population.
...
PMID:Disparity between improvement in left ventricular function and changes in clinical status and exercise capacity during chronic enoximone therapy. 252 34


<< Previous 1 2 3 4 5 6 7 Next >>

---