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)

In order to investigate the regulation of polyunsaturated fatty acid oxidation in the heart, the effect of the phosphodiesterase inhibitor enoximone on the oxidation of [1-14C] arachidonic acid, and [1-14C] arachidonyl-CoA, were studied in adult rat myocytes, and isolated rat heart mitochondria. Enoximone stimulated arachidonate oxidation by 94%, at a concentration of 0.25 mM. The apparent Vmax value of arachidonate oxidation in the presence of enoximone (6.98 nmol/mg protein/30 min), was approximately 75% higher than the value observed with the control (4.0 nmol/mg protein/30 min) in isolated myocytes. Also, enoximone stimulated arachidonate uptake by 27% at a concentration of 0.25 mM. On the other hand, enoximone had no effect on the oxidation of [1-14C] arachidonyl-CoA in isolated rat heart mitochondria. These results suggest that the oxidation of polyunsaturated fatty acids in myocytes is regulated by the rate of uptake of these acids across sarcolemmal membranes.
...
PMID:Stimulation of polyunsaturated fatty acid oxidation in myocytes by regulating its cellular uptake. On the rate limiting step of polyunsaturated fatty acid oxidation in heart. 182 96

For the past several years, the UTAH Cardiac Transplant Program has been investigating the use of enoximone, a phosphodiesterase inhibitor with unique properties, as an oral pharmacologic adjunct to conventional management of severe congestive heart failure in patients awaiting heart transplantation. The goal of this approach is not long-term survival, but the ability to maintain patients comfortably with adequate tissue perfusion until the donor heart becomes available. Enoximone exhibits both positive inotropic and vasodilator characteristics. It appears to be the only agent that produces positive inotropic effects by phosphodiesterase inhibition alone, and its effects appear to last significantly longer than those of beta-adrenergic agonists. The results of the program's clinical experience with 281 patients suggest that inotropic support with low-dose enoximone may be a useful adjunct in the short-term management of patients with severe end-stage congestive heart failure. Almost 25% of patients who had been dependent on intravenous inotropic support were able to be weaned from intravenous therapy and switched to oral enoximone. No acceleration in mortality while patients awaited transplantation was observed. The data also showed an increase in the beta 2-adrenergic receptors and a difference in the beta 1:beta 2-receptor subtype ratio of 56:42 with enoximone, compared with 65:35 in a group of failing control patients who received no enoximone. In addition, the combination of enoximone and beta-adrenergic agonists was not associated with beta-receptor down-regulation.
...
PMID:Enoximone as a bridge to heart transplantation: the Utah experience. 183 Feb 22

Enoximone is a phosphodiesterase inhibitor, which has been studied extensively for use in the management of patients with moderate-to-severe heart failure. The authors have studied the absorption and disposition kinetics of enoximone and its primary metabolite, enoximone sulfoxide, after both single oral doses of enoximone and at steady-state after short-term chronic oral therapy. A total of ten patients (two female, eight male) with moderate-to-severe heart failure (NYHA class II-IV) were enrolled into the study after giving written informed consent. The plasma levels of enoximone sulfoxide were greater than those of enoximone at all sampling times. The peak enoximone sulfoxide plasma concentrations ranged from 3.5 to 17.3 times the peak enoximone plasma levels for individual patients. The average steady-state plasma concentrations for enoximone were 115 +/- 40 ng/mL and 190 +/- 78 ng/mL for 50 mg every 8 hours and 100 mg every 8 hours dosage regimens, respectively. The absorption and disposition kinetics of enoximone were found to be significantly variable between patients. The authors also evaluated the relationship between dose administered and steady-state plasma levels as well as the relationship between the observed and predicted steady-state plasma levels. The authors found a linear relationship between the dose that was administered and the accrued plasma levels, as well as a good correlation between the predicted and observed steady-state levels. Although these data confirm previous reports that the sulfide metabolite of enoximone accumulates extensively in the plasma during oral therapy, reaching levels much higher than those of enoximone, these data do not support previous suggestions that the disposition of enoximone is nonlinear.
...
PMID:Disposition kinetics of orally administered enoximone in patients with moderate to severe heart failure. 183 16

Hemodynamic measurements were done in 42 patients with congestive heart failure of NYHA classes III and IV after administration of the phosphodiesterase inhibitors amrinone und enoximone. Amrinone decreases mean arterial pressure (-4%), right atrial pressure (-39%), and systemic vascular resistance (-23%), while cardiac index and stroke volume index increase to 27% and 26%, respectively; heart rate is nearly unchanged. Enoximone administration in a dose of 1 mg/kg bw produces an increase in cardiac index of 13%, an increase in heart rate of 12%, and a decrease of systemic vascular resistance of 13%, whereas stroke volume index is unchanged. Enoximone in a dose of 1.5 mg/kg bw increases heart rate (+ 9%), cardiac index (+ 33%), and stroke volume index (+ 21%), and decreases systemic vascular resistance (-26%). The hemodynamic profile of amrinone and enoximone in an equal dose shows only slight differences. Furthermore, phosphodiesterase inhibitors produce an increase of cardiac index (+ 19%) and stroke volume index (+ 17%) in patients with pump failure having already received dopamine and dobutamine.
...
PMID:[The hemodynamic profile of amrinone and enoximone in patients with severe heart failure]. 183

Enoximone, a new phosphodiesterase-inhibitor with positive inotropic and vasodilating activities is available for intravenous use in patients with severe heart failure. A review of the current knowledge regarding the adverse effects of this substance reveals that they are characterized by cardiovascular, central nervous, and gastrointestinal side effects. Adverse effects occurred in 20% of patients and were mostly due to the pharmacological properties of enoximone. Cardiovascular side effects (10%) were the most frequent; ventricular and supraventricular arrhythmias were most common. Two to three percent of the patients experienced hypotension due to the vasodilator activity of enoximone. Headache, insomnia, and anxiety were the most frequent adverse effects on the central nervous system. Three percent of the patients treated experienced vomiting, nausea, abdominal pain, and diarrhea. An increase of liver enzymes and serum glucose could be observed, mostly in patients with previous liver disease or diabetes. Pharmacokinetic drug interactions are not known; possible pharmacodynamic interactions result from the pharmacological properties of the drugs. Intravenous therapy with enoximone causes a few serious side effects that can only be controlled by careful observation of the patients treated.
...
PMID:[Tolerance of enoximone in patients with heart failure]. 183 4

In a randomized study, the haemodynamic effects of the new phosphodiesterase-III-inhibitor, enoximone, were compared with dobutamine in acutely beta-adrenoceptor blocked patients. Twenty patients scheduled for aorto-coronary bypass grafting suffering from tachycardia (heart rate (HR) greater than 100 beat min-1) were treated by infusion of esmolol, an ultra-short acting, selective beta 1-blocker. Twenty minutes after the start of esmolol, either enoximone 0.5 mg kg-1 as a bolus (n = 10) or dobutamine 5 micrograms kg-1 min-1 was administered. Haemodynamic effects were monitored for 40 min, including measurement of left ventricular haemodynamics. Esmolol reduced HR (-27%) and dP/dtmax (-38%) significantly in both groups. Cardiac index (CI) was decreased also. Enoximone increased Cl (+35%) and dP/dtmax (+39%) significantly, while no change in dobutamine-treated patients was observed. Systemic vascular resistance increased only in the dobutamine group (+44%).
...
PMID:Haemodynamic effects of the phosphodiesterase inhibitor enoximone in comparison with dobutamine in esmolol-treated cardiac surgery patients. 3286 2

The aim of these studies was to determine whether phosphodiesterase inhibition by enoximone is able to regulate differentially beta 1- and beta 2-adrenoceptor (AR)-mediated inotropic effects. Strips of human right atrial myocardium were stimulated with noradrenaline plus ICI 118,551 (selective beta 1-AR stimulation) or adrenaline plus CGP 20,712A (selective beta 2-AR stimulation). Concentration-effect curves were determined in the absence or presence of enoximone. Enoximone alone was shown to produce dose-related positive inotropic effects. In tissues from beta 1-blocker-treated patients, enoximone potentiated the responses to both beta 1-AR and beta 2-AR stimulation. There was a fall in -log EC50 (mol/l) of 0.7 +/- 0.2 (mean +/- SEM; n = 6) for beta 1-AR stimulation and of 0.6 +/- 0.1 (n = 10) for beta 2-AR stimulation. The potentiation of beta 2-AR responses in non-beta-blocker-treated patients was similar with a fall in -log EC50 (mol/l) of 0.5 +/- 0.1 (n = 6). The extent of potentiation was not significantly different between beta 1-AR and beta 2-AR stimulation, nor between beta 1-blocker-treated patients and non-beta-blocker-treated patients. Further experiments showed that the potentiation by enoximone of the effects of catecholamines was unaltered by diazoxide (n = 6). Enoximone thus causes positive inotropic effects and potentiates the effects of catecholamines acting through both beta 1- and beta 2-AR. These actions are consistent with inhibition of cyclic AMP hydrolysis. The potentiation of the effects of catecholamines by phosphodiesterase inhibition appears unaltered by prior patient therapy with beta 1 blockers.
...
PMID:Enoximone potentiates the positive inotropic effects of beta-1- and beta-2-adrenoceptor stimulation in human atrial myocardium. 197 34

Enoximone is a selective inhibitor of the phosphodiesterase-III enzyme (PDE-III) and possesses positive inotropic and vasodilatory properties. The PDE-inhibitor amrinone has been associated with adverse effects on coagulation by decreasing platelets. To investigate the influence of enoximone on hemostasis, 18 patients undergoing elective aorto-coronary bypass grafting and receiving enoximone were compared to a control group (n = 18). In addition, the plasma levels of enoximone and its major metabolite (enoximone-sulfoxide) were studied following a single injection (0.5 mg/kg) and during a continuous infusion (5 and 10 micrograms/kg.min) before, during and after extracorporeal circulation (ECC). No difference between study and control groups was found for the parameters of coagulation during the investigation period; in particular there were no differences in platelet count and platelet function (thrombelastography). Following the single bolus, peak plasma levels decreased during ECC to ineffective levels. Continuous infusion, however, maintained effective plasma levels of enoximone; sulfoxide levels were twice as high as enoximone concentrations up until the end of the investigation period. It is concluded that enoximone can be judged to be safe in respect to its effects on coagulation even following ECC and at relatively high doses. The use of continuous infusion results in plasma levels which remain at an effective concentration through to the time that the patient is transferred to the intensive care unit.
...
PMID:The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation. 213 82

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

In a prospective, randomized study the phosphodiesterase inhibitor enoximone was compared to dobutamine after open heart surgery. In either group 25 patients were treated with enoximone and dobutamine, respectively, beginning immediately after weaning from cardiopulmonary bypass until 4 hours postoperatively. The drug was administered as a continuous infusion of 5 micrograms/min/kg body weight. Under enoximone a significant increase of cardiac output [enoximone (E): + 100%; dobutamine (D): + 38%] and a significant decrease of pulmonary vascular resistance (E: -34%, D: +65%) and of total systemic vascular resistance (E: -59%, D: -7%) was achieved. Systemic blood pressure and heart rate were not different. Side effects were not observed. Enoximone proved to be safe and superior to dobutamine in low cardiac output states after open heart surgery.
...
PMID:The effect of enoximone and dobutamine on hemodynamic performance after open heart surgery. A clinical comparison. 214 72


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

---