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Phosphodiesterase Inhibitor

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6641. Effects of the phosphodiesterase III inhibitors olprinone, milrinone, and amrinone on hepatosplanchnic oxygen metabolism. (Abstract)

Effects of the phosphodiesterase III inhibitors olprinone, milrinone, and amrinone on hepatosplanchnic oxygen metabolism. To measure the hepatic venous oxygen saturation in patients after cardiac surgery and to compare the effects of olprinone (OLP), a newly synthesized phosphodiesterase III inhibitor, with those of milrinone (MIL) and amrinone (AMR) on hepatosplanchnic oxygen dynamics. Phosphodiesterase III inhibitors are used to improve the hemodynamic state after cardiac surgery. However

2000 Critical care medicine Controlled trial quality: uncertain

6642. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. (Abstract)

vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown.Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment (...) Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure.Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated

2000 Journal of the American College of Cardiology Controlled trial quality: uncertain

6643. Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass. (Abstract)

Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass. Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta (...) -receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted

2001 Anesthesia and analgesia Controlled trial quality: uncertain

6644. Bioavailability of the oral selective phosphodiesterase 4 inhibitor cilomilast. (Abstract)

Bioavailability of the oral selective phosphodiesterase 4 inhibitor cilomilast. To determine the absolute bioavailability of cilomilast, and assess the effects of food, dosing time, and coadministration of antacid agents on its bioavailability and pharmacokinetics in healthy volunteers.Clinical pharmacology unit.Five prospective pharmacokinetic studies: one single-blind, dose-escalating, placebo-controlled trial; four open-label, randomized studies.Ninety-six healthy adult volunteers who were

2001 Pharmacotherapy Controlled trial quality: uncertain

6645. Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone. (Abstract)

Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone. In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given (...) 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10

1992 The Thoracic and cardiovascular surgeon Controlled trial quality: uncertain

6646. Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test. Full Text available with Trip Pro

Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test. 1. An approximately steady-state reduction of specific airway conductance was induced in normal human subjects by means of a methacholine individualized loading+maintenance dose regime. Tested against this background bronchoconstriction, the mixed type III/IV phosphodiesterase inhibitor AH 21-132, ingested in doses up to 90 mg, had

1992 British journal of clinical pharmacology Controlled trial quality: uncertain

6647. Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function. (Abstract)

Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function. Some phosphodiesterase (PDE)-inhibitors are believed to alter platelet count and function due to changes in intracellular cAMP. Whether newly developed (specific) PDE-inhibitors negatively influence platelet function in cardiac surgery should be investigated in a randomized study.Eighty patients undergoing aorto-coronary bypass grafting were divided into 4 groups and received (...) either the new PDE-III-inhibitor piroximone (group 1), the PDE-III-inhibitor enoximone (group 2), epinephrine (group 3) or no inotropic support (control). PDE-III-inhibitors were given as a bolus followed by infusion until starting of cardiopulmonary bypass (CPB). In addition to platelet count and a thrombelastogram, platelet function was assessed by aggregometry (ADP, epinephrine, collagen). Measurements were done before, during and after CPB until the 1st postoperative day.Platelet count

1992 Intensive Care Medicine Controlled trial quality: uncertain

6648. [Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients]. (Abstract)

[Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients]. The new phosphodiesterase-III inhibitor (PDI) enoximone is a non-catecholamine, non-glycoside cardiotonic agent with concomitant vasodilating properties. It has proved beneficial in patients with severe chronic heart failure. The influence of enoximone i.v. on hemodynamics was investigated during cardiac surgery under various conditions. METHODS. A randomized series of 60 patients undergoing

1989 Der Anaesthesist Controlled trial quality: uncertain

6649. A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. (Abstract)

A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. A multicenter randomized 4-week interindividual double-blind study was carried out in 58 hospitalized patients with major depressive disorder (DSM III 296.23, 296.22, 296.33, 296.32, 296.53 and 296.52) to test the dose-effect relationship of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram: 3 x 0.25 mg, 3 x 0.50 mg

1992 Neuropsychobiology Controlled trial quality: uncertain

6650. Haemodynamic effects of the phosphodiesterase inhibitor enoximone in comparison with dobutamine in esmolol-treated cardiac surgery patients. (Abstract)

Haemodynamic effects of the phosphodiesterase inhibitor enoximone in comparison with dobutamine in esmolol-treated cardiac surgery patients. 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

1990 British Journal of Anaesthesia Controlled trial quality: uncertain

6651. Acute pulmonary oedema: preliminary results of a randomized trial of the intravenous phosphodiesterase inhibitor, enoximone, vs conventional therapy. (Abstract)

Acute pulmonary oedema: preliminary results of a randomized trial of the intravenous phosphodiesterase inhibitor, enoximone, vs conventional therapy. The purpose of this open study was to compare the effects of enoximone and conventional therapy in 44 patients with acute pulmonary oedema. In this preliminary report, 22 patients were randomly assigned to the enoximone group (1 mg/kg bolus, every 8 hours for 48 hours) and 22 patients to conventional therapy (frusemide, nitrates, dopamine

1990 International journal of cardiology Controlled trial quality: uncertain

6652. Drug interactions: the new phosphodiesterase inhibitor enoximone and the calcium channel blocker nifedipine in coronary surgery patients--influence on hemodynamics and plasma concentrations. (Abstract)

Drug interactions: the new phosphodiesterase inhibitor enoximone and the calcium channel blocker nifedipine in coronary surgery patients--influence on hemodynamics and plasma concentrations. The calcium channel blocker nifedipine and the new phosphodiesterase (PDE) inhibitor enoximone are used in the treatment of cardiovascular diseases. Since both substances are acting on slow calcium channels and because systemic elimination of these two agents is dependent on oxidative drug metabolizing

1990 Journal of cardiovascular pharmacology Controlled trial quality: uncertain

6653. The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation. (Abstract)

The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation. 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

1990 Intensive Care Medicine Controlled trial quality: uncertain

6654. [Pharmacodynamic effects of the phosphodiesterase inhibitor enoximone during exposure to the volatile anesthetics halothane and isoflurane in coronary surgery patients]. (Abstract)

[Pharmacodynamic effects of the phosphodiesterase inhibitor enoximone during exposure to the volatile anesthetics halothane and isoflurane in coronary surgery patients]. We investigated the pharmacodynamic effects of the phosphodiesterae inhibitor enoximone in the presence of halothane and isoflurane in 20 patients, ASA class III, aged 45-75 years, undergoing coronary artery bypass grafting. The study was approved by the local Medical Ethics Committee and patients' informed written consent (...) increase in oxygen extraction. After bolus injection of enoximone oxygen extraction decreased significantly and returned to control value in group II. In group I enoximone decreased oxygen extraction significantly compared with control.Our results suggest that in the presence of halothane or isoflurane the phosphodiesterase inhibitor enoximone produces a comparable increase in cardiac output and decrease in systemic vascular resistance in patients with coronary artery disease.

1993 Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS Controlled trial quality: uncertain

6655. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. (Abstract)

Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. Zardaverine is a selective inhibitor of phosphodiesterase (PDE) III and IV isozymes. It has been shown to exert potent bronchodilator effects in animals. In order to study the efficacy and safety in man, a phase II clinical trial in 10 patients with partially reversible chronic airflow obstruction was carried out. The trial was designed as a double-blind

1995 Respiratory medicine Controlled trial quality: uncertain

6656. Effects of enoximone and R 80122, a new selective phosphodiesterase III inhibitor, on hemodynamics and myocardial energetics in patients with ischemic heart disease. (Abstract)

Effects of enoximone and R 80122, a new selective phosphodiesterase III inhibitor, on hemodynamics and myocardial energetics in patients with ischemic heart disease. The present study was designed to compare the effects of enoximone and R 80122, a highly selective phosphodiesterase (PDE) III inhibitor, on left ventricular hemodynamics and myocardial blood flow and metabolism in patients with coronary artery disease. Twenty male, anesthetized patients, ASA physical status III, were studied (...) , the PDE III inhibitor was infused over 2 min and measurements were repeated 5, 30, and 60 min after drug administration. There were no external stimuli to the patients during any of the measurement periods. R 80122 and enoximone decreased mean arterial pressure (MAP) by 20% and systemic vascular resistance (SVR) by 36% and 38%, respectively, while cardiac index (CI) increased by 27% and 30%, respectively. There were increases in heart rate (HR) by 10% and 19%, respectively, and in contractility (dp

1994 Anesthesia and analgesia Controlled trial quality: uncertain

6657. Differential effects of dobutamine and a phosphodiesterase inhibitor on early diastolic filling in patients with congestive heart failure. (Abstract)

Differential effects of dobutamine and a phosphodiesterase inhibitor on early diastolic filling in patients with congestive heart failure. This study was designed to compare the influence of beta-adrenergic stimulation (dobutamine) and a selective phosphodiesterase inhibitor (MS-857) on left ventricular diastolic performance and Doppler transmitral flow velocity patterns in patients with congestive heart failure and to elucidate the mechanisms for changes in early diastolic filling induced (...) by each agent.Both beta-adrenergic agonists and phosphodiesterase inhibitors act through the cyclic adenosine monophosphate pathway. However, it is controversial whether they have similar effects on diastolic performance. No previous studies have investigated the effects of these agents on Doppler-derived measurements of diastolic filling. We hypothesized that they would have different effects on early diastolic filling in patients with congestive heart failure.Twenty patients with chronic congestive

1995 Journal of the American College of Cardiology Controlled trial quality: uncertain

6658. Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting. (Abstract)

Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting. To investigate the hemodynamic effects and safety of R 80122, a novel selective phosphodiesterase (PDE) III inhibitor, and its solvent hydroxypropyl-beta-cyclodextrin.Prospective, randomized study.Operating theater of a university hospital in the Netherlands.Twelve patients with impaired left

1995 Journal of cardiothoracic and vascular anesthesia Controlled trial quality: uncertain

6659. [Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122]. (Abstract)

[Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122]. At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive peripheral vasodilatation (...) . As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim

1995 Der Anaesthesist Controlled trial quality: uncertain

6660. Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction. Full Text available with Trip Pro

Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction. Endothelial dysfunction is a key early event in the process of atherosclerosis and a risk factor for cardiovascular events. Sildenafil, an effective oral treatment for patients with erectile dysfunction, inhibits cGMP degradation by specific type 5 phosphodiesterase (PDE) inhibition. Sildenafil has been shown to improve vascular function, however, the effect of type 5 PDE inhibition (...) , improvement of 1.5%, P < .005).The present study shows, for the first time, that type 5 PDE inhibition with sildenafil abrogates the smoking-induced acute decrease in FMD of the brachial artery. These findings may have clinical implications given the detrimental consequences of smoking and the strategic role of normal endothelial function.

2004 American journal of hypertension Controlled trial quality: uncertain

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