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Phosphodiesterase Inhibitor

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6001. Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test. (Full text)

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

6002. [Pharmacodynamic effects of the phosphodiesterase inhibitor enoximone during exposure to the volatile anesthetics halothane and isoflurane in coronary surgery patients]. (PubMed)

[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

6003. Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone. (PubMed)

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

6004. Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure. The Milrinone Multicenter Trials Investigators. (PubMed)

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure. The Milrinone Multicenter Trials Investigators. We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only (...) controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+26 +/- 8% vs. +5 +/- 7% in MIL-1077 and +11 +/- 5% vs. +2 +/- 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial

1993 Journal of the American College of Cardiology Controlled trial quality: uncertain

6005. [The anti-ischemic effect of phosphodiesterase III inhibitors]. (PubMed)

[The anti-ischemic effect of phosphodiesterase III inhibitors]. When enoximone is acutely administered to patients with stable angina and angiographically proven relevant coronary stenosis i.v. application of 0.75 mg/kg exhibits pronounced antiischemic effects. This could be observed in patients during exercise and in those in whom the ischemia was provoked by rapid cardiac stimulation. The antiischemic effects were documented by relief of symptoms, reduction of ST-depression, improvement

1994 Zeitschrift für Kardiologie Controlled trial quality: uncertain

6006. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. (PubMed)

Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Sildenafil (Viagra, UK-92,480) is a novel oral agent under development for the treatment of penile erectile dysfunction. Erection is dependent on nitric oxide and its second messenger, cyclic guanosine monophosphate (cGMP). However, the relative importance of phosphodiesterase (PDE) isozymes is not clear. We have identified both cGMP- and cyclic adenosine (...) monophosphate-specific phosphodiesterases (PDEs) in human corpora cavernosa in vitro. The main PDE activity in this tissue was due to PDE5, with PDE2 and 3 also identified. Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers, we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties (rapid absorption, relatively short half-life, no significant effect on heart rate and blood pressure) for an oral agent to be taken, as required

1996 International journal of impotence research Controlled trial quality: uncertain

6007. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. (PubMed)

Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. Increased cyclic AMP-phosphodiesterase activity in peripheral blood leukocytes is associated with the immune and inflammatory hyperreactivity that characterizes atopic dermatitis. Atopic phosphodiesterase has high sensitivity to a variety of enzyme inhibitors, suggesting an increased therapeutic advantage. The objective of this study was to use in vitro assays to identify a potent (...) phosphodiesterase inhibitor and then to investigate its effectiveness in treating atopic dermatitis. Leukocyte enzyme activity was measured by radioenzyme assay, whereas prostaglandin E2 and interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h culture supernatants of mononuclear leukocytes by immunoassays. The effect of a topical phosphodiesterase inhibitor on atopic dermatitis lesional skin was assessed by double-blind, paired comparisons of active drug and placebo ointments applied to symmetrically

1996 The Journal of investigative dermatology Controlled trial quality: uncertain

6008. 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. (PubMed)

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

6009. [Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122]. (PubMed)

[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

6010. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. (PubMed)

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

6011. Effects of enoximone and R 80122, a new selective phosphodiesterase III inhibitor, on hemodynamics and myocardial energetics in patients with ischemic heart disease. (PubMed)

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

6012. Differential effects of dobutamine and a phosphodiesterase inhibitor on early diastolic filling in patients with congestive heart failure. (PubMed)

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

6013. [Hemodynamic effects of amrinone, phosphodiesterase inhibitor, early after coronary artery bypass grafting]. (PubMed)

[Hemodynamic effects of amrinone, phosphodiesterase inhibitor, early after coronary artery bypass grafting]. This study was conducted to evaluate the hemodynamic effects of amrinone early after open-heart surgery. Eighteen patients who underwent coronary artery bypass grafting were randomly divided into two groups: ten patients (group A) were administered 5 micrograms/kg/min of amrinone, and eight patients (group B) were administered 10 micrograms/kg/min. No bolus of amrinone was administered

1996 [Zasshi] [Journal]. Nihon Kyōbu Geka Gakkai Controlled trial quality: uncertain

6014. Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. (PubMed)

Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during (...) their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index

1999 Japanese circulation journal Controlled trial quality: uncertain

6015. Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients. (PubMed)

Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients. The effect of topical administration of phosphodiesterase (PDE) 3 inhibitors on the airway is not clear. In order to examine the usefulness of inhaled PDE3 inhibitors in the treatment of asthma, we investigated the bronchodilator effect of inhaled olprinone, a newly developed PDE3 inhibitor, in nine asthmatic patients. On three separate study days, olprinone, salbutamol, or vehicle (...) was administered in a double-blind and randomized fashion, and pulmonary functions were assessed over 60 min. Significant increases in FEV(1) were observed until 45 min after inhalation of olprinone without adverse cardiovascular effects. Mean maximal increases in FEV(1) were 16.0 +/- 4.0 and 20.5 +/- 4.2% with olprinone and salbutamol, respectively. The bronchodilator effect of olprinone was greater than that of salbutamol in four of the nine patients. These results suggest that the inhaled PDE3 inhibitor has

1999 American journal of respiratory and critical care medicine Controlled trial quality: uncertain

6016. Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis. (PubMed)

Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis. Forty atopic dogs were studied for 28 days after the oral administration of four randomised treatments: (A) arofylline (1 mg/kg) twice daily for four weeks; (B) prednisone (0.5 mg/kg) twice daily for the first week, once a day during the second week and every 48 hours for the remaining two weeks; (C) prednisone following the same protocol but at a dose of 0.25 mg/kg

1999 The Veterinary record Controlled trial quality: uncertain

6017. Effects of the phosphodiesterase III inhibitors olprinone, milrinone, and amrinone on hepatosplanchnic oxygen metabolism. (PubMed)

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

6018. Modulation of tear film protein secretion with phosphodiesterase inhibitors. (PubMed)

Modulation of tear film protein secretion with phosphodiesterase inhibitors. A double-blind randomized clinical study was conducted to determine whether nicardipine hydrochloride was a useful treatment for dry eye.We examined its effect on the tear film, ocular surface and ocular comfort. Nicardipine hydrochloride, 3-isobutyl-1-methylxanthine and pilocarpine hydrochloride were dissolved in an artificial tear vehicle and applied topically to one eye of 12 subjects on separate days. Ocular

2000 Clinical & experimental ophthalmology Controlled trial quality: uncertain

6019. Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. (PubMed)

Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III (...) inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 +/- 44 and 60.6 +/- 8.0 ml/kg for the control and PDE III inhibitor groups. respectively). Four hours

2000 Heart and vessels Controlled trial quality: uncertain

6020. Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass. (PubMed)

Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass. Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients

2001 Acta Anaesthesiologica Scandinavica Controlled trial quality: uncertain

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