ovalbumin and olprinone

Phosphodiesterase 3 (PDE3) inhibitors and sevoflurane are both known to have bronchodilator properties and the combination of these two agents may be synergistic. We tested this hypothesis in a model of airway hyperresponsiveness using ovalbumin-sensitised guinea pigs.. Animals were randomised into five groups: control, sevoflurane, sevoflurane/theophylline, sevoflurane/milrinone and sevoflurane/olprinone. Total lung resistance (RL) and dynamic lung compliance (CL) were recorded and the dose-response curves for acetylcholine (Ach) of RL and CL were used to evaluate the bronchodilator effect.. The dose-response curve for Ach of RL was elevated that for and CL was depressed significantly in the ovalbumin-sensitised animals compared to normal control guinea pigs. Among the five sensitised groups, RL was higher in the order of control > sevoflurane > sevoflurane/theophylline > sevoflurane/milrinone > sevoflurane/olprinone with increasing Ach concentration. Sevoflurane/olprinone treatment attenuated the bronchoconstriction induced by the highest dose of Ach with RL being significantly lower (0.318 ± 0.056 cmH2O ml(-1) s(-1)) than those observed in the control group (0.437 ± 0.061 cmH2O ml(-1) s(-1)), sevoflurane group (0.378 ± 0.052 cmH2O ml(-1) s(-1)) and in the sevoflurane/theophylline group (0.374 ± 0.073 cmH2O ml(-1) s(-1)).. Combined use of PDE inhibitors with a volatile anaesthetic had a synergic bronchodilator effect in ovalbumin-sensitised guinea pigs. A greater bronchodilator effect can be obtained by using the selective PDE3 inhibitor olprinone with the volatile anaesthetic sevoflurane.

Topics: Acetylcholine; Airway Resistance; Anesthetics, Inhalation; Animals; Bronchial Hyperreactivity; Bronchoconstriction; Bronchodilator Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Guinea Pigs; Imidazoles; Lung Compliance; Male; Methyl Ethers; Milrinone; Ovalbumin; Phosphodiesterase 3 Inhibitors; Pyridones; Sevoflurane; Theophylline; Time Factors

Although phosphodiesterase (PDE) 3 and 4 inhibitors have received much attention for the treatment of bronchial asthma, systemic adverse effects have also been reported.. The purpose of this study was to investigate the effect of inhaled olprinone, a newly developed PDE3 inhibitor, and KF19514, a PDE1 and 4 inhibitor, on antigen-induced airway reactions in guinea-pigs.. Fifteen minutes after inhalation of olprinone (0.1 or 1.0 mg/mL) and KF19514 (0.1 or 0.01 mg/mL), animals were given an antigen challenge. Bronchial hyper-responsiveness and bronchoalveolar lavage fluid cell analysis were performed 24 h after the antigen challenge.. Inhalation of olprinone and KF19514 caused a dose-related inhibition of antigen-induced bronchoconstriction. Antigen inhalation significantly increased bronchoconstrictor responses to methacholine, and airway accumulation of neutrophils and eosinophils, 24 h after the antigen challenge. These responses were dose-dependently prevented by KF19514, but not by olprinone.. The results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Administration, Inhalation; Aerosols; Animals; Antigens; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Cyclic Nucleotide Phosphodiesterases, Type 1; Cyclic Nucleotide Phosphodiesterases, Type 3; Cyclic Nucleotide Phosphodiesterases, Type 4; Guinea Pigs; Imidazoles; Male; Methacholine Chloride; Naphthyridines; Ovalbumin; Phosphodiesterase Inhibitors; Pyridones