title: Synergic bronchodilator effects of a phosphodiesterase 3 inhibitor olprinone with a volatile anaesthetic sevoflurane in ovalbumin-sensitised guinea pigs.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesiology, Sapporo Medical University, Sapporo, Hokkaido, Japan. zhou.jing@sapmed.ac.jp
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Sohshi
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Watanabe
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamakage
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D020105:Milrinone / Q000494:pharmacology; D010047:Ovalbumin; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D000077149:Sevoflurane; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D001993:Bronchodilator Agents; D007093:Imidazoles; D008738:Methyl Ethers; D058987:Phosphodiesterase 3 Inhibitors; D011728:Pyridones; D000077149:Sevoflurane; C059498:olprinone; D010047:Ovalbumin; D013806:Theophylline; D020105:Milrinone; D000109:Acetylcholine