Synergic bronchodilator effects of a phosphodiesterase 3 inhibitor olprinone with a volatile anaesthetic sevoflurane in ovalbumin-sensitised guinea pigs

Abstract

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.