A comparison of the relaxant effects of olprinone and aminophylline on methacholine-induced bronchoconstriction in dogs.
IV aminophylline, a nonselective phosphodiesterase (PDE) inhibitor, is often used to treat an asthma attack during anesthesia. However, in some instances, aminophylline-resistant attacks are observed. Selective PDE3 inhibitors are now clinically available and have been reported to produce bronchodilation. Thus, we compared the relaxant effects of olprinone, a novel PDE3 inhibitor, and aminophylline on methacholine-induced bronchoconstriction. Dogs were anesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg/kg + 5.0 microg. kg(-1). min(-1)) and assessed as percentage of changes in the bronchial cross-sectional area (BCA; basal = 100%) monitored by bronchoscope. Initially, the relaxant effects of olprinone (n = 8; 0-1000 microg/kg) and aminophylline (n = 8; 0-50 mg/kg) were compared. The bronchial cross-sectional areas were assessed before and 30 min after methacholine infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg) and aminophylline (50 mg/kg). Olprinone and aminophylline dose-dependently antagonized bronchoconstriction by 56.2% +/- 21.3% (SD) and 68.0% +/- 30.3% with -log 50% effective dose (mean) of 4.80 +/- 0.38 (15.8) microg/kg and 1.96 +/- 0.42 (10.9) mg/kg, respectively. Aminophylline 50 mg/kg significantly increased plasma epinephrine, whereas olprinone did not. In addition, propranolol significantly reduced aminophylline-induced relaxation, but not olprinone-induced relaxation. Therefore, the relaxant effects of olprinone are independent of plasma epinephrine, whereas aminophylline effects may partially result from increased circulating concentrations of epinephrine.


CONCLUSIONS
We compared the relaxant effects of olprinone and aminophylline on methacholine-induced bronchoconstriction in dogs. The relaxant effects of olprinone are independent of plasma epinephrine, whereas the aminophylline effects may be partly caused by an increase in plasma epinephrine.
Hirota
K
K
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan. masuika@cc.hirosaki-u.ac.jp
Yoshioka
H
H
Kabara
S
S
Kudo
T
T
Ishihara
H
H
Matsuki
A
A
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001980:Bronchi / Q000033:anatomy & histology / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D002395:Catecholamines; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D016210:Methacholine Chloride; D000628:Aminophylline; C059498:olprinone