Hirota K, Yoshioka H, Kabara S, Kudo T, Ishihara H, Matsuki A
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan.
Anesth Analg. 2001 Jul;93(1):230-3. doi: 10.1097/00000539-200107000-00046.
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.
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.
静脉注射氨茶碱，一种非选择性磷酸二酯酶（PDE）抑制剂，常用于治疗麻醉期间的哮喘发作。然而，在某些情况下，会观察到对氨茶碱耐药的发作。选择性PDE3抑制剂现已在临床上可用，并且据报道可产生支气管扩张作用。因此，我们比较了新型PDE3抑制剂奥普力农和氨茶碱对乙酰甲胆碱诱导的支气管收缩的舒张作用。用戊巴比妥麻醉犬。用乙酰甲胆碱（0.5微克/千克 + 5.0微克·千克⁻¹·分钟⁻¹）诱发支气管收缩，并通过支气管镜监测支气管横截面积（BCA；基础值 = 100%）的变化百分比来评估。最初，比较了奥普力农（n = 8；0 - 1000微克/千克）和氨茶碱（n = 8；0 - 50毫克/千克）的舒张作用。在开始输注乙酰甲胆碱前以及开始输注乙酰甲胆碱后30分钟和每次给予奥普力农或氨茶碱后5分钟评估支气管横截面积。然后我们确定普萘洛尔（0.4毫克/千克）是否能逆转奥普力农（1000微克/千克）和氨茶碱（50毫克/千克）诱导的舒张作用。奥普力农和氨茶碱剂量依赖性地拮抗支气管收缩，分别为56.2% ± 21.3%（标准差）和68.0% ± 30.3%，-log 50%有效剂量（平均值）分别为4.80 ± 0.38（15.8）微克/千克和1.96 ± 0.42（10.9）毫克/千克。50毫克/千克的氨茶碱显著增加血浆肾上腺素，而奥普力农则没有。此外，普萘洛尔显著降低氨茶碱诱导的舒张作用，但不降低奥普力农诱导的舒张作用。因此，奥普力农的舒张作用独立于血浆肾上腺素，而氨茶碱的作用可能部分是由于循环中肾上腺素浓度增加所致。
我们比较了奥普力农和氨茶碱对犬乙酰甲胆碱诱导的支气管收缩的舒张作用。奥普力农的舒张作用独立于血浆肾上腺素，而氨茶碱的作用可能部分由血浆肾上腺素增加引起。
