Dagg K D, Clayton R A, Thomson L J, Chalmers G W, McGrath J C, Thomson N C
Department of Respiratory Medicine, North Glasgow Hospitals University NHS Trust, Glasgow, G12 0YN, UK.
Pulm Pharmacol Ther. 2001;14(2):99-105. doi: 10.1006/pupt.2000.0275.
These studies examine the effect of acute hypoxia on airway smooth muscle relaxation in response to salbutamol in vitro in human isolated bronchi from non-asthmatics and in vivo in-patients with asthma. Isometric responses were measured from rings of human bronchi pre-constricted with methacholine under oxygen tensions of 95% (hyperoxia), 20% (normoxia) and 4% (hypoxia). Once contractions had plateaued, concentration - response curves were conducted to salbutamol (10(-9)-10(-4)m). Twelve stable asthmatic patients were studied in a randomised double blind fashion. On two study days following baseline measurements, patients were randomised to receive either oxygen (FiO(2)1.0) or a hypoxic gas mixture (FiO(2)0.15) followed by three incremental doses of nebulised salbutamol at 15 min intervals. On two further study days nebulised saline was administered instead of salbutamol. In isolated bronchi, salbutamol-induced relaxations were significantly (P< 0.001) greater in hyperoxia and normoxia (P< 0.01) when compared to hypoxia. Among patients with asthma no significant differences were found in the mean maximum % change in forced expiratory volume (FEV(1)) from baseline between the hypoxic and hyperoxic study days on which nebulised salbutamol was administered. We conclude that acute hypoxia attenuates airway smooth muscle relaxation in response to salbutamol in vitro but has no effect on salbutamol-induced bronchodilation in in-patients with asthma.
这些研究在体外对来自非哮喘患者的人离体支气管以及体内对哮喘患者，检测了急性低氧对沙丁胺醇诱导的气道平滑肌舒张的影响。在95%（高氧）、20%（常氧）和4%（低氧）的氧分压下，测量用乙酰甲胆碱预收缩的人支气管环的等长反应。一旦收缩达到平台期，就对沙丁胺醇（10⁻⁹ - 10⁻⁴m）进行浓度 - 反应曲线测定。12名病情稳定的哮喘患者以随机双盲方式进行研究。在基线测量后的两个研究日，患者被随机分配接受氧气（FiO₂ 1.0）或低氧混合气体（FiO₂ 0.15），随后每隔15分钟给予三次递增剂量的雾化沙丁胺醇。在另外两个研究日，给予雾化生理盐水而非沙丁胺醇。在离体支气管中，与低氧相比，高氧和常氧条件下沙丁胺醇诱导的舒张显著更大（P < 0.001），常氧与低氧相比也显著更大（P < 0.01）。在给予雾化沙丁胺醇的低氧和高氧研究日之间，哮喘患者的用力呼气量（FEV₁）自基线起的平均最大变化百分比无显著差异。我们得出结论，急性低氧在体外减弱了气道平滑肌对沙丁胺醇的舒张反应，但对哮喘住院患者中沙丁胺醇诱导的支气管扩张无影响。
