Abraham W M, Stevenson J S, Eldridge M, Garrido R, Nieves L
Division of Pulmonary Diseases, University of Miami, Mount Sinai Medical Center, Miami Beach, Florida 33140.
J Appl Physiol (1985). 1988 Sep;65(3):1062-8. doi: 10.1152/jappl.1988.65.3.1062.
We examined the effects of nedocromil sodium, a new drug developed for the treatment of reversible obstructive airway disease, on allergen-induced early and late bronchial responses and the development of airway hyperresponsiveness 24 h after challenge in nine allergic sheep. On occasions greater than 2 wk apart the sheep were treated with 1) placebo aerosol (buffered saline) before and 3 h after antigen challenge, 2) an aerosol of nedocromil sodium (1 mg/kg in 3 ml buffered saline) before antigen challenge and placebo 3 h after challenge, and 3) placebo aerosol before and nedocromil sodium aerosol 3 h after challenge. Early and late bronchial responses were determined by measuring specific lung resistance (sRL) before and periodically after challenge. Airway responsiveness was assessed by determining from dose-response curves the carbachol concentration (in % wt/vol) that increased sRL to 5 cmH2O/s. In the placebo trial, antigen challenge resulted in early and late increases in sRL over a base line of 353 +/- 32 and 131 +/- 17% (SE), respectively. Both early and late increases in sRL were blocked (P less than 0.05) when the sheep were pretreated with nedocromil sodium. When nedocromil was given after the early response, the late response was reduced significantly. Eight of nine sheep developed airway hyperresponsiveness 24 h after antigen challenge. In these eight sheep, carbachol concentration before antigen challenge was 2.6 +/- 0.3%, 24 h later carbachol concentration was significantly lower (1.8 +/- 0.3%). Both nedocromil sodium treatments blocked (P less than 0.05) this antigen-induced airway hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了用于治疗可逆性阻塞性气道疾病的新药奈多罗米钠，对9只变应性绵羊变应原激发后早期和晚期支气管反应以及激发后24小时气道高反应性发展的影响。在间隔超过2周的不同时间，对绵羊进行如下处理：1）抗原激发前和激发后3小时给予安慰剂气雾剂（缓冲盐水）；2）抗原激发前给予奈多罗米钠气雾剂（3毫升缓冲盐水中含1毫克/千克），激发后3小时给予安慰剂；3）激发前给予安慰剂气雾剂，激发后3小时给予奈多罗米钠气雾剂。通过测量激发前和激发后定期的特异性肺阻力（sRL）来确定早期和晚期支气管反应。通过剂量反应曲线确定使sRL增加到5厘米水柱/秒的卡巴胆碱浓度（重量/体积百分比）来评估气道反应性。在安慰剂试验中，抗原激发导致sRL早期和晚期分别比基线升高353±32%和131±17%（标准误）。当绵羊用奈多罗米钠预处理时，sRL的早期和晚期升高均被阻断（P<0.05）。当在早期反应后给予奈多罗米时，晚期反应显著降低。9只绵羊中有8只在抗原激发后24小时出现气道高反应性。在这8只绵羊中，抗原激发前卡巴胆碱浓度为2.6±0.3%，24小时后卡巴胆碱浓度显著降低（1.8±0.3%）。两种奈多罗米钠处理均阻断了（P<0.05）这种抗原诱导的气道高反应性。（摘要截短至250字）
