Brown R H, Robbins W, Staats P, Hirshman C
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Am J Respir Crit Care Med. 1995 Apr;151(4):1239-43. doi: 10.1164/ajrccm/151.4.1239.
Stimulation of airway irritant receptors produces reflex bronchoconstriction that can be prevented by pretreatment with anticholinergic drugs or local anesthetics delivered by aerosol or intravenously. We compared therapeutic doses of an orally administered local anesthetic, mexiletine hydrochloride, and intravenously administered lidocaine at blocking histamine-induced bronchoconstriction in five basenji-greyhound dogs, using high-resolution computed tomography (HRCT) to directly measure changes in airway size. In the dogs given placebo, a histamine infusion decreased airway area to 61 +/- 2% (mean +/- SEM) of control (p < 0.01). Mexiletine pretreatment completely prevented histamine-induced airway constriction, with an airway area that was 94 +/- 4% of the control value during the histamine infusion (p = 0.07 compared with baseline). Mexiletine serum levels were therapeutic (1.7 +/- 0.3 mg/L). Similarly, pretreatment with lidocaine significantly blunted the airway constriction provoked by intravenous histamine. In lidocaine-pretreated dogs, histamine decreased airway area to 79 +/- 4% of baseline (p < 0.01). As in the case of mexiletine, lidocaine serum levels were also therapeutic (2.4 +/- 0.3 mg/L). Mexiletine was more effective than lidocaine at preventing histamine-induced bronchoconstriction (p = 0.02). These data suggest that orally administered local anesthetics may be useful in preventing irritant-induced bronchoconstriction in humans.
气道刺激感受器的刺激会引发反射性支气管收缩，而通过气雾剂或静脉注射给予抗胆碱能药物或局部麻醉剂进行预处理可预防这种收缩。我们比较了口服局部麻醉剂盐酸美西律和静脉注射利多卡因在阻断五只巴仙吉犬 - 灵缇犬组胺诱导的支气管收缩方面的治疗剂量，使用高分辨率计算机断层扫描（HRCT）直接测量气道大小的变化。给予安慰剂的犬只中，输注组胺使气道面积降至对照值的61±2%（平均值±标准误）（p<0.01）。美西律预处理完全预防了组胺诱导的气道收缩，在输注组胺期间气道面积为对照值的94±4%（与基线相比，p = 0.07）。美西律血清水平处于治疗范围（1.7±0.3 mg/L）。同样，利多卡因预处理显著减轻了静脉注射组胺引起的气道收缩。在利多卡因预处理的犬只中，组胺使气道面积降至基线的79±4%（p<0.01）。与美西律的情况一样，利多卡因血清水平也处于治疗范围（2.4±0.3 mg/L）。在预防组胺诱导的支气管收缩方面，美西律比利多卡因更有效（p = 0.02）。这些数据表明，口服局部麻醉剂可能有助于预防人类刺激性诱导的支气管收缩。
