Carley D W, Trbovic S M, Radulovacki M
Department of Medicine, University of Illinois College of Medicine at Chicago, 60612, USA.
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):917-20. doi: 10.1164/ajrccm.157.3.9710006.
To test the respiratory effects of benzodiazepines in an established animal model of central apnea, we administered nonhypnotic and hypnotic doses of diazepam to nine adult male Sprague-Dawley rats chronically instrumented for sleep staging. In random order on separate days, rats were recorded following intraperitoneal injection of: (1) saline; (2) 0.05 mg/kg diazepam; or (3) 5 mg/kg diazepam. Normalized inspiratory minute ventilation increased significantly during wakefulness and non-rapid eye movement (non-REM) sleep following each dose of diazepam (p < 0.003 in each case) and following the highest dose during rapid eye movement (REM) sleep (p = 0.01). In accord with this respiratory stimulation, non-REM-related spontaneous and post-sigh apnea expression decreased following each dose of diazepam (p = 0.006 to 0.04), but REM-related apnea expression was unaffected despite significant respiratory stimulation. The durations of non-REM and REM sleep were unaffected by the low dose, but following 5 mg/kg of diazepam non-REM sleep was increased (p = 0.03) and REM sleep was decreased (p = 0.009). We conclude that both hypnotic and non-hypnotic doses of benzodiazepines may be associated with suppression of sleep-related central apnea. We further conclude that non-REM and REM-related apneas arise from at least partially distinct mechanisms.
为了在已建立的中枢性呼吸暂停动物模型中测试苯二氮䓬类药物的呼吸效应，我们对9只长期植入睡眠分期监测设备的成年雄性Sprague-Dawley大鼠给予了非催眠剂量和催眠剂量的地西泮。在不同的日子里，按照随机顺序，在腹腔注射以下物质后对大鼠进行记录：(1) 生理盐水；(2) 0.05 mg/kg地西泮；或(3) 5 mg/kg地西泮。在每次给予地西泮后，清醒状态和非快速眼动（非REM）睡眠期间的标准化吸气分钟通气量显著增加（每种情况p < 0.003），在快速眼动（REM）睡眠期间给予最高剂量后也显著增加（p = 0.01）。与这种呼吸刺激一致，每次给予地西泮后，与非REM相关的自发性和叹气后呼吸暂停表现减少（p = 0.006至0.04），但尽管有显著的呼吸刺激，与REM相关的呼吸暂停表现未受影响。低剂量未影响非REM和REM睡眠的时长，但给予5 mg/kg地西泮后，非REM睡眠增加（p = 0.03），REM睡眠减少（p = 0.009）。我们得出结论，催眠剂量和非催眠剂量的苯二氮䓬类药物都可能与睡眠相关中枢性呼吸暂停的抑制有关。我们进一步得出结论，与非REM和REM相关的呼吸暂停至少部分源于不同的机制。
