Breathing resumes within one to two minutes following fentanyl overdose induced apnea in spontaneously breathing rats. As this regular rhythm is produced at a time wherein fentanyl concentrations and receptor occupancy are likely to be extremely high, the mechanisms initiating and sustaining such a respiratory activity remain unclear. Forty-four un-anesthetized adult rats were studied in an open-flow plethysmograph. Regardless of the dose of fentanyl that was used, i.e. 50 μg.kg-1 (n = 8), 100 μg.kg-1 (n = 8) or 300 μg.kg-1 (n = 7), all rats developed an immediate central apnea followed by a depressed regular rhythm that was produced 118, 97 and 81 s (median) later, respectively. Only one rat did not recover. This inspiratory and regular activity consisted of a low frequency and tidal volume pattern with a significant reduction in V̇E/V̇CO2 ratio, which persisted for at least 30 min and that was not different between 100 or 300 μg.kg-1. The time at which this respiratory rhythm emerged, following the highest dose of fentanyl, was not affected by 100 % O2 or 8% CO2/15 % O2. The absolute level of ventilation was however higher in hypercapnic and moderately hypoxic conditions than in hyperoxia. When a second injection of the highest dose of fentanyl (300 μg.kg-1) was performed at 10 min, ventilation was not significantly affected and no apnea was produced in major contrast to the first injection. When a similar injection was performed 30 min after the first injection, in a separate group of rats, an apnea and breathing depression was produced in 30 % of the animals, while in the other rats, ventilation was unaffected. We conclude that the depressed regular respiratory activity emerging during and following fentanyl overdose is uniquely resistant to fentanyl.

中文翻译：

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芬太尼过量后出现阿片类药物抗性呼吸节律的证据。

芬太尼过量导致自主呼吸大鼠呼吸暂停后，呼吸会在 1 到 2 分钟内恢复。由于这种规律的节律是在芬太尼浓度和受体占有率可能极高的时候产生的，因此启动和维持这种呼吸活动的机制尚不清楚。在开放式体积描记器中研究了 44 只未麻醉的成年大鼠。无论使用的芬太尼剂量如何，即 50 μg.kg-1 (n = 8)、100 μg.kg-1 (n = 8) 或 300 μg.kg-1 (n = 7)，所有大鼠均发育立即发生中枢性呼吸暂停，随后分别在 118、97 和 81 秒（中位数）后出现低沉的规律节律。只有一只老鼠没有康复。这种吸气和规律活动包括低频和潮气量模式，V̇E/V̇CO2 比值显着降低，持续至少 30 分钟，并且在 100 或 300 μg.kg-1 之间没有差异。在最高剂量的芬太尼之后出现这种呼吸节律的时间不受 100% O2 或 8% CO2/15% O2 的影响。然而，高碳酸血症和中度缺氧条件下的绝对通气水平高于高氧条件。当在 10 分钟时第二次注射最高剂量的芬太尼 (300 μg.kg-1) 时，与第一次注射相比，通气没有受到显着影响，并且没有产生呼吸暂停。在第一次注射后 30 分钟进行类似注射时，在另一组大鼠中，30% 的动物出现呼吸暂停和呼吸抑制，而在其他大鼠中，通气不受影响。