Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Department of Pharmaceutical Sciences, Lebanese American University, Beyrouth, Lebanon.
J Physiol. 2018 Jul;596(13):2521-2545. doi: 10.1113/JP275866.
The retrotrapezoid nucleus (RTN) drives breathing proportionally to brain PCO2 but its role during various states of vigilance needs clarification. Under normoxia, RTN lesions increased the arterial PCO2 set-point, lowered the PO2 set-point and reduced alveolar ventilation relative to CO production. Tidal volume was reduced and breathing frequency increased to a comparable degree during wake, slow-wave sleep and REM sleep. RTN lesions did not produce apnoeas or disordered breathing during sleep. RTN lesions in rats virtually eliminated the central respiratory chemoreflex (CRC) while preserving the cardiorespiratory responses to hypoxia; the relationship between CRC and number of surviving RTN Nmb neurons was an inverse exponential. The CRC does not function without the RTN. In the quasi-complete absence of the RTN and CRC, alveolar ventilation is reduced despite an increased drive to breathe from the carotid bodies.
The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO homeostasis and breathing during sleep or wake. RTN Nmb-positive neurons were killed with targeted microinjections of substance P-saporin conjugate in adult rats. Under normoxia, rats with large RTN lesions (92 ± 4% cell loss) had normal blood pressure and arterial pH but were hypoxic (-8 mmHg PaO ) and hypercapnic (+10 mmHg ). In resting conditions, minute volume (V ) was normal but breathing frequency (f ) was elevated and tidal volume (V ) reduced. Resting O consumption and CO production were normal. The hypercapnic ventilatory reflex in 65% FiO had an inverse exponential relationship with the number of surviving RTN neurons and was decreased by up to 92%. The hypoxic ventilatory reflex (HVR; FiO 21-10%) persisted after RTN lesions, hypoxia-induced sighing was normal and hypoxia-induced hypotension was reduced. In rats with RTN lesions, breathing was lowest during slow-wave sleep, especially under hyperoxia, but apnoeas and sleep-disordered breathing were not observed. In conclusion, near complete RTN destruction in rats virtually eliminates the CRC but the HVR persists and sighing and the state dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in V but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnoea during slow-wave sleep, even under hyperoxia.
梯形核(retrotrapezoid nucleus, RTN) 按比例驱动呼吸与脑 PCO2 相关，但在不同警觉状态下的作用尚需阐明。在常氧条件下，RTN 损伤增加了动脉 PCO2 设定点，降低了 PO2 设定点，并减少了肺泡通气相对于 CO 生成。潮气量减少，呼吸频率在觉醒、慢波睡眠和 REM 睡眠期间增加到相当程度。RTN 损伤在睡眠期间不会导致呼吸暂停或呼吸紊乱。RTN 损伤在大鼠中几乎消除了中枢呼吸化学感受器反射 (central respiratory chemoreflex, CRC)，同时保留了对缺氧的心肺反应；CRC 与存活 RTN Nmb 神经元数量之间的关系呈负指数关系。没有 RTN，CRC 就无法发挥作用。在 RTN 和 CRC 几乎完全缺失的情况下，尽管颈动脉体的呼吸驱动增加，但肺泡通气仍然减少。
梯形核 (retrotrapezoid nucleus, RTN) 是中枢呼吸化学感受器反射 (CRC) 的几个中枢核之一，以各种能力 (如 CO 检测、神经元调节) 对其做出贡献。在这里，我们测试 RTN 对睡眠或觉醒时 PCO2 稳态和呼吸的重要性。成年大鼠用神经激肽原酶 - 苏氨酸蛋白水解酶 (substance P-saporin conjugate) 靶向微注射杀死 RTN 中的 Nmb 阳性神经元。在常氧条件下，RTN 损伤较大的大鼠 (92 ± 4%细胞丢失) 血压和动脉 pH 值正常，但存在低氧 (-8 mmHg PaO2) 和高碳酸血症 (+10 mmHg)。在静息状态下，分钟通气量 (V) 正常，但呼吸频率 (f) 升高，潮气量 (V) 减少。静息耗氧量和 CO 生成正常。65%FiO2 下的高碳酸血症性通气反射与存活 RTN 神经元的数量呈负指数关系，降低幅度高达 92%。RTN 损伤后，缺氧性通气反射 (hypoxic ventilatory reflex, HVR; FiO2 21-10%) 持续存在，缺氧诱导的叹息正常，缺氧诱导的低血压减轻。在 RTN 损伤的大鼠中，慢波睡眠期间呼吸最低，尤其是在高氧条件下，但未观察到呼吸暂停和睡眠呼吸紊乱。结论：在大鼠中，几乎完全破坏 RTN 几乎消除了 CRC，但 HVR 持续存在，叹息和呼吸的状态依赖性不变。在常氧条件下，RTN 损伤不会改变 V，但至少会降低 21%的肺泡通气量，可能是由于生理无效腔增加所致。RTN 损伤在慢波睡眠期间不会导致睡眠呼吸暂停，即使在高氧条件下也是如此。
