Department of Biomedical Sciences, University of Missouri, Columbia, Missouri.
J Appl Physiol (1985). 2013 Dec;115(12):1733-41. doi: 10.1152/japplphysiol.00970.2013. Epub 2013 Oct 17.
In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9-10 or 11-13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using "head-out" plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume (P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls (P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls (P = 0.017), despite the same drop in HR (P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency (P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.
在新生啮齿动物中,脑干部位血清素(5-羟色胺,5-HT)在子宫内或出生时的缺失会损害缺氧诱导的喘息,以及再氧合时(即自主复苏)心率(HR)和呼吸的恢复。急性脑干部位 5-HT 含量缺失后平均动脉压(MAP)如何受到影响尚不清楚。我们假设,脑干部位 5-HT 缺失约 1 天会在发作性缺氧期间损害 MAP。我们向新生大鼠(出生后第 9-10 天或第 11-13 天,22 只治疗组,24 只对照组)腹腔内注射 6-氟色氨酸(20mg/kg),导致脑干部位 5-HT 缺失约 70%。新生大鼠接受了最多 15 次缺氧发作,每次发作之间用 5 分钟的空气间隔以允许自主复苏。在较年幼的大鼠中,我们使用“头外” plethysmography 测量呼吸频率和潮气量,并从心电图测量 HR。在年长的大鼠中,我们使用全身 plethysmography 来检测喘息,同时监测 MAP。确定每次发作后的喘息潜伏期和呼吸、HR 和 MAP 恢复所需的时间。尽管正常的喘息潜伏期、呼吸频率和更大的潮气量(P<0.001),5-HT 缺乏的大鼠存活的发作次数只有对照组的一半(P<0.001)。5-HT 缺乏的大鼠缺氧引起的 MAP 下降是对照组的两倍(P=0.017),尽管 HR 下降相同(P=0.48)。MAP 恢复因 5-HT 缺乏而延迟约 10 秒(P=0.001)。我们的数据表明,脑干部位 5-HT 的缺失会导致对发作性缺氧的显著、过早的 MAP 丧失。这些数据可能有助于解释为什么一些婴儿猝死综合征病例在明显严重缺氧时似乎死于心血管崩溃。