Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: Implications for sudden infant death syndrome
Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: Implications for sudden infant death syndrome
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DOI：
10.1523/jneurosci.1918-04.2004
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发表时间：
2004-10-20
影响因子：
5.3
通讯作者：
Mendelowitz, D
中科院分区：
文献类型：
--
作者：
Neff, RA;Simmens, SJ;Mendelowitz, D
母亲吸烟和产前尼古丁暴露是婴儿猝死综合征（SIDS）的最高危险因素。在缺氧时，呼吸频率和心率短暂增加，随后下降。这些双相心肺反应通常通过减少心脏和呼吸肌的代谢需求来延长缺氧时的生存时间。然而，对缺氧的过度反应可能危及生命，并与小岛屿发展中国家有关。心率主要由脑干神经节前心脏抑制迷走神经神经元（CVNs）的活动决定。我们开发了一种体外大鼠脑干切片制剂，该制剂维持有节奏的吸气相关活动，并含有荧光标记的cvn。使用膜片钳电生理技术检测CVNs的突触输入。缺氧引起CVNs中gaba能和甘氨酸能IPSC频率的双相变化，包括IPSC频率的初始增加和随后的减少。产前暴露于尼古丁改变了gabaergy对缺氧的反应，从双相反应到自发性gabaergy IPSC频率的急剧下降。本研究建立了心率对缺氧反应的可能神经化学机制，以及产前尼古丁暴露与缺氧期间过度心动过缓之间的联系，这可能导致小岛屿发展中国家。
Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome ( SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.