The Upper Airway and the Sudden Infant Death Syndrome

6. 项目总结/摘要 美国婴儿猝死综合症（SIDS）的发病率大幅下降 各州和其他地方开展了支持婴儿仰卧睡眠姿势的教育活动。 尽管取得了这一成功，SIDS 仍然是婴儿死亡率的一个主要因素。预防工作取得进一步进展 SIDS 可能需要加深对其发病机制的了解。喉化学反射（LCR）-呼吸暂停 对喉内水、牛奶或其他液体的吞咽反应在新生动物中更为突出 人类婴儿的患病率高于成人，因此长期以来一直被怀疑是某些 SIDS 病例的原因。 我们在过去四年中发现，在加热后的新生仔猪中，LCR 被大大夸大了 1- 比正常体温高3℃。体温过高的这种效应可以通过身体冷却来逆转，并且可以 在同一动物身上重复多次。喉部水感受器不受 温度在此范围内变化，但使孤核区域的髓质局部变暖 束（NTS），来自喉部的传入神经与控制神经元的突触连接 呼吸和吞咽，可逆地夸大 LCR，强烈暗示了髓质作用部位 先前已证明全身变暖对 LCR 的影响。 髓质温度对 LCR 持续时间和强度的影响是一个引人注目的新发现 这一发现对于 SIDS 的发病机制具有极其重要的意义。在此续签申请中，我们将 研究这种温度效应的机制，并将其置于与 SIDS 相关的其他研究结果的背景下。我们 将研究去大脑仔猪以确定（1）是否因热疗而加剧喉部呼吸暂停 由于中枢神经系统主要抑制性神经递质 GABA 的过度活性，(2) 喉部呼吸暂停的热夸大是否受到延髓操作的影响 SIDS 婴儿的神经递质受体已被证明存在缺陷，(3) 正常和抬高身体引起喉部呼吸暂停时 NTS 中的温度敏感神经元 温度以及（4）TRPV1 通道是否参与了喉部呼吸暂停的热加剧。 我们还将研究清醒状态、非快速眼动睡眠和快速眼动睡眠期间完整的、长期使用仪器的仔猪，以了解 确定热疗和中枢神经系统操作对 LCR 的综合影响 更自然条件下的神经递质。这些实验的结果将提供关于 温度和神经递质对 LCR 的相互作用，可能会导致合理的预防措施 针对 SIDS 高风险人群的婴儿的治疗。 7. 项目叙述 婴儿猝死综合症 (SIDS) 是指表面健康的婴儿意外死亡 婴儿，通常在睡眠期间是婴儿死亡和毁灭性事件的主要原因 为了宝宝的父母。 SIDS 的一种可疑机制是胃内容物 反流到喉部，引发强烈的反射，导致呼吸停止并导致 因缺氧而死亡。我们将通过增加来检查这种反射及其增强 新生仔猪的体温，以寻找 SIDS 易感性测试 对被确定有风险的婴儿进行预防性治疗。

6. Project Summary/Abstract The incidence of the Sudden Infant Death Syndrome (SIDS) has decreased substantially in the United States and elsewhere as a result of educational campaigns favoring the supine posture for sleeping infants. Despite this success, SIDS remains a major contributor to infant mortality. Further progress in the prevention of SIDS is likely to require improved understanding of its pathogenesis. The laryngeal chemoreflex (LCR)-apnea and swallowing in response to intralaryngeal water, milk or other fluids-is more prominent in newborn animals and human infants than in adults and, therefore, has long been suspected as a cause of some cases of SIDS. We found during the past four years that the LCR is greatly exaggerated in neonatal piglets that are warmed 1- 3 ¿C above their normal body temperatures. This effect of hyperthermia is reversible by body cooling and can be repeated several times in the same animal. The laryngeal water receptors are not influenced by temperature changes in this range, but locally warming the medulla in the region of the nucleus of the solitary tract (NTS), where afferents from the larynx make their synaptic connections with neurons that control breathing and swallowing, reversibly exaggerates the LCR, strongly implying a medullary site of action for the previously demonstrated effect of whole body warming on the LCR. The influence of medullary temperature on the duration and intensity of the LCR is a striking new finding, which is of compelling importance in the pathogenesis of SIDS. In this renewal application, we will study the mechanism of this temperature effect and place it in the context of other findings related to SIDS. We will study decerebrate piglets to determine (1) whether the exaggeration of laryngeal apnea by hyperthermia is due to excessive activity of GABA, the major inhibitory neurotransmitter of the central nervous system, (2) whether the thermal exaggeration of laryngeal apnea is influenced by manipulation in the medulla of neurotransmitters whose receptors have been shown to be deficient in SIDS infants, (3) the behavior of temperature sensitive neurons in the NTS during elicitation of laryngeal apnea at normal and elevated body temperatures and (4) whether TRPV1 channels are involved in the thermal exaggeration of laryngeal apnea.. We will also study intact, chronically instrumented piglets during wakefulness, NREM and REM sleep to determine the combined influence on the LCR of hyperthermia and manipulation of central nervous system neurotransmitters under more natural conditions. The results of these experiments will provide insight about the interactions of temperature and neurotransmitters on the LCR and may lead to rational preventive therapies for infants in groups that are at high risk for SIDS. 7. Project Narrative Sudden Infant Death Syndrome (SIDS)the unexpected death of an apparently healthy baby, usually during sleepis a major cause of infant mortality and a devastating event for the baby's parents. One suspected mechanism of SIDS is that stomach contents, regurgitated into the larynx, trigger a powerful reflex that stops breathing and leads to death from oxygen lack. We will examine this reflex and its enhancement by increased body temperature in neonatal piglets in an effort to find tests for SIDS susceptibility and preventive treatments for infants identified as being at risk.