The Upper Airway and the Sudden Infant Death Syndrome

6.项目摘要/摘要 在美国，婴儿猝死综合症(SID)的发病率大幅下降 各州和其他地方开展了有利于婴儿睡姿的教育运动。 尽管取得了这一成功，但小岛屿发展中国家仍然是婴儿死亡率的主要贡献者。在预防疟疾方面取得进一步进展 小岛屿发展中国家可能需要更好地了解其发病机制。喉部化学反射-呼吸暂停 和吞咽对咽内水、牛奶或其他液体的反应-在新生的动物中更为突出 与成人相比，婴儿和人类的发病率更高，因此，长期以来一直被怀疑是导致一些小岛屿发展中国家的原因。 我们在过去的四年中发现，在新生的仔猪中，LCR被极大地夸大了。 比正常体温高出3摄氏度。这种体温过高的效应通过身体降温是可逆的，可以 在同一动物身上重复几次。喉部水感受器不受 温度在此范围内变化，但局部加温孤束核区域的延髓 束(NTS)，来自喉部的传入神经元在这里与控制 呼吸和吞咽，可逆地夸大LCR，强烈暗示着 先前证明了全身变暖对LCR的影响。 髓内温度对LCR持续时间和强度的影响是一个引人注目的新发现 这一发现在小岛屿发展中国家的发病机制中具有极其重要的意义。在此续期申请中，我们将 研究这种温度效应的机制，并将其放在与小岛屿发展中国家有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)高温是否夸大了喉部呼吸暂停 由于中枢神经系统的主要抑制性神经递质GABA活性过高，(2) 延髓推拿是否影响喉呼吸暂停的热夸张 神经递质，其受体已被证明在婴儿缺乏，(3)行为 正常和升高体诱发喉呼吸暂停时NTS内的温度敏感神经元 (4)TRPV1通道是否参与了喉呼吸暂停的热效应。 我们还将研究清醒、NREM和REM睡眠期间完整的、慢性仪器化的小猪 确定热疗和中枢神经系统手法对LCR的联合影响 神经递质在更自然的条件下。这些实验的结果将为我们提供关于 温度和神经递质在LCR上的相互作用可能导致合理的预防 针对婴儿猝死高危人群的治疗。7.项目叙事 婴儿猝死综合征(SIDS)指的是看似健康的人的意外死亡 婴儿，通常在睡眠时是婴儿死亡的主要原因和毁灭性事件 给孩子的父母。小儿麻痹症的一种可能机制是胃内容物， 回流到喉部，引发强烈的反射，停止呼吸，导致 死于缺氧。我们将检查这种反射，并通过增加 新生仔猪的体温，以努力找到婴儿猝死综合征易感性和 对被确定为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.