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The Upper Airway and the Sudden Infant Death Syndrome

上呼吸道和婴儿猝死综合症

基本信息

批准号：
8306838
负责人：
DONALD BARTLETT
金额：
$ 39.58万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306838
关键词：
Acetylcholine Adult Animals Apnea Beds Behavior Body Temperature Bradycardia Brain Brain Stem Breathing Cardiovascular system Case-Control Studies Cessation of life Data Defect Deglutition Effectiveness Employee Strikes Epidemiologist Epidemiology Event Fetal Alcohol Exposure Fever Glutamates Grant Heat Losses Human Incidence Infant Infant Mortality Larynx Lead Liquid substance Mediating Milk Neonatal Neonatal Mortality Neuraxis Neurons Neurotransmitter Receptor Neurotransmitters Newborn Animals Nucleus solitarius Oxygen Parents Pathogenesis Physiological Physiology Posture Predisposition Prevention Preventive Process REM Sleep Reflex action Research Personnel Risk Risk Factors Role Serotonin Site Sleep Stomach Content Sudden Death Sudden infant death syndrome Synapses System TRPV1 gene Temperature Testing Time United States Wakefulness Water abstracting design fetal tobacco exposure gamma-Aminobutyric Acid high risk improved insight instrument neurotransmission receptor research study respiratory response success

项目摘要

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.

6.项目总结/摘要在美国，婴儿猝死综合症的发病率大幅下降，由于提倡婴儿仰卧睡觉的教育运动，许多州和其他地方的婴儿都喜欢仰卧睡觉。尽管取得了这一成功，小岛屿发展中国家仍然是婴儿死亡率的主要原因。在预防艾滋病毒/艾滋病方面的进一步进展小岛屿发展中国家可能需要进一步了解其发病机制。喉化学反射（LCR）-呼吸暂停和吞咽反应喉内的水，牛奶或其他液体-是更突出的新生动物与成人相比，婴儿和人类婴儿中的胰岛素水平更高，因此长期以来一直被怀疑是SIDS的原因。在过去的四年中，我们发现，在新生仔猪中，比正常体温高出3摄氏度。体温过高的这种影响是可逆的身体冷却，在同一动物身上重复多次。喉水感受器不受温度在这个范围内变化，但在孤束核区域的延髓局部变暖神经束（NTS），来自喉的传入神经与控制神经元的突触连接呼吸和吞咽，可逆地夸大了LCR，强烈暗示了一个髓质部位的行动，先前证明的全身变暖对LCR的影响。延髓温度对LCR持续时间和强度的影响是一个惊人的新发现。这一发现在SIDS的发病机制中具有极其重要的意义。在此更新申请中，我们将研究这种温度影响的机制，并将其置于与小岛屿发展中国家有关的其他研究结果的背景下。我们将研究去脑仔猪，以确定（1）高温是否会加重喉呼吸暂停，由于GABA（中枢神经系统的主要抑制性神经递质）的过度活动，（2）是否喉呼吸暂停的热加重受到延髓中的操作的影响，神经递质，其受体已被证明是缺乏SIDS婴儿，（3）的行为，在正常和抬高体诱发喉呼吸暂停时孤束核温度敏感神经元的变化温度和（4）TRPV 1通道是否参与喉呼吸暂停的热加重。我们还将研究完整的，长期仪器仔猪在觉醒，NREM和REM睡眠，确定高温和中枢神经系统操作对LCR的联合影响神经传递素在更自然的条件下。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，并可能导致合理的预防措施为SIDS高危人群中的婴儿提供治疗。7.项目叙述婴儿猝死综合症一个看起来健康的婴儿通常在睡眠时是造成婴儿死亡的主要原因，给孩子的父母SIDS的一个可疑机制是胃内容物，进入喉部，引发强烈的反射，停止呼吸，导致缺氧致死我们将研究这种反射和它的增强，新生仔猪的体温，以寻找SIDS易感性的测试方法，对确定为有风险的婴儿进行预防性治疗。