PSYCHOBIOLOGY OF EARLY CARDIO-RESPIRATORY CONTROL

早期心肺控制的心理生物学

• 批准号: 3330454
• 负责人: HARRY N SHAIR
• 金额: $ 21.06万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3330454
• 关键词: aging; animal infant mortality; aorta; arrhythmia; behavior; blood chemistry; breast feeding; carbon dioxide; carotid sinus; denervation; disease /disorder model; disease /disorder proneness /risk; dissection; heart function; laboratory rat; model design /development; nerve; parent offspring interaction; physiology; postmortem; psychobiology; respiratory function; respiratory oxygen; sudden infant death syndrome

Surgical denervation of chemo and baroreceptors in rats less than two weeks of age leads to profound state dependent abnormalities in cardio- respiratory function and a high incidence of unexplained death. The high mortality induced by these nerve sections is not found if surgery is performed after about two weeks of age. The combination of both an age dependent mortality which is confined to the neonatal period and the physiological consequences of these denervations make this procedure of great potential use for illuminating mechanisms that may be involved in SIDS. The long term objectives of the project are to develop an model of SIDS that would be used in several ways. First, as a model in which to test the feasibility of hypotheses concerning possible mediators of SIDS. If certain chains of events are hypothesized to lead to death in human infants, finding that similar sequences of events are linked to death in animals provides strong support for the validity of the hypothesis. Second, as physiologic and behavior predictor of vulnerability emerge from the animal studies, it would be clearly warranted to add these variables to prospective human studies. Finally, as the mechanisms accounting for death in the animals become clear, therapeutic intervention can be readily tested and if successful may promote similar trials in humans. The proposed studies, which are divided into four phases of experiments, represent a biobehavioral approach to the further study of this model. In the first phase of the research, using established micro-surgical techniques, the age dependency of the effects of carotid sinus and aortic depressor nerve sections will be thoroughly investigated. Although the remaining experiments are not dependent upon a particular outcome of these studies they will greatly improve understanding of the relative importance of these two sensory nerves for the observed effects. Next, using intensive behavioral observation and physiologic recording techniques, the behavioral circumstances surrounding the death of denervated animals will be established and the cardio-respiratory events associated with death will be verified. In addition, detailed postmortem examinations and tissue processing will provide the information required to determine the proximal cause of death. The third phase of the research is comprised of a series of studies investigating the cardio-respiratory and behavioral arousal responses of nerve sectioned animals to increases in carbon dioxide and decreases in oxygen. In other experiments included in this aim, effects of environmental temperature, suckling and feeding, and vibrotactile response will be measured. These experiments will provide new information about the development of critical control and response mechanisms. These experiments will provide new information about the development of critical control and response mechanisms. They are also designed to elucidate the reasons why some animals are resistant to the effect of this surgical procedure. Finally, the experiments in encompassed under our fourth aim will define how environmental factors and experiences that are thought to be important risk factors for SIDS influence maturation of cardio- respiratory regulatory and control mechanisms and, in turn, vulnerability to CSAD nerve sections. Experimental production of prenatal hypoxia manipulations of postnatal weight gain will be the first factors studied.

大鼠化学感受器和压力感受器的手术去神经 周的年龄导致严重的状态依赖性异常，在心脏， 呼吸功能和不明原因死亡的高发生率。 高 如果外科手术是安全的， 在大约两周后进行。 年龄和 受抚养人死亡率，仅限于新生儿期， 这些去神经的生理后果使得这个过程 很大的潜在用途，为照明机制，可能涉及 婴儿猝死综合症。 该项目的长期目标是制定一个小岛屿发展中国家模型 有多种用途。 首先，作为一个模型， 关于小岛屿发展中国家可能调解人的假设的可行性。 如果 某些连锁事件被假设为导致人类死亡 婴儿，发现类似的事件序列与死亡有关， 动物为这一假设的有效性提供了有力的支持。 其次，随着脆弱性的生理和行为预测出现， 根据动物研究，显然有必要添加这些 前瞻性人类研究的变量。 最后，作为机制， 动物死亡的原因变得清晰， 干预措施很容易得到检验，如果成功， 人体试验 拟议的研究分为四个阶段的实验， 代表了进一步研究该模型的生物行为方法。 在第一阶段的研究中，使用已建立的显微外科 技术，颈动脉窦和主动脉的影响的年龄依赖性 将彻底研究减压神经切片。 虽然 其余的实验不依赖于特定的结果， 这些研究将大大提高对相对 这两种感觉神经对观察到的效果的重要性。 接下来，使用密集的行为观察和生理记录 技术，围绕死亡的行为环境， 将建立去神经动物，并观察心肺事件 与死亡有关的证据将被核实 此外，详细的尸检 检查和组织处理将提供所需的信息 以确定近端死因 研究的第三阶段包括一系列的研究 研究心肺和行为唤醒反应， 神经切片动物增加二氧化碳和减少 氧气 在包括在该目标中的其他实验中， 环境温度、哺乳和喂养以及振动触觉 回应将被衡量。 这些实验将提供新的 关键控制和响应的发展信息 机制等 这些实验将提供有关 关键控制和反应机制的发展。 他们也是 旨在阐明为什么有些动物对 这一外科手术的效果。 最后，我们的第四个目标所包含的实验将定义 环境因素和经历如何被认为是 SIDS的重要危险因素影响心血管系统的成熟， 呼吸调节和控制机制，反过来，脆弱性 CSAD神经切片 产前缺氧的实验性生产 产后体重增加的操作将是研究的第一个因素。