PSYCHOBIOLOGY OF EARLY CARDIO-RESPIRATORY CONTROL

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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.