POSTNATAL MATURATION OF CARDIOVASCULAR REGULATORY SYSTEM

点击翻译按钮获取中文摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Expression of coherence (i.e. correlated periodicities in neural signals) is known to appear in an age-related manner, and is taken as evidence of a neural oscillator. Coherence of sympathetic nerve discharge (SND) in developing swine will be explored using neurophysiologic and neuroanatomic techniques. The investigators will determine the validity of the following Hypotheses concerned with development of coherence of SND: specifically: 1) coherence of SND will show an age-related cephalo- caudal gradient with a pre-postganglionic lag, 2) coherence is a function of linkages of brainstem emergent networks, 3) baroreceptor and inspiratory network inputs are involved in the appearance of coherent periodicities, and 4) major sites of the brainstem CV regulatory system can be located through the use of transection of the neuraxis, and field and single neuron recordings. Knowledge of the proper sequence in the development of SND periodicities and the onset of coherence may be of clinical importance if lack of such coordinated activity fails to occur and prevents the neonate from responding to stresses in an integrated age-related pattern. These hypotheses will be tested in Saffan anesthetized piglets (less than 1 day - 3 months of age). The discharge of at least two sympathetic nerves (splanchnic, cervical sympathetic, peroneal, lumbar, renal) will be recorded simultaneously with phrenic activity (monitor of the respiratory pattern generator) and will include denervation of vagi and carotid sinus nerves and specific transections of the neuraxis including the spinal cord. Identification of the CV regulatory system will involve the following progression: a) determination of brainstem sites expressing Fos to baroreceptor/chemoreceptor manipulations, b) CV (heart rate, aortic pressure, regional arterial blood flows) and SND responses to chemical stimulation of the c-fos identified sites, c) phenotypic expression of neurons within these functionally identified regions. The rhythms in SND (1-2 Hz [respiratory modulated], 3-6 Hz (usually cardiac modulated) and 8-13 Hz ("10 Hz rhythm") will be used as markers for identification of neurons comprising- sympathetic brainstem circuits (by correlating population recording and single neuron activity to SND including the mathematical technique of partialization of power and coherence spectra to identify patterns of connectivity). Age- related changes will be identified by statistical analyses of results from the different age groups. The results of these studies should establish developmental changes in sympathetic periodicities as markers of postnatal maturity of the regulatory system and support the hypotheses concerning the importance of onset of coherence in SND as a major sign of postnatal maturation. The aforementioned experiments should help chose among the various explanations of sympathetic rhythmicity and help in the understanding of the most vulnerable period in the life of the child as well as define a possible mechanism in the etiology of SIDS.