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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL020864-16
Application #
2838890
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1978-08-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
2000-11-30
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Sica, Anthony L; Zhao, Ning (2006) Heart rate variability in conscious neonatal swine: spectral features and responses to short-term intermittent hypoxia. BMC Physiol 6:5
Sica, Anthony L; Ruggiero, David A; Hundley, Bruce W (2005) The cardiac-related rhythm in preganglionic sympathetic activities of developing piglets. Brain Res 1042:205-13
Ruggiero, D A; Zhao, N; Anwar, M et al. (2004) Organization of the newborn piglets vagal motor complex: insights into integrated autonomic control mechanisms. Auton Neurosci 115:41-53
Sica, Anthony L; Hundley, Bruce W (2004) Hypercapnia induces long-term changes in postganglionic renal nerve activity in the piglet. Auton Neurosci 111:97-109
Sica, Anthony L; Ruggiero, David A; Zhao, Ning et al. (2002) Developmental changes in heart rate variability during exposure to prolonged hypercapnia in piglets. Auton Neurosci 100:41-9
Zhao, Ning; Gootman, Phyllis M; Sica, Anthony L (2002) Baroreceptor-related dysrhythmias in piglets with selective autonomic denervation of the heart. Neurosci Lett 330:79-83
Khan, M S; Zhao, N; Sica, A L et al. (2001) Changes in R-R and Q-T intervals following cardiac vagotomy in neonatal swine. Exp Biol Med (Maywood) 226:32-6
Hundley, B W; Sica, A L; Gootman, P M (2001) Rhythmicities in sympathetic discharge: a signal of cardiorespiratory integration in developing animals. Ann N Y Acad Sci 940:416-30
Zhao, N; Khan, M; Ingenito, S et al. (2001) Electrocardiographic changes during postnatal development in conscious swine with cardiac autonomic imbalance. Auton Neurosci 88:167-74
Ruggiero, D A; Underwood, M D; Mann, J J et al. (2000) The human nucleus of the solitary tract: visceral pathways revealed with an ""in vitro"" postmortem tracing method. J Auton Nerv Syst 79:181-90

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