Using neonatal swine as our animal model of sudden infant death syndrome (SIDS), we will investigate (using both acute and chronic preparations): 1) postnatal differences in innervation of the heart by vagal and postganglionic sympathetic motoneurons, 2) the role of cardiac arrhythmias and the effects of selected visceral afferent stimulation in the etiology of SIDS, 3) the effects of different combinations of autonomic denervation of the heart on survival. In addition, chronic animals, either sham operated or denervated, will be studied under different conditions including such stresses as feeding, temperature changes or hypoxia. These denervation studies will allow the determination of the importance of innervation postnatally. The results of the experimentally induced laterality of sympathetic and/or vagal dominance will verify the importance of balanced innervation of the heart. In the acute preparation we will also examine the effects of denervation on: 1) the ventricular fibrillation threshold and 2) responses to stimulation of visceral afferents, e.g., cardiopulmonary, J-receptor and chemoreceptor. Finally, to examine postnatal maturation of autonomic regulation of the heart and, therefore, of times of greatest susceptibility to arrhythmias, we will obtain motoneurons in the ventrolateral nucleus ambiguous in order to determine: 1) their changing pattern of activity with age, 2) their responses to afferent inputs. and 3) whether their evoked responses are age-related. These experiments will also supply the needed information concerning the role of cardiac arrhythmias in SIDS as well as document the suitability of neonatal swine as an animal model for this disease. The chronic animals will be prepared under sterile operating conditions; vascular access ports will be implanted for blood sampling and pressure measurements while fine wire electrodes will be inserted into the diaphragm for monitoring of respiratory function; the EKG will be recorded from needle electrodes. Acute experiments will be performed under Saffan anesthesia. The aforementioned chronic and acute experiments should supply much needed information regarding the importance of changing autonomic regulation of the heart in the etiology of SIDS.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028931-03
Application #
3330441
Study Section
Special Emphasis Panel (SRC (SI))
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
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; Gootman, P M; Ingenito, S et al. (1999) The area postrema of newborn swine is activated by hypercapnia: relevance to sudden infant death syndrome? J Auton Nerv Syst 76:167-75

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