Despite recent progress in its prevention, the Sudden Infant Death Syndrome (SIDS) remains the most frequent cause of infant mortality between the ages of one month and one year in the United States. A striking epidemiological finding is that more victims than expected are found in the prone position, often with the face in the bedclothes. Campaigns to encourage putting infants to sleep on their backs have led to a gratifying reduction in the incidence of SIDS in several countries, yet the influence of posture remains mysterious. This project will use decerebrate neonatal piglets to explore the possibility that the risk of prone sleeping is determined by reflex responses involving the upper airway, and that these responses may be aggravated by CO2 in the upper airway (from re-breathing), by abnormalities of the ventral medulla (for which there is evidence in some SIDS victims), or from elevated body temperature (for which there is epidemiologic evidence and an intriguing report of a study in puppies). We will examine the influence of each of these conditions on three upper airway reflex responses: the """"""""diving"""""""" response, the laryngeal chemo reflex and the load-compensating reflex response to upper airway obstruction. Our general hypothesis is that some combination of conditions and stimuli will exaggerate the reflex interruption of breathing, possibly contributing to the pathogenesis 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 #
5R01HD042707-04
Application #
7034496
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Willinger, Marian
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2008-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$347,146
Indirect Cost
Name
Dartmouth College
Department
Physiology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Arnal, Ashley V; Gore, Julie L; Rudkin, Alison et al. (2013) Influence of age, body temperature, GABAA receptor inhibition and caffeine on the Hering-Breuer inflation reflex in unanesthetized rat pups. Respir Physiol Neurobiol 186:73-80
Xia, L; Leiter, J C; Bartlett Jr, D (2013) Laryngeal reflex apnea in neonates: effects of CO2 and the complex influence of hypoxia. Respir Physiol Neurobiol 186:109-13
Xia, Luxi; Bartlett Jr, Donald; Leiter, J C (2011) TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets. Respir Physiol Neurobiol 176:21-31
Duy, Philip M; Xia, Luxi; Bartlett Jr, Donald et al. (2010) An adenosine A(2A) agonist injected in the nucleus of the solitary tract prolongs the laryngeal chemoreflex by a GABAergic mechanism in decerebrate piglets. Exp Physiol 95:774-87
Chernov, Mykyta M; Erlichman, Joseph S; Leiter, J C (2010) Ionic mechanisms of central CO(2) chemosensitivity. Respir Physiol Neurobiol 173:298-304
Xia, Luxi; Bartlett Jr, Donald; Leiter, J C (2008) An adenosine A(2A) antagonist injected in the NTS reverses thermal prolongation of the LCR in decerebrate piglets. Respir Physiol Neurobiol 164:358-65
Xia, Luxi; Leiter, James C; Bartlett Jr, Donald (2008) Laryngeal apnea in rat pups: effects of age and body temperature. J Appl Physiol 104:269-74
Leiter, J C; Bohm, Ines (2007) Mechanisms of pathogenesis in the Sudden Infant Death Syndrome. Respir Physiol Neurobiol 159:127-38
Xia, Luxi; Damon, Tracey; Niblock, Mary M et al. (2007) Unilateral microdialysis of gabazine in the dorsal medulla reverses thermal prolongation of the laryngeal chemoreflex in decerebrate piglets. J Appl Physiol 103:1864-72
Bohm, Ines; Xia, Luxi; Leiter, J C et al. (2007) GABAergic processes mediate thermal prolongation of the laryngeal reflex apnea in decerebrate piglets. Respir Physiol Neurobiol 156:229-33

Showing the most recent 10 out of 13 publications