Details

Autor(en) / Beteiligte

• Duncan, Jhodie R
• Garland, Marianne
• Myers, Michael M
• Fifer, William P
• Yang, May
• Kinney, Hannah C
• Stark, Raymond I

Titel

Prenatal nicotine-exposure alters fetal autonomic activity and medullary neurotransmitter receptors: implications for sudden infant death syndrome

Ist Teil von

• Journal of applied physiology (1985), 2009-11, Vol.107 (5), p.1579-1590

Ort / Verlag

Bethesda, MD: Am Physiological Soc

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts; ; Departments of 2 Pediatrics and ; 3 Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York; and ; 4 New England Research Institute, Watertown, Massachusetts Submitted 22 December 2008 ; accepted in final form 1 September 2009 During pregnancy, exposure to nicotine and other compounds in cigarette smoke increases the risk of the sudden infant death syndrome (SIDS) two- to fivefold. Serotonergic (5-HT) abnormalities are found, in infants who die of SIDS, in regions of the medulla oblongata known to modulate cardiorespiratory function. Using a baboon model, we tested the hypothesis that prenatal exposure to nicotine alters 5-HT receptor and/or transporter binding in the fetal medullary 5-HT system in association with cardiorespiratory dysfunction. At 87 (mean) days gestation (dg), mothers were continuously infused with saline ( n = 5) or nicotine ( n = 5) at 0.5 mg/h. Fetuses were surgically instrumented at 129 dg for cardiorespiratory monitoring. Cesarean section delivery and retrieval of fetal medulla were performed at 161 (mean) dg for autoradiographic analyses of nicotinic and 5-HT receptor and transporter binding. In nicotine-exposed fetuses, high-frequency heart rate variability was increased 55%, possibly reflecting increases in the parasympathetic control of heart rate. This effect was more pronounced with greater levels of fetal breathing and age. These changes in heart rate variability were associated with increased 5-HT 1A receptor binding in the raphé obscurus ( P = 0.04) and increased nicotinic receptor binding in the raphé obscurus and vagal complex ( P < 0.05) in the nicotine-exposed animals compared with controls ( n = 6). The shift in autonomic balance in the fetal primate toward parasympathetic predominance with chronic exposure to nicotine may be related, in part, to abnormal 5-HT-nicotine alterations in the raphé obscurus. Thus increased risk for SIDS due to maternal smoking may be partly related to the effects of nicotine on 5-HT and/or nicotinic receptors. nicotinic receptor; serotonin receptor; parasympathetic activity; raphé obscurus; cardiorespiratory function Address for reprint requests and other correspondence: H. C. Kinney, Dept. of Pathology, Enders 1112.1, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (e-mail: Hannah.kinney{at}childrens.harvard.edu ).