Prolonged apneas and hypoxia mediated by nicotine and endotoxin in piglets.
OBJECTIVE
Infections and maternal smoking are risk factors for SIDS, and toxins from common bacteria have been proposed as a causative link between infections and SIDS. Nicotine can be transferred in significant amounts postnatally to the infant through environmental tobacco smoke or maternal smoking before nursing. We investigated the acute effects of nicotine and endotoxin on repeated apnea by laryngeal reflex stimulation and the following autoresuscitation.


METHODS
Thirty-four 1-week-old (+/- 1 day) piglets were sedated and randomized to 1 of 4 pretreatment groups: (1) 1 microg endotoxin i.v./kg; (2) 5 microg nicotine i.v./kg; (3) 1 microg endotoxin i.v./kg and 5 microg nicotine i.v./kg, and (4) placebo. Apnea was induced by insufflation of 0.1 ml of acidified saline (pH 2) in the subglottic space of the trachea three times with intervals of 2 min.


RESULTS
Pretreatment with endotoxin caused a significant increase in plasma TNF-alpha in the endotoxin groups (mean value +/- SEM 953 +/- 246 and 980 +/- 226 pg/ml, respectively) but no significant change in plasma IL-1 beta. Blood pressure, respiratory rate or S(a)O(2) was not significantly affected before induced apnea. Both pretreatment with nicotine and endotoxin caused prolonged apneas by 35-45%, a complete loss of normal hyperventilation during autoresuscitation, and prolonged hypoxia after apnea.


CONCLUSIONS
Nicotine and endotoxin interferes with autoresuscitation after apnea. This experimental model on piglets may shed light over important mechanisms involved in the causation of SIDS.
Frøen
J Frederik
JF
Department of Pediatric Research, The National Hospital, University of Oslo, Norway. j.f.froen@klinmed.uio.no
Akre
Harriet
H
Stray-Pedersen
Babill
B
Saugstad
Ola Didrik
OD
D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000139:chemically induced*; D004195:Disease Models, Animal; D004357:Drug Synergism; D000860:Hypoxia / Q000139:chemically induced*; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D010100:Oxygen / Q000097:blood; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine; D013553:Swine Diseases / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D007375:Interleukin-1; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine; D010100:Oxygen