{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:41:02Z","timestamp":1788543662139,"version":"build-2803163510"},"reference-count":34,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,4,1]]},"abstract":"<jats:sec><jats:title>Objectives.<\/jats:title><jats:p>Maternal cigarette smoking is established as a major dose-dependent risk factor for sudden infant death syndrome (SIDS). Both prenatal and postnatal exposures to constituents of tobacco smoke are associated with SIDS, but no mechanism of death attributable to nicotine has been found. Breastfeeding gives a substantial increase in absorbed nicotine compared with only environmental tobacco smoke when the mother smokes, because the milk:plasma concentration ratio of nicotine is 2.9 in smoking mothers. Furthermore, many SIDS victims have a slight infection and a triggered immune system before their death, thus experiencing a release of cytokines like interleukin-1\u03b2 (IL-1\u03b2) that may depress respiration. Because apneas in infancy are associated with SIDS, we have tested the hypothesis that postnatal exposure to tobacco constituents and infections might adversely affect an infant's ability to cope with an apneic episode. This is performed by investigating the acute effects of nicotine and IL-1\u03b2 on apnea by laryngeal reflex stimulation and on the subsequent autoresuscitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design.<\/jats:title><jats:p>Thirty 1-week-old piglets (\u00b11 day) were sedated with azaperone. A tracheal and an arterial catheter were inserted during a short halothane anesthesia. The piglets were allowed a 30-minute stabilization period before baseline values were recorded and they were randomized to 4 pretreatment groups (avoiding siblings in the same group): 1) immediate infusion of 10 pmol IL-1\u03b2 intravenously\/kg (IL-1\u03b2 group; n = 8); 2) slow infusion of 5 \u03bcg nicotine intravenously\/kg 5 minutes later (NIC group;n = 8); 3) both IL-1\u03b2 and NIC combined (NIC + IL-1\u03b2 group; n = 6); or 4) placebo by infusion of 1 ml .9% NaCl (CTR group; n = 8). Fifteen minutes later, apnea was induced by insufflation of .1 ml of acidified saline (pH = 2) in the subglottic space 5 times with 5-minute intervals, and variables of respiration, heart rate, blood pressure, and blood gasses were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Stimulation of the laryngeal chemoreflex by insufflation of acidified saline in the subglottic space produced apneas, primarily of central origin. This was followed by a decrease in heart rate, a fall in blood pressure, swallowing, occasional coughs, and finally autoresuscitation with gasping followed by rapid increase in heart rate, rise in blood pressure, and (in the CTR group) an increase of respiratory rate. Piglets pretreated with nicotine had more spontaneous apneas, and repeated spontaneous apneas caused an inability to perform a compensatory increase of the respiratory rate after induced apnea. This resulted in a lower Sao2 than did CTR at 2 minutes after apnea (data shown as median [interquartile range]: 91% [91\u201394] vs 97% [94\u201398]). The pretreatment with IL-1\u03b2 caused prolonged apneas in piglets and an inability to hyperventilate causing a postapneic respiratory rate similar to the NIC. When nicotine and IL-1\u03b2 were combined, additive adverse effects on respiratory control and autoresuscitation compared with CTR were observed: NIC + IL-1\u03b2 had significantly more spontaneous apneas the last 5 minutes before induction of apnea (2 [.3\u20133] vs 0 [0\u20130]). Apneas were prolonged (46 seconds [39\u201351] vs 26 seconds [22\u201331]) and followed by far more spontaneous apneas the following 5 minutes (6.6 [4.0\u20137.9] vs .5 [.2\u2013.9]). Instead of normal hyperventilation after apnea, a dramatic decrease in respiratory rate was seen (at 20 seconds: \u221245% [\u221228 to \u221253] vs +29% [+24\u2013+50], and at 60 seconds: \u221227% [\u221223 to \u221232] vs +3% [\u22122\u2013+6), leading to Sao2below 90% 3 minutes after end of apnea: 89% (87\u201393) versus 97% (95\u201398). These prolonged adverse effects on ventilation were reflected in lowered Pao2, elevated Paco2 and lowered pH 2 minutes, and even 5 minutes, after induction of apnea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>Nicotine interferes with normal autoresuscitation after apnea when given in doses within the range of what the child of a smoking mother could receive through environmental tobacco smoke and breast milk. This is seriously aggravated when combined with the presence of IL-1\u03b2 that is released during infections. This experimental model with piglets may shed light on important mechanisms involved in the cause of SIDS. sudden infant death, apnea, nicotine, interleukines, swine.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.105.4.e52","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:50:41Z","timestamp":1092441041000},"page":"e52-e52","source":"Crossref","is-referenced-by-count":69,"title":["Adverse Effects of Nicotine and Interleukin-1\u03b2 on Autoresuscitation After Apnea in Piglets: Implications for Sudden Infant Death Syndrome"],"prefix":"10.1542","volume":"105","author":[{"given":"J. Frederik","family":"Fr\u00f8en","sequence":"first","affiliation":[{"name":"From the Departments of Pediatric Research and"},{"name":"Obstetrics and Gynecology, Institute of Surgical Research, The National Hospital, University of Oslo; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Akre","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Sleep Related Breathing Disorders Unit, Ullev\u00e5l University Hospital, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babill","family":"Stray-Pedersen","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Institute of Surgical Research, The National Hospital, University of Oslo; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola Didrik","family":"Saugstad","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatric Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2000,4,1]]},"reference":[{"key":"2021121009281833700_B1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1542\/peds.91.5.893","article-title":"Smoking and the sudden infant death syndrome.","volume":"91","author":"Mitchell","year":"1993","journal-title":"Pediatrics"},{"key":"2021121009281833700_B2","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1136\/thx.52.11.1003","article-title":"Passive smoking and sudden infant death syndrome: review of the epidemiological evidence.","volume":"52","author":"Anderson","year":"1997","journal-title":"Thorax"},{"key":"2021121009281833700_B3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1001\/jama.1995.03520340051035","article-title":"The effect of passive smoking and tobacco exposure through breast milk on sudden infant death syndrome.","volume":"273","author":"Klonoff-Cohen","year":"1995","journal-title":"JAMA"},{"key":"2021121009281833700_B4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s004310050805","article-title":"Effects of heavy maternal smoking on intrauterine growth patterns in sudden infant death victims and surviving infants.","volume":"157","author":"Schellscheidt","year":"1998","journal-title":"Eur J Pediatr"},{"key":"2021121009281833700_B5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1651-2227.1999.tb01260.x","article-title":"The amount of brainstem gliosis in sudden infant death syndrome (SIDS) victims correlates with maternal cigarette smoking during pregnancy.","volume":"88","author":"Storm","year":"1999","journal-title":"Acta Paediatr"},{"key":"2021121009281833700_B6","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1651-2227.1992.tb12293.x","article-title":"Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant urine.","volume":"81","author":"Schulte-Hobein","year":"1992","journal-title":"Acta Paediatr"},{"key":"2021121009281833700_B7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1651-2227.1990.tb11430.x","article-title":"Nicotine and cotinine concentrations in the nursing mother and her infant.","volume":"79","author":"Dahlstro\u0308m","year":"1990","journal-title":"Acta Paediatr Scand"},{"key":"2021121009281833700_B8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S0022-3476(85)80427-3","article-title":"Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers.","volume":"107","author":"Luck","year":"1985","journal-title":"J Pediatr"},{"key":"2021121009281833700_B9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1515\/jpme.1994.22.5.421","article-title":"Changes in apnea and autoresuscitation in piglets after intravenous and intrathecal interleukin-1\u03b2 injection.","volume":"22","author":"Stoltenberg","year":"1994","journal-title":"J Perinat Med"},{"key":"2021121009281833700_B10"},{"key":"2021121009281833700_B11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1651-2227.1993.tb12877.x","article-title":"Laryngeal reflex.","volume":"389","author":"Wennergren","year":"1993","journal-title":"Acta Paediatr Suppl"},{"key":"2021121009281833700_B12"},{"key":"2021121009281833700_B13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0022-3476(86)80380-8","article-title":"Pneumograms in infants who subsequently died of sudden infant death syndrome.","volume":"109","author":"Kelly","year":"1986","journal-title":"J Pediatr"},{"key":"2021121009281833700_B14","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1203\/00006450-199204000-00013","article-title":"Sudden infant death syndrome victims show local immunoglobulin M response in tracheal wall and immunoglobulin A response in duodenal mucosa.","volume":"31","author":"Stoltenberg","year":"1992","journal-title":"Pediatr Res"},{"key":"2021121009281833700_B15","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(84)92753-3","article-title":"Overheating and cot death.","volume":"8413","author":"Stanton","year":"1984","journal-title":"Lancet"},{"key":"2021121009281833700_B16","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/bmj.304.6822.277","article-title":"Thermal environment and sudden infant death syndrome: a case-control study.","volume":"304","author":"Ponsonby","year":"1992","journal-title":"Br Med J"},{"key":"2021121009281833700_B17","first-page":"303","article-title":"Effects of increase in body temperature on the breathing pattern in premature infants.","volume":"13","author":"Berterottiere","year":"1990","journal-title":"J Dev Physiol"},{"key":"2021121009281833700_B18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/BF02011601","article-title":"Infant apnea and gastroesophageal reflux.","volume":"22","author":"Gomes","year":"1992","journal-title":"Pediatr Radiol"},{"key":"2021121009281833700_B19","first-page":"217","article-title":"Tracheal occlusion in the newborn piglet: effects of sleep state and occlusion timing on arousal and respiratory responses.","volume":"16","author":"Barrington","year":"1991","journal-title":"J Dev Physiol"},{"key":"2021121009281833700_B20","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0952-8180(96)00138-9","article-title":"Study of the safe threshold of apneic period in children during anesthesia induction.","volume":"8","author":"Xue","year":"1996","journal-title":"J Clin Anesth"},{"key":"2021121009281833700_B21","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1542\/peds.62.5.686","article-title":"Apnea, hypoxemia, and aborted sudden infant death syndrome.","volume":"62","author":"Brady","year":"1978","journal-title":"Pediatrics"},{"key":"2021121009281833700_B22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0022-3476(85)80289-4","article-title":"Control of ventilation in subsequent siblings of victims of sudden infant death syndrome.","volume":"106","author":"Brady","year":"1985","journal-title":"J Pediatr"},{"key":"2021121009281833700_B23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/j.1651-2227.1983.tb09817.x","article-title":"A case of near-miss SIDS developing an abnormal respiratory reaction to hypoxia.","volume":"72","author":"Wennergren","year":"1983","journal-title":"Acta Paediatr Scand"},{"key":"2021121009281833700_B24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/15513819709168348","article-title":"Sudden infant death syndrome: postmortem findings of nicotine and cotinine in pericardial fluid of infants in relation to morphological changes and position of death.","volume":"17","author":"Rajs","year":"1997","journal-title":"Pediatr Pathol Lab Med"},{"key":"2021121009281833700_B25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1651-2227.1994.tb12953.x","article-title":"Nicotine and cotinine levels in pericardial fluid in victims of SIDS.","volume":"83","author":"Milerad","year":"1994","journal-title":"Acta Paediatr"},{"key":"2021121009281833700_B26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0361-9230(95)00073-N","article-title":"Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: Implications for sudden infant death syndrome.","volume":"38","author":"Slotkin","year":"1995","journal-title":"Brain Res Bull"},{"key":"2021121009281833700_B27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/(SICI)1096-9926(199703)55:3<177::AID-TERA2>3.0.CO;2-#","article-title":"Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: implications for perinatal morbidity and mortality, and for sudden infant death syndrome.","volume":"55","author":"Slotkin","year":"1997","journal-title":"Teratology"},{"key":"2021121009281833700_B28","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0034-5687(97)00052-2","article-title":"The cardiorespiratory response to anoxia: normal development and the effect of nicotine.","volume":"109","author":"Schuen","year":"1997","journal-title":"Respir Physiol"},{"key":"2021121009281833700_B29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0034-5687(96)00051-5","article-title":"Effect of nicotine exposure on postnatal ventilatory responses to hypoxia and hypercapnia.","volume":"106","author":"Bamford","year":"1996","journal-title":"Respir Physiol"},{"key":"2021121009281833700_B30","first-page":"361A","article-title":"Nicotine attenuates the ventilatory response to hypoxia in the developing lamb.","volume":"31","author":"Milerad","year":"1992","journal-title":"Pediatr Res"},{"key":"2021121009281833700_B31","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1745-7599.1993.tb00850.x","article-title":"Physiologic effects of maternal smoking on breast-feeding infants.","volume":"5","author":"Stepans","year":"1993","journal-title":"J Am Acad Nurse Pract"},{"key":"2021121009281833700_B32","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1001\/jama.280.2.152","article-title":"Nicotine metabolism and intake in black and white smokers.","volume":"280","author":"Pe\u0301rez-Stable","year":"1998","journal-title":"JAMA"},{"key":"2021121009281833700_B33","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1182\/blood.V77.8.1627.1627","article-title":"Interleukin-1 and interleukin-1 antagonism.","volume":"77","author":"Dinarello","year":"1991","journal-title":"Blood"},{"key":"2021121009281833700_B34","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1651-2227.1998.tb01544.x","article-title":"Are elevated cerebrospinal fluid levels of IL-6 in sudden unexplained deaths, infectious deaths and deaths due to heart\/lung disease in infants and children due to hypoxia?","volume":"87","author":"Vege","year":"1998","journal-title":"Acta Paediatr"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/105\/4\/e52\/843132\/e52.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/105\/4\/e52\/843132\/e52.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T05:34:21Z","timestamp":1682746461000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/105\/4\/e52\/65817\/Adverse-Effects-of-Nicotine-and-Interleukin-1-on"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,4,1]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2000,4,1]]},"published-print":{"date-parts":[[2000,4,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.105.4.e52","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[2000,4,1]]}}}