Nicotine delays arousal during hypoxemia in lambs

Pediatr Res. 2000 May;47(5):646-52. doi: 10.1203/00006450-200005000-00015.


A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Suckling
  • Arousal / drug effects*
  • Blood Gas Analysis
  • Electroencephalography
  • Electromyography
  • Electrooculography
  • Hemodynamics / drug effects
  • Hyperoxia / blood
  • Hypoxia / blood
  • Hypoxia / metabolism*
  • Infusions, Intravenous
  • Nicotine / administration & dosage
  • Nicotine / blood
  • Nicotine / pharmacology*
  • Reaction Time / drug effects
  • Respiration / drug effects
  • Sheep
  • Sleep / drug effects


  • Nicotine