Nicotine delays arousal during hypoxemia in lambs

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 exposur e, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infus ion of nicotine could impair hypoxic arousal through interference with oxyg en-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 co mpared during a control saline infusion and during a 0.5 mu g.kg(-1).min(-1 ) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as w ell as arousal, were defined by EEG, nuchal electromyogram, and electroocul ogram. Each lamb acted as its own control. Arousal from quiet sleep occurre d 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 ve ntilatory response to hypoxia in wakefulness was similar during both condit ions but was significantly attenuated in quiet sleep during nicotine infusi on (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and he art rate responses were similar during both conditions. These results sugge st that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance fur sudden infant death syndrome.