Caffeine improves the ability of serotonin-deficient (Pet-1-/-) mice to survive episodic asphyxia

Abstract

In neonatal rodents, serotonin (5-HT) neurons are critical for successful autoresuscitation. We hypothesized that caffeine, a respiratory stimulant, would hasten the onset of gasping and improve autoresuscitation in 5-HT-deficient, Pet-1-/- mice.Methods:Using a head-out system and electrocardiogram, we measured respiratory and heart rate (HR) responses of Pet-1-/- rodents and their littermates during episodic asphyxia at postnatal days 8-9 (P8-9). After a baseline recording, we injected either vehicle or caffeine (i.p.) at doses of 1, 5, or 10 mg/kg. We then induced 10 brief (∼30 s) episodes of asphyxia, each interspersed with 5 min of room air to allow autoresuscitation. In addition to measuring survival, we measured the duration of hypoxic apnea (time to initiate gasping) and time to recover eupnea and HR.Results:Caffeine had a dose-dependent effect of hastening the onset of gasping, recovery of breathing, and restoration of HR in Pet-1-/-(but not in wild-type) rodents, thereby improving survival across asphyxic episodes. Increased survival was strongly correlated with hastened onset of gasping.Conclusion:Our data suggest that caffeine reduces mortality relating to asphyxia and 5-HT deficiency. These findings may be relevant for efforts to reduce the incidence of sudden infant death syndrome (SIDS), given that SIDS is associated with failed autoresuscitation and reduced brainstem 5-HT. © 2013 International Pediatric Research Foundation, Inc.