Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons

Cummings KJ, Commons KG, Fan KC, Li A, Nattie EE. Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons. Am J Physiol Regul Integr Comp Physiol 296: R1783-R1796, 2009. First published April 15, 2009; doi:10.1152/ajpregu.00122.2009.-The medullary 5-HT system has potent effects on heart rate and breathing in adults. We asked whether this system mitigates the respiratory instability and bradycardias frequently occurring during the neonatal period. 5,7-Dihydroxytryptamine (5,7-DHT) or vehicle was administered to rat pups at postnatal day 2 (P2), and we then compared the magnitude of bradycardias occurring with disruptions to eupnea in treated and vehicle control littermates at P5-6 and P10-12. We then used a novel method that would allow accurate assessment of the ventilatory and heart rate responses to near square-wave challenges of hypoxia (10% O-2), hypercapnia (5 and 8% CO2 in normoxia and hyperoxia), and asphyxia (8% CO2-10% O-2), and to the induction of the Hering-Breuer inflation reflex (HBR), a potent, apnea-inducing reflex in newborns. The number of 5-HT-positive neurons was reduced similar to 80% by drug treatment. At both ages, lesioned animals had considerably larger bradycardias during brief apnea; at P5-6, average and severe events were similar to 50% and 70% greater, respectively, in lesioned animals (P = 0.002), whereas at P10-12, events were similar to 23% and 50% greater (P = 0.018). However, lesioning had no effect on the HR responses to sudden gas challenge or the HBR. At P5-6, lesioned animals had reduced breathing frequency and ventilation ((V)over dotE), but normal (V)over dotE relative to metabolic rate ((V)over dotE/(V)over dotO(2)). At P10-12, lesioned animals had a more unstable breathing pattern (P = 0.04) and an enhanced (V)over dotE response to moderate hypercapnia (P = 0.007). Within the first two postnatal weeks, the medullary 5-HT system plays an important role in cardiorespiratory control, mitigating spontaneous bradycardia, stabilizing the breathing pattern, and dampening the hypercapnic (V)over dotE response.