Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons.
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% O2), hypercapnia (5 and 8% CO2 in normoxia and hyperoxia), and asphyxia (8% CO2-10% O2), 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 approximately 80% by drug treatment. At both ages, lesioned animals had considerably larger bradycardias during brief apnea; at P5-6, average and severe events were approximately 50% and 70% greater, respectively, in lesioned animals (P = 0.002), whereas at P10-12, events were approximately 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 (Ve), but normal Ve relative to metabolic rate (Ve/Vo2). At P10-12, lesioned animals had a more unstable breathing pattern (P = 0.04) and an enhanced Ve 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 Ve response.
Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
Kevin J
KJ
Cummings
Kathryn G
KG
Commons
Kenneth C
KC
Fan
Aihua
A
Li
Eugene E
EE
Nattie
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000378:metabolism / Q000503:physiopathology; D001237:Asphyxia / Q000378:metabolism / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012120:Respiration Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity*; D013398:Sudden Infant Death
D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin