| First Author | Cummings KJ | Year | 2010 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 298 |
| Issue | 5 | Pages | R1333-42 |
| PubMed ID | 20421636 | Mgi Jnum | J:159692 |
| Mgi Id | MGI:4452279 | Doi | 10.1152/ajpregu.00110.2010 |
| Citation | Cummings KJ, et al. (2010) Bradycardia in serotonin deficient Pet-1-/- mice: influence of respiratory dysfunction and hyperthermia over the first two postnatal weeks. Am J Physiol Regul Integr Comp Physiol |
| abstractText | Neonatal rodents deficient in medullary serotonin (5-HT) neurons have respiratory instability and enhanced spontaneous bradycardias. This study asks if in Pet-1-/- mice over development: 1) the respiratory instability leads to hypoxia, 2) greater bradycardia is related to the degree of hypoxia or concomitant hypopnea and 3) hyperthermia exacerbates bradycardias. Pet-1+/+, +/- and -/- mice (P4-5, P11-12, P14-15) were held at normal body temperature (TB) and were then made 2 degrees C hypo- and hyperthermic. Using a pneumotach-mask system with ECG, we measured heart rate (HR), metabolic rate (VO2) and ventilation (VE). We also calculated indices for apnea-induced hypoxia (Total Hypoxia: apnea incidence x O2 consumed during apnea = ul.g-1.min-1) and bradycardia (Total Bradycardia: bradycardia incidence x magnitude = beats missed.min-1). Resting HR was significantly lower in all Pet-1-/- animals, irrespective of TB. At P4-5, Pet-1-/- animals had ~4 to 8-fold greater Total Bradycardia (P<0.001) owing to a ~2 to 3-fold increase in bradycardia magnitude and a near-doubling in bradycardia incidence. Pet-1-/- animals had a significantly reduced VO2 at all TB; thus there was no genotype effect on Total Hypoxia. At P11-12, Total Bradycardia was nearly 3-fold greater in hyperthermic Pet-1-/- animals compared to controls (P<0.01). In both genotypes, bradycardia magnitude was positively related to the degree of hypopnea (P=0.02), but there was no genotype effect on degree of hypopnea or Total Hypoxia. At P14-15, genotype had no effect on Total Bradycardia, but Pet-1-/- animals had up to 7-times more Total Hypoxia (P<0.001), owing to longer and more frequent apneas and a normalized VO2. We infer from these data that 1) Pet-1-/- neonates are probably not hypoxic until P14-15; 2) neither apnea-related hypoxia nor greater hypopnea contribute to the enhanced bradycardias of Pet-1-/- neonates from ~P4 to ~P12; 3) an enhancement of a temperature-sensitive reflex may contribute to the greater bradycardia in hyperthermic Pet-1-/- animals at ~P12. Key words: heart rate, body temperature, breathing, apnea, SIDS. |
