| Autor: |
Ramanantsoa, N., Vaubourg, V., Matrot, B., Vardon, G., Dauger, S., Gallego, J. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology; Nov2007, Vol. 293, pR2027-R2035, 9p, 4 Charts, 4 Graphs |
| Abstrakt: |
Congenital central hypoventilation syndrome (CCHS) is a rare disease with variable severity, generally present from birth and chiefly characterized by impaired chemosensitivity to hypercapnia. The main cause of CCHS is a mutation in the PHOX2B gene, which encodes a transcription factor involved in the development of automatic medullary reflex pathways. Temperature regulation is abnormal in many patients with CCHS. Here, we examined whether ambient temperature influenced CO2 sensitivity in a mouse model of CCHS. A weak response to CO2 at thermoneutrality (32°C) was noted previously in 2-day-old mice with an invalidated Phox2b allele (Phox2b+/–), compared with wild-type littermates. We exposed Phox2b+/– pups to 8% CO2 at three ambient temperatures (TAs): 29°C, 32°C, and 35°C. We measured breathing variables and heart rate (HR) noninvasively using a novel whole body flow plethysmograph equipped with contact electrodes. Body temperature and baseline breathing increased similarly with TA in mutant and wild-type pups. The hypercapnic ventilatory response increased linearly with TA in both groups, while remaining smaller in mutant than in wild-type pups at all TAs. The differences between the absolute increases in ventilation in mutant and wild-type pups become more pronounced as temperature increased above 29°C. The ventilatory abnormalities in mutant pups were not associated with significant impairments of heart rate control. In both mutant and wild-type pups, baseline HR increased with TA. In conclusion, TA strongly influenced the hypercapnic ventilatory response in Phox2b+/– mutant mice. These findings suggest that abnormal temperature regulation may contribute to the severity of respiratory impairments in CCHS patients. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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