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Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome.
Madani, Amélia; Pitollat, Gabriel; Sizun, Eléonore; Cardoit, Laura; Ringot, Maud; Bourgeois, Thomas; Ramanantsoa, Nelina; Delclaux, Christophe; Dauger, Stéphane; d'Ortho, Marie-Pia; Thoby-Brisson, Muriel; Gallego, Jorge; Matrot, Boris.
Afiliação
  • Madani A; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Pitollat G; Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux, CNRS, Bordeaux, France.
  • Sizun E; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Cardoit L; Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux, CNRS, Bordeaux, France.
  • Ringot M; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Bourgeois T; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Ramanantsoa N; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Delclaux C; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Dauger S; Service d'Explorations Fonctionnelles Pédiatriques and.
  • d'Ortho MP; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Thoby-Brisson M; Service de Médecine Intensive-Réanimation Pédiatriques, Hôpital Robert Debré, AP-HP, Paris, France; and.
  • Gallego J; NeuroDiderot, FHU I2-D2, Université de Paris, Inserm, Paris, France.
  • Matrot B; Service de Physiologie-Explorations Fonctionnelles, Hôpital Bichat, AP-HP, Paris, France.
Am J Respir Crit Care Med ; 204(10): 1200-1210, 2021 11 15.
Article em En | MEDLINE | ID: mdl-34478357
Rationale: Congenital central hypoventilation syndrome (CCHS) is characterized by life-threatening sleep hypoventilation and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation, with patients requiring lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. Objectives: To determine if Phox2b27Ala/+ mice, which present the main symptoms of CCHS and die within hours after birth, also express obstructive apneas, and to investigate potential underlying mechanisms. Methods: Apneas were classified as central, obstructive, or mixed by using a novel system combining pneumotachography and laser detection of abdominal movement immediately after birth. Several respiratory nuclei involved in airway patency were examined by immunohistochemistry and electrophysiology in brainstem-spinal cord preparations. Measurements and Main Results: The median (interquartile range) of obstructive apnea frequency was 2.3 (1.5-3.3)/min in Phox2b27Ala/+ pups versus 0.6 (0.4-1.0)/min in wild types (P < 0.0001). Obstructive apnea duration was 2.7 seconds (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7 seconds (1.1-1.9) in wild types (P < 0.0001). Central and mixed apneas presented similar significant differences. In Phox2b27Ala/+ preparations, the hypoglossal nucleus had fewer (P < 0.05) and smaller (P < 0.01) neurons, compared with wild-type preparations. Importantly, coordination of phrenic and hypoglossal motor activities was disrupted, as evidenced by the longer and variable delay of hypoglossal activity with respect to phrenic activity onset (P < 0.001). Conclusions: The Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also to obstructive and mixed apneas, likely because of hypoglossal dysgenesis. These results thus demand attention toward obstructive events in infants with CCHS.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apneia do Sono Tipo Central / Hipoventilação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Am J Respir Crit Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apneia do Sono Tipo Central / Hipoventilação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Am J Respir Crit Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França País de publicação: Estados Unidos