Delivery of CO2by displacement ventilation for the treatment of sleep apnea

Introduction: In this study, we explore a therapeutic intervention using respiratory gases and a surfactant in a Brown Norway (BN) rat model of central sleep apnea. The BN rat exhibits a high spontaneous sleep apnea index, which is greatly increased following allergen-induced bronchoconstriction. Aims and objectives: To determine if carbon dioxide gas and/or a synthetic nebulized surfactant, Perflubron (PFOB) can treat central sleep apnea in the BN rat model and to determine if they can be delivered non-invasively using displacement ventilation. Methods: A late phase allergic airway response was elicited in ovalbumin-sensitized and challenged BN rats. Apneas were monitored using a non-invasive whole-body barometric plethysmograph. During the late-phase plateau, rats were treated for 10 minutes with one of the following: 8% CO2, 8% CO2 with nebulized perfluorooctylbromide (PFOB), nebulized PFOB, or medical air. Results: PFOB and CO2 inhalation resulted in immediate and sustained decreases in apnea duration. The combination of gases had an additive effect Conclusion: This BN rat model appears to have aspects of both CSA and OSA. CO2 alone and in combination with PFOB, are potent formulations for reducing apneic events following allergen challenge. A novel non-invasive delivery device (figure1B), under development for the treatment of SA, is being tested in this animal model. Funded by AIHS/Pfizer.