Central Sleep Apnea : Physiologic Mechanisms to Inform Treatment

Central sleep apnea (CSA) is common in patients with heart failure and those using opioid analgesics. Unfortunately, effective treatment of central apnea remains elusive, pressure therapy given the modest efficiency of positive airway pressure therapy. The focus of this proposal is to identify mechanistic pathways to guide future therapeutic interventions for central sleep apnea based on the strong premise that multi-modality therapy will normalize respiration and hence mitigate adverse long-term consequences of CSA. The investigators' proposed studies will test combination therapies, including positive airway pressure (PAP) plus a pharmacological agent who have heart failure or are using opioid analgesics. The investigators anticipate that findings will inform future clinical trials to improve care and quality of life among Veterans suffering from central sleep apnea, which remains difficult to treat using existing approaches.

Inclusion Criteria: * Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)\>15/hour with CAHI\>5/hour, will be included in the experiments Exclusion Criteria: * less than 18 years old * pregnant or breastfeeding female * have severe respiratory disease that require to be on oxygen * recent health event that may affect the ability to participate in the study, * Body Mass Index (BMI) is \>40 kg/m2 * significant insomnia * mental instability * recent health event that may affect sleep * if at any time the principal investigator (PI) identifies that a certain drug is not suitable, or are unable to use the device that is used to treat sleep apnea, will be not be allowed to participate in the study