Basic Science

The CISRE has provided:

Fundamental insights into pathogenic mechanisms of obstructive sleep apnea in severe obesity.

     In collaborative studies between pulmonary medicine, sleep medicine and bariatric surgery groups, recent publications demonstrate that obesity produces twin defects in the mechanical and neuromuscular control of pharyngeal collapsibility during sleep. CISRE facilities and personnel were utilized to deploy sophisticated experimental paradigms for measuring pharyngeal collapsibility during sleep. The findings have significant implications for predicting resolution of sleep apnea in response to medical and surgical weight loss.

Significant perspective on long-term effects of sleep apnea on cardiovascular risk profiles.

     In a series of mechanistic studies, investigators in sleep and pulmonary medicine and endocrinology have demonstrated that acute physiologic perturbations in sleep architecture and gas exchange produce pronounced disturbances in glucose homeostasis. To accomplish these studies, investigators utilized the CISRE’s state-of-the-art sleep laboratory to induce and quantify disturbances in sleep and oxygenation along with the adjoining blood processing and monitoring facilities in the Clinical Research Unit. These findings suggest that sleep apnea promotes the development of diabetes mellitus and/or exacerbates glucose intolerance in patients with pre-existing diabetes mellitus.

New understanding about the impact of sleep disordered breathing on cardiovascular disease.

     A series of nocturnal studies in patients with heart failure has demonstrated an exceedingly high prevalence of sleep disordered breathing in this population, and evidence that sleep disordered breathing and, specifically, intermittent hypoxemia produces significant nocturnal hemodynamic and metabolic stress, as reflected by acute responses in circulating biomarkers (brain natriuretic peptide and free fatty acids, respectively). These studies relied upon dedicated CISRE staff and facilities, which provided frequent venous sampling throughout the night. These studies serve to establish acute stress biomarkers as surrogates for long-term cardiovascular stress in vulnerable patients populations.

Groundbreaking studies establishing distinct nocturnal “phenotypes” of sleep disordered breathing in patients with and without COPD.

     The CISRE has provided an experimental “home” for sophisticated physiologic monitoring systems, which have been utilized to establish unique mechanisms of sleep disordered breathing in COPD and to pilot a novel therapy with transnasal insufflation for unloading the respiratory system during sleep.

Sleep apnea in young abstinent recreational MDMA (“ecstasy”) consumers.

     A series of studies in individuals who have been exposed to the brain serotonin neurotoxin and drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) have revealed that abstinent MDMA users have altered sleep architecture, that alterations in sleep are related to reductions in brain serotonin axonal markers, that MDMA users are more sensitive to the negative cognitive effects of sleep deprivation than matched controls, and that MDMA users have increased rates of sleep-disordered breathing than non-MDMA users. None of these findings would have been possible without the staff and facilities made available by the CISRE.

Altered pain responses in abstinent (±)3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) users.

     Studies conducted at the CISRE have demonstrated that sleep disruption leads to next-day reductions in diffuse noxious inhibitory controls (DNIC), a measure of central nervous system (CNS) pain inhibition, in both clinical populations (i.e., patients with temperomandibular joint syndrome) and non-clinical populations. Integration of CISRE and CRU has facilitated studies linking nocturnal sleep quantity and quality with state-of-the-art measurements of pain sensitivity during the daytime. Sleep studies conducted in daily cannabis users revealed that use of zolpidem during a 3-day period of acute abstinence led to significant improvements in sleep, and lessened the intensity of withdrawal symptoms. This observation has led to the suggestion that use of hypnotic medications may be useful in the treatment of cannabis use disorders. The findings also highlight the potential impact of nocturnal interventions on daytime function.

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