Browsing by Subject "obstructive sleep apnea"
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Item Mechanisms of Chemoreflex Control of Muscle Sympathetic Nerve Activity and Blood Pressure in Humans(2004-05-01) Hardisty, Janelle M.; Smith, Michael; Shi, Xiangrong; Clark, MichaelHardisty, Janelle M., Mechanisms of Chemoreflex Control of Muscle Sympathetic Nerve Activity and Blood Pressure in Humans. Doctor of Philosophy (Integrative Physiology), May 2004. The mechanisms linking obstructive sleep apnea (OSA) and cardiovascular disease are not fully understood; however, studies report patients with OSA exhibit chronic elevations in muscle sympathetic nerve activity (MSNA). This appears to be due to altered chemoreflex control of MSNA, mediated primarily by hypoxia. Yet, a correlation between degree of hypoxia and chemoreflex control of MSNA is unknown. Therefore, it was evaluated whether degree of hypoxia occurring during apnea determines the sympathoexcitatory and blood pressure responses, and whether these responses are augmented in OSA patients. Additionally, it was studied whether altered chemoreflex function in OSA patients is predictive of blood pressure response to apnea. In a clinical setting, the blood pressure response to voluntary apnea was determined to evaluate whether this could be used as a non-invasive measure of chemoreflex gain in OSA. Finally, the effect of hyperoxia on MSNA was studied to determine whether 15 min of hyperoxia, following intermittent hypoxic apnea, reverses the elevation of MSNA and altered chemoreflex control of MSNA. Consistent with the hypotheses, a relationship between MSNA responses, blood pressure response and level of hypoxia were determined. MSNA and peak systolic pressure responses were augmented in OSA subjects (p≤0.05 and p≤0.05, respectively), as well as, chemoreflex gain (p≤0.05). Clinically, peak systolic pressure responses to apnea were augmented in OSA patients (p˂0.001). Finally, basal MSNA and chemoreflex control of MSNA, following hyperoxia, was not different from baseline through 180 min of recovery (p=0.940 and p=0.278, respectively). These data support the hypotheses that chemoreflex gain is predicative of the blood pressure response; and furthermore, the MSNA and blood pressure responses to hypoxic apnea are augmented in OSA. Additionally, peak systolic pressure responses to voluntary apnea are augmented in OSA. Additionally, peak systolic pressure responses to voluntary apnea are augmented in OSA patients and could possibly be used as a marker of chemoreflex gain. Moreover, these data support the hypothesis that hyperoxia can reverse basal sympathoexcitation and augmented chemoreflex control of MSNA, associated with hypoxic apnea, supporting that elevations in MSNA are hypoxia mediated.Item Role of Arousal Threshold in Sleep Health Disparities and Outcomes Among Pediatric Patients with Obstructive Sleep Apnea(2022-05) Gracia, Fernando I.; Rickards, Caroline A.; Jones, Harlan P.; Basha, Riyaz; Cunningham, J. ThomasBlack/African American (Black) children are at increased risk of experiencing continued obstructive sleep apnea (OSA) disease following adenotonsillectomy (A&T), which is the first-line treatment for OSA in children. The nadir epiglottic pressure preceding arousal, known as the arousal threshold (ArTH), and allostatic load (AL), a measure of the impact of environmental stress on the body, are both associated with the severity and incidence of the disease. However, the contribution of these factors to the sleep health disparities among Black pediatric patients is unknown. Therefore, our overall objective of this study was to determine the role of arousal threshold and allostatic load in sleep health disparities amongst treatment outcomes in pediatric patients with OSA. The current study leveraged archival data from the Childhood Adenotonsillectomy Trial (CHAT). 464 children aged 5 to 9 years with obstructive sleep apnea were randomized to receive either early adenotonsillectomy or watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were examined at baseline and after seven months. Our sample included 183 participants who had the required allostatic load baseline data for the analysis and a sub-sample of 98 participants who underwent adenotonsillectomy surgery and had follow-up data. We examined AL index among Black and White children to identify differences and create a model that could explain the noted sleep disparities in response to adenotonsillectomy surgery. To achieve the overall objective and test the first hypothesis that Black children will have increased arousal threshold and allostatic load compared to their White counterparts, univariate ANCOVAs were conducted to determine potential differences between Black and White children for ArTH and AL adjusted for demographic and socioeconomic factors. To test the second hypothesis that increased arousal threshold and allostatic load will predict higher adenotonsillectomy failure rates. Quadratic discriminant function analysis was used to determine if ArTH and AL load predicts adenotonsillectomy failure. A&T failure is defined as a participant having an obstructive apnea index (OAI) ≥ 1 and an apnea-hypopnea index (AHI) ≥ 2 at follow-up 7 months after A&T. Key findings were an increased allostatic load in Black children (P=0.09) and an interaction effect between race and premature birth. Black Children born premature had a higher allostatic load than White children born premature (P=0.09). Additionally, among the subsample of participants who underwent adenotonsillectomy surgery, a difference between Black and White race was found for ArTH (p < 0.05). For predicting the success and failure of adenotonsillectomy surgery, the test model showed a 54.8% success rate in predicting group membership. The findings from our study can be used to guide the development and testing of future sleep health interventions and further elucidate the etiology of sleep health disparitiesItem Role of ΔFosB in nucleus of the solitary tract (NTS) in cardiovascular adaptations to chronic intermittent hypoxia (CIH) in rats(2015-08-01) Wu, Qiong; Mifflin, Steve W.; Cunningham, J. Thomas; Schreihofer, Ann M.Chronic intermittent hypoxia (CIH) rodent model is widely utilized to study obstructive sleep apnea (OSA) associated disease such as hypertension. Arterial chemoreceptor is activated by CIH, and leads to increased sympathetic nerve discharge, resulting in elevated arterial pressure. The central neuronal mechanisms of CIH induced hypertension are barely understood. The nucleus of the solitary tract (NTS) receives the first synaptic inputs from arterial chemoreceptor afferents. Transcription factor ΔFosB is increased in the NTS after a 7 day-CIH exposure. We hypothesize that NTS ΔFosB could mediate neuronal plasticity, contribute to CIH induced hypertension. Three specific aims were addressed. Aim 1: To determine the relationship between NTS ΔFosB and CIH hypertension. Viral constructs were delivered into NTS to functionally block ΔFosB (ΔJunD group). Mean arterial pressure (MAP) was measured in day time when rats were exposed to intermittent hypoxia and night time when they were in normoxia. The increase in MAP observed in ΔJunD and sham groups during day time was dampened in ΔJunD group during night time, indicating the contribution of ΔFosB to the sustained component of CIH associated hypertension. Aim 2: To determine the time-course of induction of ΔFosB immunoreactive NTS neurons during CIH exposure. Rats were separated into normoxia, 1 day, 3, 5, 7 days CIH, and 1 day, 3, 7 days recovery after 7 days CIH groups. ΔFosB immunoreactivity increased within 1 day CIH, and maintained this elevation throughout 7 days of CIH. 1 day recovery was sufficient to reduce ΔFosB immunoreactivity to normoxia level. Therefore, ΔFosB under CIH develops rapidly. Aim 3: To determine the function of ΔFosB in glutamatergic transmission after CIH. Miniature excitatory post-synaptic current (mEPSC) properties of NTS neurons of rats exposed to either different days of CIH or room air were compared. CIH increased mEPSC amplitude but not frequency, suggesting a post-synaptic site of effect. Additionally, functional blockade of NTS ΔFosB with ΔJunD decreased mEPSC amplitude back to normoxia level. Finally, overexpression of NTS ΔFosB increased mEPSC amplitude to similar levels as CIH. These results suggest that ΔFosB in NTS neurons mediates molecular adaptations which might play an important role in CIH associated hypertension.Item THE EFFECT OF CONTINUOUS POSITIVE AIRWAY PRESSURE TREATMENT ON CARDIOVASCULAR REACTIVITY IN OBSTRUCTIVE SLEEP APNEA.(2014-03) Jouett, Noah; Smith, Michael L.; Sleep Consultants, IncObstructive sleep apnea (OSA) is a disorder in which patients intermittently stop breathing while sleeping. OSA has been associated with an increased risk for cardiovascular disease. This study investigates the role of the blood pressure (BP) response to voluntary breath-holding as an indicator of treatment success. We have found that OSA patients have elevated BP responses to voluntary breath-holding compared to people of a similar age and body weight. This study has found that with adequate treatment, this BP response is effectively attenuated. We propose a voluntary 20 second breath-hold as an effective and objective measure of treatment success in OSA. Purpose (a): To investigate whether or not well-treated obstructive sleep apnea (OSA) subjects will have a decreased Δ systolic blood pressure (SBP) response to voluntary apnea than untreated subjects. Methods (b): 21 OSA patients were stratified into treated (n=15) and untreated (n=6) groups based on their Treatment Success Index (TSI). The TSI takes into account a patient’s continuous positive airway pressure (CPAP) compliance and reduction in apnea-hypopnea index (AHI). Patients with TSIs of less than 85 (out of 100) were considered “untreated” while those over 85 were considered “treated.” This study took place at Sleep Consultants, Inc (Fort Worth, TX). Patients were instrumented with 3-lead ECG, pulse oximeter and a Finometer, which recorded beat-to-beat blood pressure. After respiring normally 3 times, the patient was asked to initiate a voluntary apnea for 20 seconds and the SBP response was recorded. An unpaired t-test was performed on group averages, where a p2values were calculated where indicated with ANOVAs to determine significance. Results (c): The untreated mean ∆ SBP was 24.04 ± 7.271 mm Hg and the treated mean was 12.23 ± 3.57 mm Hg, which was significantly different (p=0.00165). TSI and ∆SBP were inversely and significantly correlated (P= -0.69, p=0.00119). The different treatment groups did not desaturate differently (p>0.05), and greater desaturations did not produce greater ∆ SBP responses (R2=0.003, p> 0.05). Conclusions (d): The SBP response to voluntary breath-holds decreases with adequate CPAP treatment independently from SaO2. Therefore, the underlying increase in sympathetic nervous activity (SNA) that drives the ∆ SBP response is likely attenuated with adequate CPAP treatment. This study proves the utility of this maneuver in evaluating treatment efficacy (i.e. reduction in SNA reactivity) in OSA patients in a clinical setting.Item THE ROLE OF SLEEP APNEA INDUCED REACTIVE OXYGEN SPECIES IN SYMPATHOEXCITATION(2013-04-12) McKay, PilarPurpose: The obstructive sleep apnea (OSA) patient experiences multiple hypopneas and apneas, or intermittent hypoxia (IH) throughout the night. In healthy subjects, one 20s to 30s bout of IH has been reported to increase muscle sympathetic nervous activity (MSNA) for periods of 3hrs. Results from animal and human investigations indicate that apnea induced elevations in reactive oxygen species (ROS) are associated with increases in MSNA. Increases in sympathetic activity result in increases in the operating point of the arterial baroreflex's control of blood pressure. We hypothesized that the IH induced increase in ROS and sympathoexcitation would attenuate arterial baroreflex (ABR) control of stroke volume (SV). Methods: Healthy human subjects (n = 11, 5 female) underwent neck pressure/suction (NP/NS) to assess carotid baroreflex (CBR) function before and after intermittent hypoxia training with or without the antioxidant, N-acetyl cysteine (NAC). During NP/NS, mean arterial pressure and stroke volume were recorded non-invasively using a finometer. Following baseline measurements for hemodynamic variables and CBR function, subjects were asked to ingest a drink containing either NAC or a placebo. One hour after ingestion, hemodynamic variables and ABR function were measured, following which the subjects were intermittently hypoxia trained (IHT) using 20s of intermittently breathing nitrogen and breath holding resulting in IH. After that, measurements of SV were recorded during NP/NS (immediately 30 minutes and 1 hour post IHT). A two way repeated measures analysis of variance (ANOVA) was used to analyze differences between treatment groups across time. Results: Repeated measures (ANOVA) comparing stroke volume between treatment groups identified that there were no differences in SV over time (p = 0.332). There was no difference in CBR function (p = 0.891) between placebo and NAC conditions. Conclusions: These data suggest that there is no significant influence of IHT or ROS on the CBR control of stroke volume.