Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in 1) SNA discharge and 2) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mmHg, all P < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mmHg, all P > 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. NEW & NOTEWORTHY This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients.

New Findings: What is the central question of this study? This study evaluated the following central question: does N‐acetylcysteine (N‐AC), an antioxidant that readily penetrates the blood–brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N‐AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N‐AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N‐acetylcysteine (N‐AC) attenuates hyperacute intermittent hypoxia‐induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty‐eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg⁻¹ of N‐AC (n = 16) or vehicle placebo (n = 12). Three‐lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole‐blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end‐expiratory apnoeas with 100% nitrogen. N‐AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N‐AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N‐AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

Central Sleep Apnea (CSA) is characterized by intermittent apneas and hypopneas during sleep that result from absent central respiratory drive. CSA occurs almost exclusively during non‐rapid‐eye‐movement (NREM) sleep due to enhanced neuronal ventilatory drive during REM sleep that makes central apneas highly unlikely to form. A 45‐year‐old obese African American female presented with co‐existing Obstructive Sleep Apnea (OSA) and CSA, not in the form of mixed or complex sleep apnea. Peculiarly, her CSA occurred only during rapid‐eye‐movement (REM) sleep, which is exceedingly rare. The patient9s CSA was resolved when appropriate positive airway pressure (PAP) was prescribed. Our patient remains stable and has reported significant benefit from PAP usage. We offer possible neuro‐physiological mechanisms herein, including enhanced loop gain and/or malfunction or malformation of the pre‐Botzinger nucleus or other neurological process, that could explain the unique findings of this case.

Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Background: Over 20 million people in the United States suffer from Obstructive Sleep Apnea (OSA). Compared to the general population, OSA patients are 2.6 times more likely to experience sudden cardiac death (SCD), and it is suspected that this is due, in part, to QT prolongation leading to fatal dysrhythmias. OSA events have previously been shown to cause prolonged QT intervals compared to the post-apnea hyperventilation period, and studies have also observed increased QT dispersion in patients without cardiac disease. However, those with cardiac disease may be at the greatest risk for SCD, and it is not known what role QT prolongation plays and what factors influence these responses. Thus, the purpose of this study is to evaluate the factors that affect QT interval during periods of sleep apnea including OSA severity, time of night, and quantity of obstructive apneic events during sleep. Methods: We determined QTc intervals from the electrocardiograms of 36 patients undergoing polysomnography for diagnosis of OSA. Patients that were selected had an apnea hypopnea index >20/Hr and had no prior myocardial infarction or heart failure. Each patient’s ECG during their sleep study was analyzed to assess QT interval throughout the night. Baseline QT intervals were compared to QT intervals during obstructive apneas during the first 2 hours of sleep (Early) and last 2 hours of sleep (Late). In addition, apneas >40 seconds were analyzed in 11 patients for changes in QTc as the apnea progressed. Statistical comparisons were made with paired t tests and a one-way ANOVA analysis with repeated measures. Results: Early analyses of data showed QTc intervals in Early and Late apneas were significantly prolonged compared to awake baseline (p=0.04 and p=0.006 respectively). For patients with apneas >40 seconds, significant differences in QTc interval were observed at increasing time points during the apnea compared to the QTc immediately preceding the apnea (p<0.001). Furthermore, patients with longer apneas tend to have longer baseline QTc (p=0.07). Conclusions: Sleep apneic events are associated with periods of mild QTc prolongation despite some cardiac cycle shortening. The prolongation tends to become enhanced later in the night, implying that there is a cumulative effect of numerous prior apneas. Furthermore, prolongation tends to increase as the apnea duration progresses. Early data analyses also suggest that baseline QTc tends to be longer in patients who have more severe/longer apneic events throughout the night. Future studies will focus on QTc changes in OSA patients with prior heart disease, as these are the patients at greatest risk for serious arrhythmias during the night.

Background: The sitting position for craniotomies, although often surgically advantageous, can impose serious risks to patient safety. Objective(s): To evaluate long-term post-operative follow up in patients undergoing craniotomies in the sitting position. Design: Retrospective cohort study. Setting: We utilized the TriNetX web interface to perform real-world data (RWD) analysis focusing on a long-term (10 year) follow-up of patients who underwent cranial anesthesia in sitting positions (CPT 00218). Patients: We performed two patients cohorts: cohort 1, patients aged > 50 years and cohort 2, patients with ages 18-50 Intervention: Patients with a history of Alzheimer’s, dementia, Parkinson’s, or any similar conditions were excluded. Main outcome measures: We evaluated embolism-related complications, postprocedural complications, vascular and circulatory complications, neurological conditions, hematomas and hemorrhages, and other pathologies including death. Risk ratio and other statistics were calculated in the TriNetX web-interface. Results: For the ten-year follow up period, we found that mortality (RR 3.663 (2.51-5.346); p< 0.0001) and delirium-all (RR 2.268 (1.106-4.652); p=0.021) were significantly higher in the older cohort (>50 years) than in the younger cohort (18-50 years). Irrespective of the type of surgical procedure, neurological complications do exist in the long term in patients undergoing craniotomies in sitting positions. Conclusions: Further analysis is needed to understand the root causes of the observed delirium phenomenon in the older patient population.