Newhouse, Lauren P.

Background Patients with sleep apnea experience repeated, intermittent hypoxic exposures during sleep and are at increased risk of developing hypertension. The mechanisms that contribute to high blood pressure in these patients are not completely understood. In this context, we sought to examine the effect of intermittent hypoxic exposures on baroreflex sensitivity and blood pressure. We hypothesized 3‐hours of intermittent hypoxia would result in a decrease in baroreflex sensitivity in healthy adults. We further hypothesized any decrease baroreflex sensitivity would be related to an increase in blood pressure following intermittent hypoxia. Methods Six (5M/1F) young healthy, non‐obese, subjects without sleep apnea completed 3‐hours of intermittent hypoxia. Intermittent hypoxia consisted of 25‐second exposures to hypoxic gas (0.05 F i O 2 ) separated by 2 minutes of room air breathing, resulting in 25‐hypoxic events per hour in which oxygen saturation (S p O 2 ) was significantly reduced (Normoxia: 97%, Hypoxia: 89%, p<0.01). Beat‐to‐beat heart rate (electrocardiogram) and blood pressure (finger photoplethysmography) were measured continuously. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method (WinCPRS) and data are reported from 10‐minutes of quiet, normoxic rest before and after the intermittent hypoxia protocol. Results We observed a significant reduction in spontaneous cardiac baroreflex sensitivity to falling pressures (“down‐down”) following intermittent hypoxia (Control=22±2, IH=15±2 ms/mmHg; p=0.02). No change in baroreflex sensitivity to rising pressures (“up‐up”) was observed (Control=25±2, IH=20±6 ms/mmHg; p=0.41). A relationship between baroreflex sensitivity and mean arterial blood pressure was observed, such that a reduction in baroreflex sensitivity tended to be related to an increase in blood pressure (“down‐down”: R=−0.45, p=0.14; “up‐up”: R=−0.54, p=0.07). Conclusions Intermittent hypoxia results in a decrease in baroreflex sensitivity, which is related to an increase in blood pressure. These data may have important implications for mechanisms contributing to the risk of hypertension in individuals with sleep apnea. Support or Funding Information DK90541 (MJJ), HL120570 (JKL)

Background Individuals with sleep apnea experience repeated intermittent hypoxic exposures during sleep. Previous work in sleep apnea showed patients have an increased heart rate (HR), corrected QT interval (QTc), QTc dispersion and P‐wave maximum duration and dispersion (max‐min P‐wave duration). Such changes have been linked to increased risk of cardiovascular disease and sudden cardiac death. Unfortunately, the mechanisms contributing to these changes are not completely understood. Given that individuals with sleep apnea experience repeated intermittent hypoxic exposures during sleep, we tested the hypothesis that exposure to intermittent hypoxia (IH) in young healthy adults would result in similar ECG changes to those seen in patients with sleep apnea. Methods To test this hypothesis, we completed ECG analysis of 7 healthy humans (6M/1F, Age=29±5 years, BMI=24±4kg/m 2 ) without sleep apnea before and after 3‐hours of exposure to IH. Subjects were exposed to hypoxic gas (0.05 FiO2) for 25‐seconds separated by 2‐minutes of room air breathing. This resulted in 25 hypoxic events per hour in which oxygen saturation was significantly reduced (Normoxia: 97%, Hypoxia: 89%, p<0.01). ECG analysis was completed in Lab Chart 7 software and consisted of measurement of intervals (RR, PR, QT), durations (P, QRS), and amplitudes (P, Q, R, S, T) during 10 minutes of normoxic quiet rest before and after IH exposure. QTc was calculated using Bazett's formula (QT duration/√HR). Dispersion of QTc and P waves were calculated as max duration ‐min duration. Results HR was significantly increased following IH (60±8 vs. 66±8 beats/min, baseline vs. post‐IH, respectively, p<0.05). There was no significant change in P‐wave maximum duration or dispersion following IH. QT interval was significantly decreased and QTc was significantly increased following IH (QT interval: 377±13 vs. 368±8ms, QTc: 377±22 vs 384±22ms, baseline vs. post‐IH, p<0.05 for both). QTc dispersion was not significantly different from baseline following IH. Conclusions We found that 3 hours of experimentally‐induced IH in young healthy individuals resulted in increased HR, decreased QT interval, and increased QTc. These data suggest that IH exposure experienced by patients with sleep apnea may contribute to ECG changes commonly observed in this population and subsequent increases in cardiovascular morbidity and mortality. Support or Funding Information Funding : DK90541 (MJJ), HL120570 (JKL)

Background We have previously shown that the carotid body chemoreceptors play an important role in glucoregulation. When the carotid bodies are experimentally desensitized in humans, counterregulatory responses to hypoglycemia are attenuated. Whether carotid body activation conversely increases circulating glucose levels was previously unexamined. We hypothesize plasma glucose levels would be increased in young healthy adults after carotid body activation via acute intermittent hypoxia. Methods Seven (6M/1F, 21–34 years) healthy, non‐obese, non‐diabetic, subjects without sleep apnea completed 2 visits randomized to 3‐hours of intermittent hypoxia or continuous normoxia. Oxygen saturation and ventilation (turbine ventilation flow transducer) were measured continuously. Plasma glucose levels and carotid body chemosensitivity (hypoxic ventilatory response, HVR) were measured before and after the 3‐hour protocol. Intermittent hypoxia consisted of 25‐s exposures to hypoxic gas (0.05 FiO 2 ) separated by 2‐min of room air breathing, resulting in 25‐events per hour in which oxygen saturation was significantly reduced (Normoxia: 97%, Hypoxia: 89%, p<0.01). Results No changes in plasma glucose (93 vs 93 mg/dL, p=0.92) or HVR (−0.35 vs. −0.39 L/min/%SpO 2, p=0.56) were observed after 3‐hours of continuous normoxia. In contrast, circulating glucose levels and chemosensitivity increased after intermittent hypoxia when compared to baseline (92 vs 97 mg/dL, p<0.01) and (−0.39 vs −0.60 L/min/%SpO 2 , p=0.04), respectively. Additionally, the rise in glucose was significantly correlated with the rise in carotid body chemosensitivity (R=0.38, p=0.05). Conclusion Circulating glucose levels increased after 3‐hours of intermittent hypoxia. The significant relationship between HVR and circulating glucose suggests that the carotid bodies may play a role in altered glucose handling. These findings may have important implications for the high prevalence of diabetes in patients with sleep apnea. Support or Funding Information DK90541, HL120570