Aarts, Hugo M.

Background Hypoxia increases susceptibility to syncope during orthostatic stress. Furthermore, cardiac baroreflex sensitivity (cBRS) is attenuated during lower body negative pressure (LBNP). Recent studies suggest that there is cross‐talk between baroreceptors and carotid body chemoreceptors. With this in mind, hypoxia may further blunt cardiac baroreflex sensitivity (cBRS) during central hypovolemia in individuals susceptible to hypoxic syncope. Therefore, we hypothesized that participants susceptible to hypoxic syncope (“fainters”) during progressive central hypovolemia would have lower spontaneous cBRS during LBNP when compared to “nonfainters”. Methods Ten healthy male participants (35 ± 3 yr, BMI 25 ± 1 kg/m 2 ) were exposed to stepwise lower body negative pressure (LBNP, 5 minutes at 0, −15, −30, −45 mmHg) during both normoxia and hypoxia (FiO 2 = 0.12 – 0.15; S p O 2 ~85%). LBNP protocols were terminated early if participants developed presyncopal symptoms. Data from uncompleted stages were excluded. Heart rate (HR, 3 lead electrocardiogram) and mean arterial blood pressure (MAP, brachial arterial catheter) were continuously recorded. Spectral cBRS was calculated from the heart rate and blood pressure signals. Following experimentation, participants were stratified as fainters (developed presyncopal symptoms during hypoxic conditions, n=7) and nonfainters (n=3). Results MAP was lower in fainters than in nonfainters during hypoxia (interaction with LBNP p<0.05) while HR (p=0.38) and cBRS (p=0.43) were similar – . Hypoxia had a main effect vs normoxia on MAP, HR and cBRS in fainters (all p<0.02). In nonfainters hypoxia had a main effect vs normoxia on HR and cBRS (all p<0.03) and an interaction effect with LBNP on MAP (p<0.01). Conclusion Spontaneous cardiac baroreflex sensitivity is not attenuated in participants susceptible to hypoxic syncope during lower body negative pressure. This suggests that spontaneous cardiac baroreflex sensitivity does not contribute to orthostatic intolerance during hypoxia. Support or Funding Information Funding: W81XWH‐13‐2‐0038 Physiological response in fainters and nonfainters to LBNP during hypoxia and normoxia MAP, mmHg HR, beats·min −1 cBRS, ms·mmHg −1 Nonfainters Fainters Nonfainters Fainters Nonfainters Fainters Baseline Normoxia 104 ± 5 102 ± 3 62 ± 5 61 ± 3 13 ± 3 19 ± 2 Hypoxia 106 ± 6 97 ± 4 80 ± 6 72 ± 4 9 ± 3 11 ± 2 LBNP −15 mmHg Normoxia 109 ± 5 103 ± 3 68 ± 5 64 ± 3 11 ± 3 14 ± 2 Hypoxia 106 ± 6 90 ± 4 88 ± 6 72 ± 4 9 ± 3 14 ± 2 LBNP −30 mmHg Normoxia 107 ± 5 98 ± 3 79 ± 5 74 ± 3 8 ± 3 11 ± 2 Hypoxia 103 ± 6 82 ± 5 95 ± 6 79 ± 5 8 ± 3 9 ± 3 LBNP −45 mmHg Normoxia 101 ± 5 99 ± 3 92 ± 5 84 ± 4 6 ± 2 5 ± 2 Hypoxia 89 ± 6 N/A 113 ± 6 N/A 3 ± 3 N/A Different vs. nonfainters p<0.05 Different vs. normoxia p<0.05

The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (V̇o2max) and to explore sources of variation therein. Since 1949, 80 studies with a total of 949 participants (>90% men) have been published with data on strict bed rest and V̇o2max. The studies were conducted mainly in young participants [median age (interquartile range) 24.5 (22.4–34.0) yr]. The duration of bed rest ranged from 1 to 90 days. V̇o2max declined linearly across bed rest duration. No statistical difference in the decline among studies reporting V̇o2max as l/min (−0.3% per day) compared with studies reporting V̇o2max normalized to body weight (ml·kg−1·min−1; −0.43% per day) was observed. Although both total body weight and lean body mass declined in response to bed rest, we did not see any associations with the decline in V̇o2max. However, 15–26% of the variation in the decline in V̇o2max was explained by the pre-bed-rest V̇o2max levels, independent of the duration of bed rest (i.e., higher pre-bed-rest V̇o2max levels were associated with larger declines in V̇o2max). Furthermore, the systematic review revealed a gap in the knowledge about the cardiovascular response to extreme physical inactivity, particularly in older subjects and women of any age group. In addition to its relevance to spaceflight, this lack of data has significant translational implications because younger women sometimes undergo prolonged periods of bed rest associated with the complications of pregnancy and the incidence of hospitalization including prolonged periods of bed rest increases with age. NEW & NOTEWORTHY Large interindividual responses of maximal oxygen uptake (V̇o2max) to aerobic exercise training exist. However, less is known about the variability in the response of V̇o2max to prolonged bed rest. This systematic review and meta-analysis showed that pre-bed-rest V̇o2max values were inversely associated with the change in V̇o2max independent of the duration of bed rest. Moreover, we identified a large knowledge gap about the causes of decline in V̇o2max, particularly in postmenopausal women, which may have clinical implications.