Impact of Daily Lower‐Body Negative Pressure or Cycling Followed by Venous Constrictive Thigh Cuffs on Bedrest‐Induced Orthostatic Intolerance

Figures

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  Figure 1. Overview of interventions in the SANS‐CM (Spaceflight‐Associated Neuro‐Ocular Syndrome Countermeasure) study, which enrolled 47 healthy participants to 30 days of bedrest. Subjects were assigned to 2×3 hours of daily lower‐body negative pressure (−25 mm Hg) per day (n=12) and 1 hour of cycling with 45% of maximal VO2, followed by wearing venous constrictive thigh cuffs for 6 hours 6 days per week (n=12). These strategies were compared with a positive control, who remained in an upright seated body position for 2×3 hours per day (n=11; positive control) and a negative control group without countermeasure (n=12). Orthostatic tolerance was computed as time to presyncope in 80° head‐up tilt‐table testing with incremental lower‐body negative pressure following 15 minutes of upright standing (International Standard Measure protocol). Tilt‐table testing was conducted in the morning hours following an overnight fast 5 days before and immediately after bedrest. Plasma volume was measured 2 days before and at day 28 of bedrest. Control indicates no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs on 6 days per week; LBNP, lower‐body…

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  Figure 2. Continuous FBP and HR before (upper row) and after bedrest (lower row) in a representative participant during combined head‐up tilt testing and LBNP. Time to presyncope decreased following bedrest. The participant also showed markedly increased HR while supine and during orthostatic testing following bedrest. bpm indicates beats per minute; FBP, finger blood pressure; HR, heart rate; and LBNP, lower‐body negative pressure.

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  Figure 3. Kaplan–Meier survival analyses on time to presyncope, which was computed to compare orthostatic tolerance, before and after in each group. The lower panel shows individual data on orthostatic tolerance before and after bedrest for each intervention group (P values for linear mixed‐effects analysis). Control indicates no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs on 6 days per week; LBNP, lower‐body negative pressure for 6 hours per day; seated, upright seated body position for 6 hours per day; and time to presyncope (ttPS),.

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  Figure 4. Individual values including mean±SD of systolic and diastolic blood pressure before and after bedrest in supine and standing position including adjusted P values. Upper‐arm blood pressure was measured every 2 minutes, resulting in up to 3 measurements at baseline and in the first 5 minutes of standing after an initial hemodynamic stabilization of ≈1 minute. Control indicates no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs 6 days per week; LBNP, lower‐body negative pressure for 6 hours per day; and seated, upright seated body position for 6 hours per day.

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  Figure 5. Individual values including mean±SD of heart rate before and after bedrest in supine and standing position as well as adjusted P values. Data were obtained of continuous heart rate recordings via ECG. Data collection of 5 minutes was strived, but respecting hemodynamic instability while standing following bedrest, a minimum of 60 seconds of stable signals were included in the analysis. bpm indicates beats per minute; control, no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs 6 days per week; LBNP, lower‐body negative pressure for 6 hours per day; and seated, upright seated body position for 6 hours per day.

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  Figure 6. Individual values including mean±SD and adjusted P‐values of plasma volume, which was measured by CO‐rebreathing before and at the end of bedrest. We observed a reduction of plasma volume following immobilization in all participants, except in the cycling group. Control indicates no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs 6 days per week; LBNP, lower‐body negative pressure for 6 hours per day; seated, upright seated body position for 6 hours per day.

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  Figure 7. Correlation of changes in plasma volume following bedrest (x axis) with differences in time to presyncope (y axis) before and after bedrest in a pooled correlation analysis. Both values were compared by a Spearman regression as changes in plasma volume did not meet criteria for normal distribution in Shapiro–Wilk test (W=0.8848, P=0.0003). In contrast to previous assumptions, maintenance of plasma volume during bedrest did not lead to preserved orthostatic tolerance. Control indicates no countermeasure; cycling, 1 hour of cycling followed by 6 hours of wearing venous constrictive thigh cuffs 6 days per week; LBNP, lower‐body negative pressure for 6 hours per day; and seated, upright seated body position for 6 hours per day.