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Background: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and under the influence of thigh occlusion cuffs available as a countermeasure device (Braslet cuffs)., Methods: Nine International Space Station crewmember subjects (expeditions 16-20) were examined in 15 experiment sessions 101 ± 46 days after launch (mean ± SD; 33-185). Twenty-seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs (162 parameter states/session). Quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by investigators from the NASA Telescience Center in Houston, TX, and the Mission Control Center in Korolyov, Moscow region, Russia., Results: 14 of 81 conditions (27 parameters measured at baseline, Valsalva, and Mueller maneuver) were significantly different when the Braslet was applied. Seven of 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression., Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient at the "microgravity bedside."