Role for Lower Extremity Interstitial Fluid Volume Changes in the Development of Orthostasis after Simulated Microgravity
Reentry orthostasis after exposure to the conditions of spaceflight is a persistent problem among astronauts. In a previous study, a computer model systems analysis was used to examine the physiologic mechanisms involved in this phenomenon. In this analysis, it was determined that an augmented capacitance of lower extremity veins due to a fluid volume contracture of the surrounding interstitial spaces during spaceflight results in an increase in sequestered blood volume upon standing and appears to be the initiating mechanism responsible for reentry orthostasis. In this study, we attempt to validate the central premise of this hypothesis using a ground-based spaceflight analog. 10 healthy subjects were placed at bed rest in a 6 head down tilt position for 60 days of bed rest. The impact of adaptations in interstitial fluid volume and venous capacitance in the lower extremities were then observed during a standard tilt test protocol performed before and after the confinement period. The interstitial thickness superficial to the calcaneous immediately below the lateral malleolus was measured using ultrasound with a 17-5 MHz linear array transducer. Measurements of the changes in anterior tibial vein diameter during tilt were obtained by similar methods. The measurements were taken while the subjects were supine and then during upright tilt (80') for thirty minutes, or until the subject had signs of presyncope. Additional measurements of the superficial left tibia interstitial thickness and stroke volume by standard echocardiographic methods were also recorded. In addition, calf compliance was measured over a pressure range of 10-60 mmHg, using plethysmography, in a subset of these subjects (n = 5). There was a average of 6% diminution in the size of the lower extremity interstitial space as compared to measurements acquired prior to bed rest. This contracture of the interstitial space coincided with a subsequent relative increase in the percentage change in tibial vein diameter and stroke volume upon tilting in contrast to the observations made before bed rest (54 vs 23% respectively). Compliance in the calf increased by an average of 36% by day 27 of bedrest. A systems analysis using a computer model of cardiovascular physiology suggests that microgravity induced interstitial volume depletion results in an accentuation of venous blood volume sequestration and is the initiating event in reentry orthostasis. This hypothesis was tested in volunteer subjects using a ground-based spaceflight analog model that simulated the body fluid redistribution induced by microgravity exposure. Measurements of changes in the interstitial spaces and observed responses of the anterior tibial vein with tilt, together with the increase in calf compliance, were consistent with our proposed mechanism for the initiation of postflight orthostasis often seen in astronauts.