The Russians currently use Braslet—an elastic thigh band—to help sequester blood in the legs and alleviate symptoms resulting from cephalad fluid shifts. While promising, this device has not been tested as a SANS countermeasure. Lower body negative pressure (LBNP) is an alternative approach, which draws fluid into the legs using vacuum mechanism. Both have drawbacks, however. Braslet devices are custom-built, difficult to obtain, and have limited calibration options. LBNP is typically bulky and hence could only be used at limited times. As an alternative to Braslet, we tested the Kaatsu thigh cuff system. This commercially available system is designed for enhanced muscle training on Earth. In addition, we investigated use of a LymphaPress compression garment configured to provide a vascular resistance for fluid return from the lower body (as opposed to enhanced fluid return for which the device was designed for clinically). In Experiments 1 and 2 we conducted tests using both countermeasures (at different inflation pressures) in healthy subjects undergoing -6 degrees head-down tilt (HDT). We characterized cerebral blood volume and flow, intraocular pressure, structural eye parameters, and cerebral vascular parameter changes associated with application, maintenance, and following release of each countermeasure. In Experiment 3, we tested the Kaatsu system in neurointensive care unit patients with invasive ICP devices implanted to monitor and treat elevated ICP.

Together, the data from these studies suggested that—at the chosen inflation pressures--neither countermeasure exhibited significant potential as a treatment for, or mitigator of, cephalad fluid shifts and elevated ICP.

Results include: (1) an assessment of both thigh cuffs and a compression garment as a SANS countermeasure, (2) assessment of the influence of these devices on cerebrovascular and ocular parameters, (3) parameterization of countermeasure deployment and rebound effects on multiple physiological variables, and (4) information regarding optimized deployment of the countermeasures.

Earth Benefits: Currently, there are few treatment methods for elevated ICP, which affects patients with traumatic brain injury, stroke, hydrocephalus, and cancer patients. None of the current methods involve non-invasive mechanical devices—instead focusing on surgical procedures or medications. This work therefore has the potential to identify one or more countermeasures and/or protocols—within a novel class of countermeasures—that could be used to help manage intracranial fluids and pressure. Since these approaches do not require drugs, they avoid the potential side effects, drug-drug interactions, or longer-lasting effects that often come from medication use.

In year 2 of the project we initiated and completed three human experiments. In Experiment 1, we tested n=18 healthy subjects during a -6 degree head-down tilt protocol. Subjects were monitored during two 3-hour sessions (one for each countermeasure, randomized order) consisting of 20-min periods in each of the following orientations, in sequence: +50 degree HUT (head up tilt), supine, -6 degree HDT, -6 degree HDT during countermeasure deployment, -6 degree HDT post-deployment of the countermeasure, supine, and briefly again at 50 degree HUT. All subjects were tested with Kaatsu at 180 SKU deployment pressure and Lymphapress at 34-36 mmHg pressures, in counterbalanced orders. Experiment 2 tested n=12 healthy subjects identically as in Experiment 1, however, with higher countermeasure pressures: Kaatsu at a deployment pressure of 300 SKU and Lymphapress at pressures of 43-45 mmHg. In Experiment 3, the Kaatsu system was tested in n=5 patients in the NeuroICU in collaboration with Dr. Eric Bershad with invasive ICP monitoring for 20 min baseline, 20 min Kaatsu deployment, and 20 min post-deployment at 250 SKU. Neither of the investigated mechanical countermeasure devices caused adverse effects in subjects and were well tolerated throughout trials. Kattsu cuffs were deemed less obtrusive and more practical to deploy due to their small size and compliance. The Lymphapress system was overall less practical to deploy due to its size and mode of application that required subjects to wear large inflatable compression pants—sufficiently so to preclude their use in NeuroICU patients with unstable ICP in Experiment 3.

Experiments 1 and 2 demonstrated significant sequestration of blood in the legs during Kaatsu deployment, whereas Lymphapress deployment did not. No significant changes in cerebral or ocular parameters (cerebral blood volume, cerebral blood flow velocity, intraocular pressure) were observed during or following either countermeasure. We believe the negative findings were in part due to distinct design issues associated with each commercial device.

The Russians currently use Braslet, an elastic thigh band, to help sequester blood in the legs and alleviate symptoms resulting from cephalad fluid shifts. While promising, this device has not been tested as a VIIP countermeasure. Lower body negative pressure (LBNP) is an alternative approach, which draws fluid into the legs using vacuum mechanism. Both have drawbacks, however. Braslet devices are custom-built, difficult to obtain and have limited calibration options. LBNP is bulky and hence only one such device would be available in-flight at a time, limiting the number of astronauts who could use it, or the duration of use, each day. As an alternative to Braslet, we will test the Kaatsu thigh cuff system. This commercially available system is designed for enhanced muscle training on Earth. Instead of the LBNP alternative, we will investigate use of a LymphaPress compression garment configured to provide a vascular resistance for fluid return (as opposed to enhanced fluid return) from the lower body. In Experiment 1, we will conduct tests using both potential countermeasures in healthy subjects undergoing head-down tilt (HDT) to elevate ICP by +10 mmHg, and in neurointensive care unit (NeuroICU) patients with invasive ICP devices implanted to monitor and treat elevated ICP. We will establish the ICP, cerebral blood flow, intraocular pressure, structural eye parameters, and cerebral vascular parameter changes associated with application, maintenance, and release of each countermeasure. This will also enable calibration of our non-invasive versus invasive cerebral measurements. In Experiment 2, we will examine more gradual discontinuation of device use versus more abrupt discontinuation. In Experiment 3, we will seek to quantify the relationship between exposure time to the countermeasure and cerebral responses during exposure as well as post-release.

Together, these studies will help identify whether either countermeasure is a promising treatment for, or mitigator of, cephalad fluid shifts and elevated ICP. This project will increase the technology readiness level of mechanical countermeasures for VIIP from Countermeasure Readiness Level (CRL) 4 to CRL 6-7.

Earth Benefits: Currently, there are few treatment methods for elevated intracranial pressure, which affects patients with traumatic brain injury, stroke, hydrocephalus, and cancer patients. None of the current methods involve non-invasive mechanical devices—instead focusing on surgical procedures or medications. This work therefore has the potential to identify one or more countermeasures and/or protocols--within a novel class of countermeasures--that could be used to help manage intracranial fluids. Since these approaches do not require drugs, they avoid the potential side effects, drug-drug interactions, or longer-lasting effects that often come from medication use.

In year 1 of the project we: (1) obtained the commercial devices and learned in detail how they function, (2) adapted either the physical device or (when possible) normal-use protocols for our target ICP-related application, (3) conducted pilot studies to fine-tune suitable protocols for deployment, (4) worked closely with the clinical teams at both MGH (Massachusetts General Hospital) and Baylor College of Medicine to work out deployment requirements in clinical settings, and (5) finalized the device deployment protocols. Instead of using a standard Kaatsu protocol on the legs, which involves restriction of arterial inflow to the extremeties, we will use a lower pressure to restrict only venous outflow. Instead of the standard LymphaPress configuration of compressing fluids from the lower body to the abdomen, we will compress the abdomen area only to increase vascular resistance, enhance distal vascular dilation, and generate fluid sequestration in the lower body. Having completed device training, initial adaptation, protocol development phase, and pilot studies, we are about to initiate subject recruitment for the primary studies.

The Russians currently use Braslet, an elastic thigh band, to help sequester blood in the legs and alleviate symptoms resulting from cephalad fluid shifts. While promising, this device has not been tested as a VIIP countermeasure. Lower body negative pressure (LBNP) is an alternative approach, which draws fluid into the legs using vacuum mechanism. Both have drawbacks, however. Braslet devices are only made in Russia and have limited calibration options. LBNP is bulky and hence only one such device would be available in-flight at a time, limiting the number of astronauts who could use it, or the duration of use, each day. In place of the Braslet, we will test the Kaatsu thigh cuff system, which is used for enhanced muscle training on Earth. Instead of the LBNP alternative, we will investigate use of a LymphaPress compression garment configured to progressively compress fluids from the lower ribcage towards the knee. In Experiment 1, we will conduct tests using both potential countermeasures in healthy subjects undergoing head-down tilt (HDT) to elevate ICP by +10 mmHg, and in neurointensive care unit (NeuroICU) patients with invasive ICP devices implanted to monitor and treat elevated ICP. We will establish the ICP, cerebral blood flow, intraocular pressure, structural eye parameters, and cerebral vascular parameter changes associated with application and release of each countermeasure. This will also involve calibration of our non-invasive versus invasive cerebral measurements. In Experiment 2, we will determine if gradual discontinuation of device use may be safer than abrupt discontinuation. In Experiment 3, we will seek to quantify the relationship between exposure time to the countermeasure and cerebral responses during exposure as well as post-release.

Together, these studies will help identify which countermeasure is the most promising treatment for, or mitigator of, cephalad fluid shifts and elevated ICP. This project will increase the technology readiness level of mechanical countermeasures for VIIP from Countermeasure Readiness Level (CRL) 4 to CRL 7.