Christian M. Westby

Acute effects of hemodialysis on nitrite and nitrate: potential cardiovascular implications in dialysis patients.

Cardiovascular mortality in dialysis patients remains a serious problem. It is 10 to 20 times higher than in the general population. No molecular mechanism has been proven to explain this increased mortality, although nitric oxide (NO) has been implicated. The objective of our study was to determine the extent of the removal of the NO congeners nitrite and nitrate from plasma and saliva by hemodialysis, as this might disrupt physiological NO bioactivity and help explain the health disparity in dialysis patients. Blood and saliva were collected at baseline from patients on dialysis and blood was collected as it exited the dialysis unit. Blood and saliva were again collected after 4-5h of dialysis. In the 27 patients on dialysis, baseline plasma nitrite and nitrate by HPLC were 0.21±0.03 and 67.25±14.68 μM, respectively. Blood immediately upon exit from the dialysis unit had 57% less nitrite (0.09±0.03 μM; P=0.0008) and 84% less nitrate (11.04 μM; P=0.0003). After 4-5h of dialysis, new steady-state plasma levels of nitrite and nitrate were significantly lower than baseline, 0.09±0.01 μM (P=0.0002) and 16.72±2.27 μM (P=0.001), respectively. Dialysis also resulted in a significant reduction in salivary nitrite (232.58±75.65 to 25.77±10.88 μM; P=0.01) and nitrate (500.36±154.89 to 95.08±24.64 μM; P=0.01). Chronic and persistent depletion of plasma and salivary nitrite and nitrate probably reduces NO bioavailability and may explain in part the increased cardiovascular mortality in the dialysis patient.

Left ventricular remodeling during and after 60 days of sedentary head-down bed rest.

Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters,P< 0.001). Resting measures of LV volume and mass were ∼15% (P< 0.001) and ∼14% lower (P< 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values (P< 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.

Gradient compression garments protect against orthostatic intolerance during recovery from bed rest

IntroductionAbdomen-high, lower body graded compression garments (GCGs) may represent the next-generation of orthostatic intolerance protection with applications for exploration missions and commercial space flight.PurposeTo evaluate the efficacy of the GCG to prevent orthostatic intolerance after a 14-day 6° head-down tilt bed rest (BR) and to determine whether wearing thigh-high compression garments impairs recovery from BR.MethodsSixteen (12 M, 4 F) subjects participated in a 15-min 80° head-up tilt test 5xa0day before BR (BR-5), on the last morning of BR (BR+0), and on day 1 (BR+1) and 3 after BR (BR+3). No subjects wore the GCG on BR-5, and all subjects wore the GCG during testing on BR+0. Control subjects (nxa0=xa08) wore the GCG only through testing on BR+0. Treatment subjects (nxa0=xa08) wore the GCG on BR+0 and thigh-high garments on BR+1 and BR+2.ResultsNo subjects were presyncopal during tilt on BR+0 while wearing the GCG. Despite lower plasma volume index (BR-5: 1.52xa0±xa00.06, BR+0: 1.32xa0±xa00.05xa0l/m2), the tilt-induced increase in heart rate (ΔHR, 17xa0±xa02xa0bpm) and decrease in stroke volume (ΔSV, −28xa0±xa03xa0ml) on BR+0 were less than on BR-5 (24xa0±xa02xa0bpm, −43xa0±xa04xa0ml). On BR+1 ΔHR in the control group (33xa0±xa04xa0bpm) was higher than in the treatment group (23xa0±xa02xa0bpm) but there were no group differences on BR+3.ConclusionsWearing the GCG prevented the orthostatic intolerance that is normally present after BR. Thigh-high garments provided protection after BR, and wearing these garments did not impair recovery.

Internal jugular pressure increases during parabolic flight.

One hypothesized contributor to vision changes experienced by >75% of International Space Station astronauts is elevated intracranial pressure (ICP). While no definitive data yet exist, elevated ICP might be secondary to the microgravity‐induced cephalad fluid shift, resulting in venous congestion (overfilling and distension) and inhibition of cerebrospinal and lymphatic fluid drainage from the skull. The objective of this study was to measure internal jugular venous pressure (IJVP) during normo‐ and hypo‐gravity as an index of venous congestion. IJVP was measured noninvasively using compression sonography at rest during end‐expiration in 11 normal, healthy subjects (3 M, 8 F) during normal gravity (1G; supine) and weightlessness (0G; seated) produced by parabolic flight. IJVP also was measured in two subjects during parabolas approximating Lunar (1/6G) and Martian gravity (1/3G). Finally, IJVP was measured during increased intrathoracic pressure produced using controlled Valsalva maneuvers. IJVP was higher in 0G than 1G (23.9 ± 5.6 vs. 9.9 ± 5.1 mmHg, mean ± SD P < 0.001) in all subjects, and IJVP increased as gravity levels decreased in two subjects. Finally, IJVP was greater in 0G than 1G at all expiration pressures (P < 0.01). Taken together, these data suggest that IJVP is elevated during acute exposure to reduced gravity and may be elevated further by conditions that increase intrathoracic pressure, a strong modulator of central venous pressure and IJVP. However, whether elevated IJVP, and perhaps consequent venous congestion, observed during acute microgravity exposure contribute to vision changes during long‐duration spaceflight is yet to be determined.

NIRS-Derived Tissue Oxygen Saturation and Hydrogen Ion Concentration following Bed Rest: 2901

Reflectance Medical Inc., Westboro, MA Long-term bed rest (BR), a model of spaceflight, results in a decrease in aerobic capacity and altered submaximal exercise responses. The strongest BR-induced effects on exercise appear to be centrally-mediated, but longer BR durations may result in peripheral adaptations (e.g., decreased mitochondrial and capillary density) which are likely to influence exercise responses.

Custom Gradient Compression Stockings May Prevent Orthostatic Intolerance In Astronauts After Space Flight: 2897

Orthostatic intolerance after space flight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. NASA astronauts currently wear an inflatable anti-gravity suit (AGS) during re-entry, but this device is uncomfortable and loses effectiveness upon egress from the Shuttle. We recently determined that thigh-high, gradient compression stockings were comfortable and effective after space flight, though to a lesser degree than the AGS. We also recently showed that addition of splanchnic compression to this thigh-high compression stocking paradigm improved orthostatic tolerance to a level similar to the AGS, in a ground based model.