Dag Linnarsson

Cardiovascular responses to upright and supine exercise in humans after 6 weeks of head-down tilt (-6 degrees).

Abstract Seven healthy men performed steady-state dynamic leg exercise at 50u2009W in supine and upright postures, before (control) and repeatedly after 42u2009days of strict head-down tilt (HDT) (−6°) bedrest. Steady-state heart rate (fc), mean arterial blood pressure, cardiac output (Q˙c), and stroke volume (SV) were recorded. The following data changed significantly from control values. The fc was elevated in both postures at least until 12u2009days, but not at 32u2009days after bedrest. Immediately after HDT, SV and Q˙c were decreased by 25u2009(SEMu20093)% and 19u2009(SEMu20093)% in supine, and by 33u2009(SEMu20095)% and 20u2009(SEMu20093)% in upright postures, respectively. Within 2u2009days there was a partial recovery of SV in the upright but not in the supine posture. The SV and Q˙c during supine exercise remained significantly decreased for at least a month. Submaximal oxygen uptake did not change after HDT. We concluded that the cardiovascular response to exercise after prolonged bedrest was impaired for so long that it suggested that structural cardiac changes had developed during the HDT period.

Short-arm centrifugation as a partially effective musculoskeletal countermeasure during 5-day head-down tilt bed rest—results from the BRAG1 study

PurposeHuman centrifugation, also called artificial gravity (AG), is proposed as a combined strategy against detrimental effects of microgravity in long-term space missions. This study scrutinized human short-arm centrifugation as countermeasure against musculoskeletal de-conditioning.MethodEleven healthy male subjects [mean age of 34 (SD 7) years] completed the cross-over trial, including three campaigns of −6° head-down tilt bed rest (HDT) for 5xa0days, with preceding baseline data collection and recovery phases. Bed rest without AG was used as control condition (Ctrl), and AG with 1xa0g at the center of mass applied once per day for 30xa0min in one bout (AG1×30) and in 6 bouts of 5xa0min (AG6×5, 3-min rest between bouts) as experimental conditions. End-points were muscle strength, vertical jump performance, and biomarkers of bone and protein metabolism.ResultAG6×5 was better tolerated than AG1×30. Bone resorption markers CTX, NTX, and DPD all increased by approximately 25xa0% toward the end of bed rest (Pxa0<xa00.001), and nitrogen balance decreased by approximately 3xa0g/day (Pxa0<xa00.001), without any protection by AG (Pxa0>xa00.4). Decreases in vertical jump height by 2.1 (SE 0.6) cm after Ctrl bed rest was prevented by either of the AG protocols (Pxa0=xa00.039).ConclusionThe present study yielded succinct catabolic effects upon muscle and bone metabolism that were un-prevented by AG. The preservation of vertical jump performance by AG in this study is likely caused by central nervous rather than by peripheral musculoskeletal effects.

Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under bed rest conditions

CD200 is a transmembrane protein that belongs to the immunoglobulin family of proteins and is ubiquitously expressed on a variety of cell types. Upon interaction with its receptors (CD200Rs) expressed on myeloid-derived cells and T lymphocytes, an immunoregulatory signal is delivered to receptor-expressing cells. Previous studies have implicated a role for CD200:CD200R in the regulation of the expression of mRNA markers of osteoclastogenesis/osteoblastogenesis, following interaction of CD200 (on osteoblast precursors) with CD200R1 (on osteoclast precursors). Signaling of CD200R1 is hypothesized to attenuate osteoclastogenesis. We have investigated whether levels of soluble forms of CD200 and/or CD200R1 (sCD200, sCD200R1) are altered in volunteers undergoing 6° head down tilt bed rest to mimic conditions of microgravity known to be associated with preferential osteoclastogenesis and whether countermeasures, reported to be beneficial in attenuation of bone loss under microgravity conditions, would lead to altered sCD200 and sCD200R1 levels. Our data suggest that, as predicted, sCD200 levels fall under bed rest conditions while sCD200R1 levels rise. In subjects undergoing 30-minute per day continuous centrifugation protocols, as a countermeasure to attenuate changes which may lead to bone loss, these alterations in sCD200 and sCD200R1 levels seen under conditions of bed rest were abolished or attenuated. Our results suggest that measurement of sCD200 and/or sCD200R1 may prove a useful and rapid means of monitoring subjects at risk of bone loss and/or accessing the efficacy of treatment regimes designed to counter bone loss.