Blood pressure regulation V: in vivo mechanical properties of precapillary vessels as affected by long-term pressure loading and unloading

Recent studies are reviewed, concerning the in vivo wall stiffness of arteries and arterioles in healthy humans, and how these properties adapt to iterative increments or sustained reductions in local intravascular pressure. A novel technique was used, by which arterial and arteriolar stiffness was determined as changes in arterial diameter and flow, respectively, during graded increments in distending pressure in the blood vessels of an arm or a leg. Pressure-induced increases in diameter and flow were smaller in the lower leg than in the arm, indicating greater stiffness in the arteries/arterioles of the leg. A 5-week period of intermittent intravascular pressure elevations in one arm reduced pressure distension and pressure-induced flow in the brachial artery by about 50 %. Conversely, prolonged reduction of arterial/arteriolar pressure in the lower body by 5 weeks of sustained horizontal bedrest, induced threefold increases of the pressure-distension and pressure-flow responses in a tibial artery. Thus, the wall stiffness of arteries and arterioles are plastic properties that readily adapt to changes in the prevailing local intravascular pressure. The discussion concerns mechanisms underlying changes in local arterial/arteriolar stiffness as well as whether stiffness is altered by changes in myogenic tone and/or wall structure. As regards implications, regulation of local arterial/arteriolar stiffness may facilitate control of arterial pressure in erect posture and conditions of exaggerated intravascular pressure gradients. That increased intravascular pressure leads to increased arteriolar wall stiffness also supports the notion that local pressure loading may constitute a prime mover in the development of vascular changes in hypertension

Indices of Increased Decompression Stress Following Long-Term Bed Rest

Human extravehicular activity (EVA) is essential to space exploration and involves risk of decompression sickness (DCS). On Earth, the effect of microgravity on physiological systems is simulated in an experimental model where subjects are confined to a 6° head-down bed rest (HDBR). This model was used to investigate various resting and exercise regimen on the formation of venous gas emboli (VGE), an indicator of decompression stress, post-hyperbaric exposure. Eight healthy male subjects participating in a bed rest regimen also took part in this study, which incorporated five different hyperbaric exposure (HE) interventions made before, during and after the HDBR. Interventions i–iv were all made with the subjects lying in 6° HD position. They included (C1) resting control, (C2) knee-bend exercise immediately prior to HE, (T1) HE during the fifth week of the 35-day HDBR period, (C3) supine cycling exercise during the HE. In intervention (C4), subjects remained upright and ambulatory. The HE protocol followed the Royal Navy Table 11 with 100 min spent at 18 m (280 kPa), with decompression stops at 6 m for 5 min, and at 3 m for 15 min. Post-HE, regular precordial Doppler audio measurements were made to evaluate any VGE produced post-dive. VGE were graded according to the Kisman Masurel scale. The number of bubbles produced was low in comparison to previous studies using this profile [Kisman integrated severity score (KISS) ranging from 0–1], and may be because subjects were young, and lay supine during both the HE and the 2 h measurement period post-HE for interventions i–iv. However, the HE during the end of HDBR produced significantly higher maximum bubble grades and KISS score than the supine control conditions (p < 0.01). In contrast to the protective effect of pre-dive exercise on bubble production, a prolonged period of bed rest prior to a HE appears to promote the formation of post-decompression VGE. This is in contrast to the absence of DCS observed during EVA. Whether this is due to a difference between hypo- and hyperbaric decompression stress, or that the HDBR model is a not a good model for decompression sensitivity during microgravity conditions will have to be elucidated in future studies

Hypercapnia augments resistive exercise‐induced elevations in intraocular pressure in older individuals

The present study assessed the effect of 6° head down (establishing the cephalad displacement noted in astronauts in microgravity) prone (simulating the effect on the eye) tilt during rest and exercise (simulating exercise performed by astronauts to mitigate the sarcopenia induced by unloading of weight‐bearing limbs), in normocapnic and hypercapnic conditions (the latter simulating conditions on the International Space Station) on IOP.Volunteers (average age = 57.8 ± 6 yrs.; N = 10) participated in two experimental sessions, each comprising: i) 10‐min rest, ii) 3‐min handgrip dynamometry (30% max), and iii) 2‐min recovery, inspiring either room air (NCAP), or a hypercapnic mixture (1% CO2, HCAP). We measured IOP in the right eye, cardiac output (CO), stroke volume (SV), heart rate (HR) and mean arterial pressure (MAP) at regular intervals. Baseline IOP in the upright seated position while breathing room air was 14.1 ± 2.9 mmHg. Prone 6° HDT significantly (p < 0.01) elevated IOP in all three phases of the NCAP (rest: 27.9 ± 3.7 mmHg; exercise: 32.3 ± 4.9 mmHg; recovery: 29.1 ± 5.8 mmHg) and HCAP (rest: 27.3 ± 4.3 mmHg; exercise: 34.2 ± 6.0 mmHg; recovery: 29.1) trials, with hypercapnia augmenting the exercise‐induced elevation in IOP (p < 0.01). CO, SV, HR and MAP were significantly increased during handgrip dynamometry, but there was no effect of hypercapnia. The observed IOP measured during prone 6°HDT in all phases of the NCAP and HCAP trials exceeded the threshold pressure defining ocular hypertension. The exercise‐induced increase in IOP is exacerbated by hypercapnia

Substantial and Reproducible Individual Variability in Skeletal Muscle Outcomes in the Cross-Over Designed Planica Bed Rest Program

To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SD (Formula presented.) –SD (Formula presented.)), where SDExp and SDCon are the standard deviations of the change score (i.e., post – pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to −17% for knee extension torque, −2 to −12% for calf muscle area, and −1 to −8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65–0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between −0.5 and −0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations

Separate and Combined Effects of Hypoxia and Horizontal Bed Rest on Retinal Blood Vessel Diameters

Citation: Louwies T, Jaki Mekjavic P, Cox B, et al. Separate and combined effects of hypoxia and horizontal bed rest on retinal blood vessel diameters. Invest Ophthalmol Vis Sci. 2016;57:4927-4932. DOI:10.1167/ iovs.16-19968 PURPOSE. To assess the separate and combined effects of exposure to prolonged and sustained recumbency (bed rest) and hypoxia on retinal microcirculation. METHODS. Eleven healthy male subjects (mean 6 SD age ¼ 27 6 6 years; body mass index [BMI] ¼ 23.7 6 3.0 kg m À2 ) participated in a repeated-measures crossover design study comprising three 21-day interventions: normoxic bed rest (NBR; partial pressure of inspired O 2 , P i O 2 ¼ 133.1 6 0.3 mm Hg); hypoxic ambulation (HAMB; P i O 2 ¼ 90.0 6 0.4 mm Hg), and hypoxic bed rest (HBR; P i O 2 ¼ 90.0 6 0.4 mm Hg). Central retinal arteriolar (CRAE) and venular (CRVE) equivalents were measured at baseline and at regular intervals during each 21-day intervention. RESULTS. Normoxic bed rest caused a progressive reduction in CRAE, with the change in CRAE relative to baseline being highest on day 15 (DCRAE ¼ À7.5 lm; 95% confidence interval [CI]: À10.8 to À4.2; P &lt; 0.0001). Hypoxic ambulation resulted in a persistent 21-day increase in CRAE, reaching a maximum on day 4 (DCRAE ¼ 9.4 lm; 95% CI: 6.0-12.7; P &lt; 0.0001). During HBR, the increase in CRAE was highest on day 3 (DCRAE ¼ 4.5 lm; 95% CI: 1.2-7.8; P ¼ 0.007), but CRAE returned to baseline levels thereafter. Central retinal venular equivalent decreased during NBR and increased during HAMB and HBR. The reduction in CRVE during NBR was highest on day 1 (DCRVE ¼ À7.9 lm; 95 CI: À13.3 to À2.5), and the maximum DCRVE during HAMB (24.6 lm; 95% CI: 18.9-30.3) and HBR (15.2 lm; 95% CI: 9.8-20.5) was observed on days 10 and 3, respectively. CONCLUSIONS. The diameters of retinal blood vessels exhibited a dynamic response to hypoxia and bed rest, such that retinal vasodilation was smaller during combined bed rest and hypoxia than during hypoxic exposure