Roger Kölegård

Pressure-distension relationship in arteries and arterioles in response to 5 wk of horizontal bedrest

We hypothesized that exposure to prolonged recumbency (bedrest), and thus reductions of intravascular pressure gradients, increases pressure distension in arteries/arterioles in the legs. Ten subjects underwent 5 wk of horizontal bedrest. Pressure distension was investigated in arteries and arterioles before and after the bedrest, with the subject seated or supine in a hyperbaric chamber with either one arm or a lower leg protruding through a hole in the chamber door. Increased pressure in the vessels of the arm/leg was accomplished by increasing chamber pressure. Vessel diameter and flow were measured in the brachial and posterior tibial arteries using Doppler ultrasonography. Electrical tissue impedance was measured in the test limb. Bedrest increased (P < 0.01) pressure distension threefold in the tibial artery (from 8 +/- 7% to 24 +/- 11%) and by a third (P < 0.05) in the brachial artery (from 15 +/- 9% to 20 +/- 10%). The pressure-induced increase in tibial artery flow was more pronounced (P < 0.01) after (50 +/- 39 ml/min) than before (13 +/- 23 ml/min) bedrest, whereas the brachial artery flow response was unaffected by bedrest. The pressure-induced decrease in tissue impedance in the leg was more pronounced (P < 0.01) after (16 +/- 7%) than before (10 +/- 6%) bedrest, whereas bedrest did not affect the impedance response in the arm. Thus, withdrawal of the hydrostatic pressure gradients that act along the blood vessels in erect posture markedly increases pressure distension in dependent arteries and arterioles.

Motion sickness increases the risk of accidental hypothermia

Motion sickness (MS) has been found to increase body-core cooling during immersion in 28°C water, an effect ascribed to attenuation of the cold-induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619–623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15°C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (ΔTff), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, Pxa0<xa00.01). Also, the ΔTff response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (Pxa0<xa00.01 and Pxa0<xa00.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents.

Increased distensibility in dependent veins following prolonged bedrest

Displacement of blood to the lower portion of the body that follows a postural transition from recumbent to erect is augmented by a prolonged period of recumbency (bedrest). Information is scarce as to what extent this augmented blood-volume shift to dependent veins is attributable to increased distensibility of the veins. Accordingly, we studied the effect of 5xa0weeks of horizontal bedrest on the pressure–distension relationship in limb veins. Elevation of venous distending pressure was induced by exposure of the body except the tested limb to supra-atmospheric pressure with the subject seated in a pressure chamber with one arm, or supine with a lower leg, protruding through a hole in the chamber door. Diameter changes in response to an increase of intravenous pressure (distensibility) from 60 to about 140xa0mmHg were measured in the brachial and posterior tibial veins using ultrasonographic techniques. Prior to bedrest, the distensibility was substantially less in the tibial than in the brachial vein. Bedrest increased (Pxa0<xa00.01) pressure distension in the tibial vein by 86% from 7xa0±xa03% before to 13xa0±xa03% after bedrest. In the brachial vein, bedrest increased (Pxa0<xa00.05) pressure distension by 36% from 14xa0±xa05% before to 19xa0±xa05% after bedrest. Thus, removal of the gravity-dependent pressure components that act along the blood vessels in erect posture increases the distensibility of dependent veins.

The Effect of Normobaric Hypoxic Confinement on Metabolism, Gut Hormones, and Body Composition

To assess the effect of normobaric hypoxia on metabolism, gut hormones, and body composition, 11 normal weight, aerobically trained (O2peak: 60.6 ± 9.5 ml·kg−1·min−1) men (73.0 ± 7.7 kg; 23.7 ± 4.0 years, BMI 22.2 ± 2.4 kg·m−2) were confined to a normobaric (altitude ≃ 940 m) normoxic (NORMOXIA; PIO2 ≃ 133.2 mmHg) or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days) environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test (MTT), during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: −0.7 ± 0.2 kg; HYPOXIA: −0.9 ± 0.2 kg), but a significant increase in fat mass in NORMOXIA (0.23 ± 0.45 kg), but not in HYPOXIA (0.08 ± 0.08 kg). HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake.

Acute Effects of Normobaric Hypoxia on Hand-Temperature Responses During and After Local Cold Stress

The purpose was to investigate acute effects of normobaric hypoxia on hand-temperature responses during and after a cold-water hand immersion test. Fifteen males performed two right-hand immersion tests in 8°C water, during which they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI) and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were measured continuously with thermocouple probes; infrared thermography was also employed during the RW phase to map all segments of the hand. During the CWI phase, the average skin temperature (Tavg) of the fingers did not differ between the conditions (AIR: 10.2 ± 0.5°C, HYPO: 10.0 ± 0.5°C; p = 0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5 ± 3.4°C; HYPO: 22.0 ± 3.8°C; p = 0.002); a response that was alike in all regions of the immersed hand. Accordingly, present findings suggest that acute exposure to normobaric hypoxia does not aggravate the cold-induced drop in hand temperature of normothermic males. Still, hypoxia markedly impairs the rewarming responses of the hand.

PlanHab: hypoxia exaggerates the bed-rest-induced reduction in peak oxygen uptake during upright cycle ergometry.

The study examined the effects of hypoxia and horizontal bed rest, separately and in combination, on peak oxygen uptake (V̇o2 peak) during upright cycle ergometry. Ten male lowlanders underwent three 21-day confinement periods in a counterbalanced order: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PiO2 ) = 133.1 ± 0.3 mmHg]; 2) hypoxic bed rest (HBR; PiO2 = 90.0 ± 0.4 mmHg), and 3) hypoxic ambulation (HAMB; PiO2 = 90.0 ± 0.4 mmHg). Before and after each confinement, subjects performed two incremental-load trials to exhaustion, while inspiring either room air (AIR), or a hypoxic gas (HYPO; PiO2 = 90.0 ± 0.4 mmHg). Changes in regional oxygenation of the vastus lateralis muscle and the frontal cerebral cortex were monitored with near-infrared spectroscopy. Cardiac output (CO) was recorded using a bioimpedance method. The AIR V̇o2 peak was decreased by both HBR (∼13.5%; P ≤ 0.001) and NBR (∼8.6%; P ≤ 0.001), with greater drop after HBR (P = 0.01). The HYPO V̇o2 peak was also reduced by HBR (-9.7%; P ≤ 0.001) and NBR (-6.1%; P ≤ 0.001). Peak CO was lower after both bed-rest interventions, and especially after HBR (HBR: ∼13%, NBR: ∼7%; P ≤ 0.05). Exercise-induced alterations in muscle and cerebral oxygenation were blunted in a similar manner after both bed-rest confinements. No changes were observed in HAMB. Hence, the bed-rest-induced decrease in V̇o2 peak was exaggerated by hypoxia, most likely due to a reduction in convective O2 transport, as indicated by the lower peak values of CO.

Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise

The study examined the effects of a 10‐day normobaric hypoxic confinement (FiO2: 0.14), with [hypoxic exercise training (HT); nu2009=u20098)] or without [hypoxic ambulatory (HA; nu2009=u20096)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30u2009min in 8u2009°C water [cold water immersion (CWI)], followed by a 15‐min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (−1.3u2009°C; Pu2009=u20090.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5u2009°C; Pu2009≤u20090.05) and RW (+2.4u2009°C; Pu2009≤u20090.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold‐induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.

Repeated exposures to moderately increased intravascular pressure increases stiffness in human arteries and arterioles.

Objective The aim was to investigate whether repeated exposures to moderate pressure elevations in the blood vessels of the arms (pressure training) affect pressure distension in arteries/arterioles of healthy individuals. Methods Pressure training and vascular pressure–distension determinations were conducted with the participant (nu200a=u200a11) seated in a pressure chamber with one arm slipped through a hole in the chamber door. Intravascular pressure was increased by elevating chamber pressure. Before pressure training, one arm was investigated (control arm) during stepwise increases in chamber pressure to 180u200ammHg. Diameter and flow were measured in the brachial artery using ultrasonography/Doppler techniques. Thereafter, the contralateral arm underwent pressure training consisting of fifteen 40-min sessions during 5 weeks; local intravascular pressures were elevated by 65–105u200ammHg during the sessions. After pressure training, pressure–distension relationships were examined in both the trained arm and the control arm. Results Pressure training reduced (Pu200a<u200a0.01) arterial pressure distension by 46u200a±u200a18%. Likewise, the pressure-induced increase in arterial flow was less after (350u200a±u200a249%) than before (685u200a±u200a216%) pressure training. The pressure training-induced reductions in arterial/arteriolar pressure distension were reversed 5 weeks after pressure training. Conclusion Thus, the in-vivo wall stiffness in arteries and arterioles increases markedly in response to intermittent, moderate increments of transmural pressure during 5 weeks. The findings are compatible with the notion that local load serves as ‘a prime mover’ in the development of vascular changes in hypertension.

PlanHab: Hypoxia counteracts the erythropoietin suppression, but seems to exaggerate the plasma volume reduction induced by 3 weeks of bed rest

The study examined the distinct and synergistic effects of hypoxia and bed rest on the erythropoietin (EPO) concentration and relative changes in plasma volume (PV). Eleven healthy male lowlanders underwent three 21‐day confinement periods, in a counterbalanced order: (1) normoxic bed rest (NBR; PIO2: 133.1 ± 0.3 mmHg); (2) hypoxic bed rest (HBR; PIO2: 90.0 ± 0.4 mmHg, ambient simulated altitude of ~4000 m); and (3) hypoxic ambulation (HAMB; PIO2: 90.0 ± 0.4 mmHg). Blood samples were collected before, during (days 2, 5, 14, and 21) and 2 days after each confinement to determine EPO concentration. Qualitative differences in PV changes were also estimated by changes in hematocrit and hemoglobin concentration along with concomitant changes in plasma renin concentration. NBR caused an initial reduction in EPO by ~39% (P = 0.04). By contrast, HBR enhanced EPO (P = 0.001), but the increase was less than that induced by HAMB (P < 0.01). All three confinements caused a significant reduction in PV (P < 0.05), with a substantially greater drop in HBR than in the other conditions (P < 0.001). Thus, present results suggest that hypoxia prevents the EPO suppression, whereas it seems to exaggerate the PV reduction induced by bed rest.

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 50xa0%. Conversely, prolonged reduction of arterial/arteriolar pressure in the lower body by 5xa0weeks 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.