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  • 1. Debevec, Tadej
    et al.
    Pialoux, Vincent
    Ehrström, Sabine
    Ribon, Alexandra
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, Igor B.
    Millet, Gregoire P.
    FemHab: The effects of bed rest and hypoxia on oxidative stress in healthy women2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 8, p. 930-938Article in journal (Refereed)
    Abstract [en]

    Independently, both inactivity and hypoxia augment oxidative stress. This study, part of the FemHab project, investigated the combined effects of bed rest-induced unloading and hypoxic exposure on oxidative stress and antioxidant status. Healthy, eumenorrheic women were randomly assigned to the following three 10-day experimental interventions: normoxic bed rest (NBR; n = 11; PIO2 = 133 mmHg), normobaric hypoxic bed rest (HBR; n = 12; PIO2 = 90 mmHg), and ambulatory hypoxic confinement (HAMB; n = 8: PIO2 = 90 mmHg). Plasma samples, obtained before (Pre), during (D2, D6), immediately after (Post) and 24 h after (Post + 1) each intervention, were analyzed for oxidative stress markers [advanced oxidation protein products (AOPP), malondialdehyde (MDA), and nitrotyrosine], antioxidant status [ superoxide dismutase (SOD), catalase, ferric-reducing antioxidant power (FRAP), glutathione peroxidase (GPX), and uric acid (UA)], NO metabolism end-products (NOx), and nitrites. Compared with baseline, AOPP increased in NBR and HBR on D2 (+ 14%; + 12%; P < 0.05), D6 (+ 19%; + 15%; P < 0.05), and Post (+ 22%; + 21%; P < 0.05), respectively. MDA increased at Post + 1 in NBR (+ 116%; P < 0.01) and D2 in HBR (+114%; P < 0.01) and HAMB (+ 95%; P < 0.05). Nitrotyrosine decreased (-45%; P < 0.05) and nitrites increased (+46%; P < 0.05) at Post + 1 in HAMB only. Whereas SOD was higher at D6 (+ 82%) and Post + 1 (+ 67%) in HAMB only, the catalase activity increased on D6 (128%) and Post (146%) in HBR and HAMB, respectively (P < 0.05). GPX was only reduced on D6 (- 20%; P < 0.01) and Post (- 18%; P < 0.05) in HBR. No differences were observed in FRAP and NOx. UA was higher at Post in HBR compared with HAMB (P < 0.05). These data indicate that exposure to combined inactivity and hypoxia impairs prooxidant/antioxidant balance in healthy women. Moreover, habitual activity levels, as opposed to inactivity, seem to blunt hypoxia-related oxidative stress via antioxidant system upregulation.

  • 2.
    Eiken, Ola
    et al.
    Karolinska Institutet.
    Hesser, C.M.
    Lind, F.
    Thorsson, A.
    Tesch, P.A.
    Human skeletal muscle function and metabolism during intense exercise at high O2 and N2 pressures1987In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 63, no 2, p. 571-575Article in journal (Refereed)
    Abstract [en]

    The maximal contractile force (peak torque) of the quadriceps femoris was studied during 60 repeated unilateral dynamic knee extensions in nine subjects under three different conditions, viz., during air breathing at normal (1 ATA) and raised (6 ATA) ambient pressures and during O2 breathing at 1.3 ATA. In six subjects the electromyographic (EMG) activity of the working muscle was recorded. Muscle biopsies were obtained from the vastus lateralis before, immediately after, and 1 min after exercise. Tissue specimens were subsequently assayed for various muscle metabolites. Peak torque, as an average of the 60 knee extensions, was higher (P less than 0.05) at 1.3 ATA than at 6 or 1 ATA. Peak torque of the exercising muscle declined more rapidly at 1 ATA than at 1.3 ATA, differing in the final 24 contractions by 14%. At 6 ATA peak torque of the initial 12 contractions was 6% lower (P less than 0.05) than at 1 ATA but equaled 1-ATA values in the latter third of the exercise bout. Although the EMG activity at 1 ATA increased relative to that at 6 ATA as exercise proceeded, the rate of force decline was greater at 1 ATA. Despite greater total work produced at 1.3 ATA than at 1 ATA, the metabolic response to exercise was not substantially altered at increased O2 pressure. However, the restitution rate of energy-rich phosphagens and the elimination of lactate during recovery were greater (P less than 0.05) at 1.3 ATA. These results suggest that hyperoxia may enhance the rate of energy release, whereas high N2 pressure and/or high hydrostatic pressure seem to interfere with neuromuscular activity.

  • 3.
    Eiken, Ola
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, IB
    Kounalakis, SN
    Kölegård, Roger
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Pressure distension in leg vessels as influenced by prolonged bed rest and a pressure habituation regimen2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 12, p. 1458-1465Article in journal (Refereed)
    Abstract [en]

    Bed rest increases pressure distension in arteries, arterioles, and veins of the leg. We hypothesized that bed-rest-induced deconditioning of leg vessels is governed by the removal of the local increments in transmural pressure induced by assuming erect posture and, therefore, can be counteracted by intermittently increasing local transmural pressure during the bed rest. Ten men underwent 5 wk of horizontal bed rest. A subatmospheric pressure (-90 mmHg) was intermittently applied to one lower leg [pressure habituation (PH) leg]. Vascular pressure distension was investigated before and after the bed rest, both in the PH and control (CN) leg by increasing local distending pressure, stepwise up to +200 mmHg. Vessel diameter and blood flow were measured in the posterior tibial artery and vessel diameter in the posterior tibial vein. In the CN leg, bed rest led to 5-fold and 2.7-fold increments (P < 0.01) in tibial artery pressure-distension and flow responses, respectively, and to a 2-fold increase in tibial vein pressure distension. In the PH leg, arterial pressure-distension and flow responses were unaffected by bed rest, whereas bed rest led to a 1.5-fold increase in venous pressure distension. It thus appears that bed-rest-induced deconditioning of leg arteries, arterioles, and veins is caused by removal of gravity-dependent local pressure loads and may be abolished or alleviated by a local pressure-habituation regimen.

  • 4.
    Gennser, Mikael
    et al.
    Swedish Defence Research Agency.
    Blogg, S.L.
    Oxygen or carbogen breathing before simulated submarine escape2008In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 104, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Raised internal pressure in a distressed submarine increases the risk of bubble formation and decompression illness after submarine escape. The hypothesis that short periods of oxygen breathing before submarine escape would reduce decompression stress was tested, using Doppler-detectable venous gas emboli as a measure. Twelve goats breathed oxygen for 15 min at 0.1 MPa before exposure to a simulated submarine escape profile to and from 2.5 MPa (240 m/seawater), whereas 28 control animals underwent the same dive without oxygen prebreathe. No decompression sickness (DCS) occurred in either of these two groups. Time with high bubble scores (Kisman-Masurel >or=3) was significantly (P < 0.001) shorter in the prebreathe group. In a second series, 30 goats breathed air at 0.2 MPa for 6 h. Fifteen minutes before escape from 2.5 MPa, animals were provided with either air (n = 10), oxygen (n = 12), or carbogen (97.5% O(2) and 2.5% CO(2)) gas (n = 8) as breathing gas. Animals breathed a hyperoxic gas (60% O(2)-40% N(2)) during the escape. Two animals (carbogen group) suffered oxygen convulsions during the escape but recovered on surfacing. Only one case of DCS occurred (carbogen group). The initial bubble score was reduced in the oxygen group (P < 0.001). The period with bubble score of Kisman-Masurel >or=3 was also significantly reduced in the oxygen group (P < 0.001). Oxygen breathing before submarine escape reduces initial bubble scores, although its significance in reducing central nervous system DCS needs to be investigated further.

  • 5.
    Grönkvist, Mikael
    et al.
    Swedish Defence Research Agency.
    Bergsten, Eddie
    Swedish Defence Research Agency.
    Eiken, Ola
    Swedish Defence Research Agency.
    Gustafsson, Per M
    Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit2003In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 94, no 4, p. 1353-1364Article in journal (Refereed)
    Abstract [en]

    This study assessed the effects of increased gravity in the head-to-foot direction (+G(z)) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (V(TG)), and ventilation distribution by using inert- gas washout. Normalized phase III slope (Sn(III)) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF(6) and He in a human centrifuge at +1 to +3 G(z) wearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, V(TG), and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased V(TG), overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 G(z) reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +G(z) impairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.

  • 6.
    Grönkvist, Mikael
    et al.
    Swedish Defence Research Agency.
    Bergsten, Eddie
    Swedish Defence Research Agency.
    Gustafsson, Per M.
    Effects of body posture and tidal volume on inter- and intraregional ventilation distribution in healthy men2002In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 92, no 2, p. 634-642Article in journal (Refereed)
    Abstract [en]

    The influences of body posture and tidal volume (VT) on inter- and intraregional ventilation inhomogeneity were assessed by normalized phase III slope (Sn(III)) analysis of multiple-breath washout recordings of SF(6) and He in 11 healthy men. Washouts with target VT of 750, 1,000, and 1,250 ml were performed standing and supine. A linear-fit method was used to establish the contributions of convection-dependent (interregional) (cdi) and diffusion-convection interaction-dependent (intraregional) inhomogeneity (dcdi). Overall inhomogeneity was defined as the sum of cdi and dcdi. The difference in first-breath Sn(III) for SF(6) vs. He, the (SF(6) - He)Sn(III), served as an index of intra-acinar inhomogeneity. Multiple-regression analysis revealed greater cdi supine vs. standing (P < 0.001) but no significant effects of posture on dcdi or overall inhomogeneity. Larger VT were associated with greater cdi (P < 0.001), particularly when supine, but reduced dcdi (P < 0.001), overall inhomogeneity (P < 0.001), and (SF(6) - He)Sn(III) (P = 0.031). In conclusion, during resting breathing overall and intraregional ventilation inhomogeneities remain unchanged when the supine posture is assumed and improve with larger VT, but supine posture and larger breaths result in greater interregional inhomogeneities.

  • 7. Gustafsson, P M
    et al.
    Eiken, Ola
    Swedish Defence Research Agency.
    Grönkvist, Mikael
    Swedish Defence Research Agency.
    Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths2001In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 91, no 2, p. 637-644Article in journal (Refereed)
    Abstract [en]

    The effects of increased gravity in the head-to-foot direction (+G(z)) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He phase III slopes increased proportionally with increasing gravity, but the (SF(6) -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He slopes significantly but resulted in increased (SF(6) -- He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.

  • 8. Jaki Mekjavic, P
    et al.
    Lenassi, E
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, IB
    Effect of acute hypercapnia during 10-day hypoxic bed rest on posterior eye structures.2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 10, p. 1241-1248Article in journal (Refereed)
  • 9. Kaijser, L.
    et al.
    Sundberg, C. J.
    Eiken, Ola
    Karolinska Institutet.
    Nygren, A.
    Esbjörnsson, M.
    Sylvén, C.
    Jansson, E.
    Muscle oxidative capacity and work performance after training under local leg ischemia1990In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 69, no 2, p. 785-787Article in journal (Refereed)
    Abstract [en]

    Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg.

  • 10. Lindholm, P
    et al.
    Sundblad, Patrik
    KTH, School of Technology and Health (STH), Environmental Physiology (Closed 20130701).
    Linnarsson, D
    Oxygen-conserving effects of apnea in exercising men.1999In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 87, no 6, p. 2122-2127Article in journal (Refereed)
    Abstract [en]

    We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O(2) conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O(2) saturation (Sa(O(2)); pulse oximetry) were recorded continuously. Responses (DeltaHR, DeltaMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O(2) desaturation (DeltaSa(O(2))/Deltat) was determined during the same time interval. During apnea, DeltaSaO(2)/Deltat had a significant negative correlation to the amplitudes of DeltaHR and DeltaMAP (r(2) = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest DeltaSa(O(2))/Deltat. DeltaHR and DeltaMAP were much larger during A (-44 +/- 8 beats/min, +49 +/- 4 mmHg, respectively) than during R maneuver (+3 +/- 3 beats/min, +30 +/- 5 mmHg, respectively). DeltaSa(O(2))/Deltat during A and R maneuvers was -1.1 +/- 0.1 and -2.2 +/- 0.2% units/s, respectively, and nadir Sa(O(2)) values were 58 +/- 4 and 42 +/- 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O(2) conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.

  • 11. Lindholm, Peter
    et al.
    Ekborn, Andreas
    Öberg, Daniel
    Gennser, Mikael
    Swedish Defence Research Agency.
    Pulmonary edema and hemoptysis after breath-hold diving at residual volume2008In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 104, no 4, p. 912-917Article in journal (Refereed)
    Abstract [en]

    To simulate pressure effects and experience thoracic compression while breath-hold diving in a relatively safe environment, competitive breath-hold divers exhale to residual volume before diving in a swimming pool, thus compressing the chest even at depth of only 3-6 m. The study was undertaken to investigate whether such diving could cause pulmonary edema and hemoptysis. Eleven volunteer breath-hold divers who regularly dive on full exhalation performed repeated dives to 6 m during a 20-min period. The subjects were studied with dynamic spirometry, video-fibernasolaryngoscopy, and single-breath diffusion capacity of carbon monoxide (Dl(CO)). The duration of dives with empty lungs ranged from 30 to 120 s. Postdiving forced vital capacity (FVC) was reduced from mean (SD) 6.57 +/- 0.88 to 6.23 +/- 1.02 liters (P < 0.05), and forced expiratory volume during the first second (FEV(1.0)) was reduced from 5.09 +/- 0.64 to 4.59 +/- 0.72 liters (P < 0.001) (n = 11). FEV(1.0)/FVC was 0.78 +/- 0.05 prediving and 0.74 +/- 0.05 postdiving (P < 0.001) (n = 11). All subjects reported a (reversible) change in their voice after diving, irritation, and slight congestion in the larynx. Fresh blood that originated from somewhere below the vocal cords was found by laryngoscopy in two subjects. Dl(CO)/alveolar ventilation (Va) was 1.56 +/- 0.17 mmol.kPa(-1).min(-1).l(-1) before diving. After diving, the Dl(CO)/Va increased to 1.72 +/- 0.24 (P = 0.001), but 20 min later it was indistinguishable from the predive value: 1.57 +/- 0.20 (n = 11). Breath-hold diving with empty lungs to shallow depths can induce hemoptysis in healthy subjects. Edema was possibly present in the lower airways, as suggested by reduced dynamic spirometry.

  • 12. Linnarsson, D.
    et al.
    Ornhagen, H.
    Gennser, Mikael
    Berg, H.
    Breathing volumes and gas exchange during simulated rapid free ascent from 100 msw1993In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 74, no 3, p. 1293-1298Article in journal (Refereed)
    Abstract [en]

    The crew of a disabled submarine can be rescued by means of free ascent through the water to the surface. Pulmonary gas exchange was studied during simulated rapid free ascent in subjects standing immersed to the neck in a pressure chamber. The pressure was rapidly increased to 1.1 MPa [100 meters seawater (msw)] followed by decompression at 0.03 MPa/s (3 msw/s). Effective inspired tidal volume, as estimated by an Ar dilution method, fell gradually to zero during decompression from 20 to 0 msw. Directly determined expired tidal volumes were increased up to two to three times at the time of return to surface pressure compared with pre- and postdecompression volumes. End-tidal PCO2 was increased on compression and fell to a nadir of 3.4 kPa (25 Torr) at the time of return to surface pressure. Thus, intrapulmonary gas expansion caused simultaneous inspiratory hypoventilation and expiratory hyperventilation. If O2-enriched gas is to be used to reduce the risk of decompression sickness, it should be administered early during decompression to alter the intrapulmonary gas composition. The time course of arterial PCO2 changes as reflected by end-tidal values during short-lasting compression/decompression would act to promote inert gas supersaturation in the brain.

  • 13. Linnarsson, D
    et al.
    Zou, L
    Chuang, C.C.
    Li, G
    Gao, F
    Mekjavic, P.J.
    Dua, H
    Amoaku, W
    Macdonald, I.A.
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, I.B.
    Commentaries on Viewpoint: Standardization of bed rest studies in the spaceflight context.2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 121, no 1, p. 350-351Article in journal (Refereed)
  • 14. Mekjavic, Igor B.
    et al.
    Eiken, Ola
    Swedish Defence Research Agency.
    Contribution of thermal and nonthermal factors to the regulation of body temperature in humans2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 100, no 6, p. 2065-2072Article in journal (Refereed)
    Abstract [en]

    The set point has been used to define the regulated level of body temperature, suggesting that displacements of core temperature from the set point initiate heat production (HP) and heat loss (HL) responses. Human and animal experiments have demonstrated that the responses of sweating and shivering do not coincide at a set point but rather establish a thermoeffector threshold zone. Neurophysiological studies have demonstrated that the sensor-to-effector pathways for HP and HL overlap and, in fact, mutually inhibit each other. This reciprocal inhibition theory, presumably reflecting the manner in which thermal factors contribute to homeothermy in humans, does not incorporate the effect of nonthermal factors on temperature regulation. The present review examines the actions of these nonthermal factors within the context of neuronal models of temperature regulation, suggesting that examination of these factors may provide further insights into the nature of temperature regulation. It is concluded that, although there is no evidence to doubt the existence of the HP and HL pathways reciprocally inhibiting one another, it appears that such a mechanism is of little consequence when comparing the effects of nonthermal factors on the thermoregulatory system, since most of these factors seem to exert their influence in the region after the reciprocal cross-inhibition. At any given moment, both thermal and several nonthermal factors will be acting on the thermoregulatory system. It may, therefore, not be appropriate to dismiss the contribution of either when discussing the regulation of body temperature in humans.

  • 15. Mekjavic, Igor B.
    et al.
    Rogelj, Klemen
    Radobuljac, Maja
    Eiken, Ola
    Swedish Defence Research Agency.
    Inhalation of warm and cold air does not influence brain stem or core temperature in normothermic humans2002In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 93, no 1, p. 65-69Article in journal (Refereed)
    Abstract [en]

    The present study tested the hypothesis that inhalation rewarming provides a thermal increment to central neural structures adjacent to the nasopharyngeal region. Auditory-evoked brain stem responses of 14 subjects (7 men and 7 women) were monitored for 25 min while they inspired room air (24 degrees C) followed by hot air (41 degrees C) saturated with water vapor and cold dry air (-1 degrees C). The latencies of peaks I, III, and V and the interpeak latencies (IPLs) I-III, III-V, and I-V were compared among the three conditions with a repeated-measures ANOVA. Changes in IPLs are sensitive markers of changes in brain stem temperature. Tympanic temperature (T(ty)) was measured with an infrared tympanic thermometer. There were no significant differences in T(ty), peak latencies I, III, and V, and IPLs I-III, III-V, and I-V. The results indicate that inhalation of hot and cold air does not influence T(ty), nor does it influence the temperature of the brain stem. We conclude that inhalation rewarming is not capable of warming the vital central neural structures adjacent to the naropharynx.

  • 16. Mekjavić, I. B.
    et al.
    Savić, S. A.
    Eiken, Ola
    Karolinska Institutet.
    Nitrogen narcosis attenuates shivering thermogenesis1995In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 78, no 6, p. 2241-2244Article in journal (Refereed)
    Abstract [en]

    Thermoregulatory responses of eight healthy subjects (six men and two women) were compared when they were head-out immersed in 15 degrees C water at both 1 and 6 ATA. Both trials were conducted in a hyperbaric chamber. During the immersions, esophageal temperature (T(es)) and skin temperature at two sites (chest and calf) were recorded at minute intervals. Oxygen uptake was determined at 5-min intervals with the Douglas bag method. The order of the two trials was alternated. The rate of T(es) cooling was greater during the 6-ATA trial [2.1 +/- 0.5 degrees C/h (SE)] than during the 1-ATA trial (1.3 +/- 0.5 degrees C/h; P < 0.01). Despite the greater rate of core cooling, and presumably a greater thermal drive for shivering, the oxygen uptake response for a similar decrement in T(es) was lower during exposure to 6 than to 1 ATA (P < 0.05). Also, for similar displacement in T(es), the subjects perceived the immersions at 6 ATA to be less cold than those at 1 ATA (P < 0.05). It is concluded that the development of hypothermia in compressed-air divers may be due, in large part, to the attenuation of heat production and cold perception. Most likely, the observed effects on the autonomic responses and thermal perception are due to an inhibitory action of hyperbaric nitrogen on central neural structures involved in temperature regulation.

  • 17.
    Montmerle, S.
    et al.
    Karolinska Institutet.
    Sundblad, Patrik
    Karolinska Institutet, Sweden.
    Linnarsson, D.
    Karolinska Institutet.
    Residual heterogeneity of intra- and interregional pulmonary perfusion in short-term microgravity2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 98, no 6, p. 2268-2277Article in journal (Refereed)
    Abstract [en]

    We hypothesized that the perfusion heterogeneity in the human, upright lung is determined by nongravitational more than gravitational factors. Twelve and six subjects were studied during two series of parabolic flights. We used cardiogenic oscillations of O(2)/SF(6) as an indirect estimate of intraregional perfusion heterogeneity (series 1) and phase IV amplitude (P(4)) as a indirect estimate of interregional perfusion heterogeneity (series 2). A rebreathing-breath holding-expiration maneuver was performed. In flight, breath holding and expiration were performed either in microgravity (0 G) or in hypergravity. Controls were performed at normal gravity (1 G). In series 1, expiration was performed at 0 G. Cardiogenic oscillations of O(2)/SF(6) were 19% lower when breath holding was performed at 0 G than when breath holding was performed at 1 G [means (SD): 1.7 (0.3) and 2.3 (0.6)% units] (P = 0.044). When breath holding was performed at 1.8 G, values did not differ from 1-G control [2.6 (0.8)% units, P = 0.15], but they were 17% larger at 1.8 G than at 1 G. In series 2, expiration was performed at 1.7 G. P(4) changed with gravity (P < 0.001). When breath holding was performed at 0 G, P(4) values were 45 (46)% of control. When breath holding was performed at 1.7 G, P(4) values were 183 (101)% of control. We conclude that more than one-half of indexes of perfusion heterogeneity at 1 G are caused by nongravitational mechanisms.

  • 18. Oldmixon, E. H.
    et al.
    Carlsson, Kjell
    KTH, Superseded Departments, Physics.
    Kuhn, C.
    Butler, J. P.
    Hoppin, F. G.
    alpha-Actin: disposition, quantities, and estimated effects on lung recoil and compliance2001In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 91, no 1, p. 459-473Article in journal (Refereed)
    Abstract [en]

    We have investigated the basis and implications of pneumoconstriction by measuring disposition and quantities of alpha -smooth muscle actin in rat and guinea pig lungs and modeling its effects on lung recoil and compliance. A robust marker of contractility, alpha -smooth muscle actin appears in smooth muscle or myofibroblast-like cells in pleura, airways, blood vessels, and alveolar ductal tissues. In each site, we measured its transected area by immunofluorescent staining and frequency-modulated scanning confocal microscopy. We incorporated these data in a model of the parenchyma consisting of an extensive elastic network with embedded contractile structures. We conclude that contraction at any one of these sites alone can decrease parenchymal compliance by 20-30% during tidal breathing. This is due mostly to the stiffness of activated contractile elements undergoing passive cycling; constant muscle tension would have little effect. The magnitude of the effect corresponds with known responses of the lung to hypocapnia, consistent with a homeostatic function in which gas exchange is defended by redistributing ventilation away from overventilated units.

  • 19. Rohdin, M
    et al.
    Petersson, J
    Sundblad, Patrik
    KTH, School of Technology and Health (STH), Environmental Physiology (Closed 20130701).
    Mure, M
    Glenny, RW
    Lindahl, SG
    Linnarsson, D
    Effects of gravity on lung diffusing capacity and cardiac output in prone and supine humans.2003In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 95, no 1, p. 3-10Article in journal (Refereed)
    Abstract [en]

    Both in normal subjects exposed to hypergravity and in patients with acute respiratory distress syndrome, there are increased hydrostatic pressure gradients down the lung. Also, both conditions show an impaired arterial oxygenation, which is less severe in the prone than in the supine posture. The aim of this study was to use hypergravity to further investigate the mechanisms behind the differences in arterial oxygenation between the prone and the supine posture. Ten healthy subjects were studied in a human centrifuge while exposed to 1 and 5 times normal gravity (1 G, 5 G) in the anterioposterior (supine) and posterioanterior (prone) direction. They performed one rebreathing maneuver after approximately 5 min at each G level and posture. Lung diffusing capacity decreased in hypergravity compared with 1 G (ANOVA, P = 0.002); it decreased by 46% in the supine posture compared with 25% in the prone (P = 0.01 for supine vs. prone). At the same time, functional residual capacity decreased by 33 and 23%, respectively (P < 0.001 for supine vs. prone), and cardiac output by 40 and 31% (P = 0.007 for supine vs. prone), despite an increase in heart rate of 16 and 28% (P < 0.001 for supine vs. prone), respectively. The finding of a more impaired diffusing capacity in the supine posture compared with the prone at 5 G supports our previous observations of more severe arterial hypoxemia in the supine posture during hypergravity. A reduced pulmonary-capillary blood flow and a reduced estimated alveolar volume can explain most of the reduction in diffusing capacity when supine.

  • 20.
    Rohdin, M.
    et al.
    Karolinska Institutet.
    Sundblad, Patrik
    Karolinska Institutet, Sweden.
    Linnarsson, D.
    Karolinska Institutet.
    Effects of hypergravity on the distributions of lung ventilation and perfusion in sitting humans assessed with a simple two-step maneuver2004In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 96, no 4, p. 1470-1477Article in journal (Refereed)
    Abstract [en]

    Increased gravity impairs pulmonary distributions of ventilation and perfusion. We sought to develop a method for rapid, simultaneous, and noninvasive assessments of ventilation and perfusion distributions during a short-duration hypergravity exposure. Nine sitting subjects were exposed to one, two, and three times normal gravity (1, 2, and 3 G) in the head-to-feet direction and performed a rebreathing and a single-breath washout maneuver with a gas mixture containing C(2)H(2), O(2), and Ar. Expirograms were analyzed for cardiogenic oscillations (COS) and for phase IV amplitude to analyze inhomogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. COS were normalized for changes in stroke volume. COS for Ar increased from 1-G control to 128 +/- 6% (mean +/- SE) at 2 G (P = 0.02 for 1 vs. 2 G) and 165 +/- 13% at 3 G (P = 0.002 for 2 vs. 3 G). Corresponding values for CO(2)/Ar were 135 +/- 12% (P = 0.04) and 146 +/- 13%. Phase IV amplitude for Ar increased to 193 +/- 39% (P = 0.008) at 2 G and 229 +/- 51% at 3 G compared with 1 G. Corresponding values for CO(2)/Ar were 188 +/- 29% (P = 0.02) and 219 +/- 18%. We conclude that not only large-scale ventilation and perfusion inhomogeneities, as reflected by phase IV amplitude, but also smaller-scale inhomogeneities, as reflected by the ratio of COS to stroke volume, increase with hypergravity. Except for small-scale ventilation distribution, most of the impairments observed at 3 G had been attained at 2 G. For some of the parameters and gravity levels, previous comparable data support the present simplified method.

  • 21. Salvadego, Desy
    et al.
    Keramidas, Michail E.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Brocca, Lorenza
    Domenis, Rossana
    Mavelli, Irene
    Rittweger, Jörn
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, Igor B.
    Grassi, Bruno
    LunHab: Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans.2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 121, no 1Article in journal (Refereed)
    Abstract [en]

    An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age, 24.1 +/- 1.7 yr mean +/- SD) before (CTRL) and after a 10-day horizontal bed rest carried out in normoxia (N-BR) or hypoxia (H-BR, FIO2 = 0.147). H-BR was designed to simulate planetary habitats. Pulmonary O-2 uptake ((V) over dotO(2)) and vastus lateralis fractional O-2 extraction (changes in deoxygenated hemoglobin + myoglobin concentration, Delta[deoxy(Hb + Mb)] evaluated using near-infrared spectroscopy) were evaluated in normoxia and during an incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE (V) over dotO(2peak) and Delta[deoxy(Hb + Mb)] peak were lower (P < 0.05) after both N-BR and H-BR than during CTRL; during KE the variables were lower after N-BR but not after H-BR. During CE the overshoot of Delta[deoxy(Hb + Mb)] during constant work rate exercise was greater in N-BR and H-BR than CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by either intervention. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O-2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O-2 supply and utilization and peripheral O-2 diffusion. Superposition of hypoxia on bed rest did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by bed rest. The effects of longer exposures will have to be determined.

  • 22.
    Siebenmann, C
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology. University of Zürich, Switzerland.
    Cathomen, A
    Hug, M
    Keiser, S
    Lundby, AK
    Hilty, MP
    Goetze, JP
    Rasmussen, P
    Lundby, C
    Hemoglobin mass and intravascular volume kinetics during and after exposure to 3,454 m altitude.2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 10Article in journal (Refereed)
    Abstract [en]

    High altitude (HA) exposure facilitates a rapid contraction of plasma volume (PV) and a slower occurring expansion of hemoglobin mass (Hbmass). The kinetics of the Hbmass expansion has never been examined by multiple repeated measurements and this was our primary study aim. The second aim was to investigate the mechanisms mediating the PV contraction. Nine healthy, normally-trained sea-level (SL) residents (8 males, 1 female) sojourned for 28 days at 3,454 m. Hbmass was measured and PV estimated by carbon monoxide re-breathing at SL, on every fourth day at HA, and one and two weeks upon return to SL. Four weeks at HA increased Hbmass by 5.26 % (range 2.5 - 11.1 %; p<0.001). The individual Hbmass increases commenced with up to 12 days delay and reached a maximal rate of 4.04 ± 1.02 g.d-1 after 14.9 ± 5.2 days. The probability for Hbmass to plateau increased steeply after 20-24 days. Upon return to SL Hbmass decayed by -2.46 ± 2.3 g.d-1, reaching values similar to baseline after two weeks. PV, aldosterone concentration and renin activity were reduced at HA (p<0.001) while the total circulating protein mass remained unaffected. In summary the Hbmass response to HA exposure followed a sigmoidal pattern with a delayed onset and a plateau after ~3 weeks. The decay rate of Hbmass upon descent to SL did not indicate major changes in the rate of erythrolysis. Moreover, our data supports that PV contraction at HA is regulated by the renin-angiotensin-aldosterone axis and not by changes in oncotic pressure.

  • 23. Simpson, Elizabeth J.
    et al.
    Debevec, Tadej
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, Igor
    Macdonald, Ian A.
    PlanHab: the combined and separate effects of 16 days of bed rest and normobaric hypoxic confinement on circulating lipids and indices of insulin sensitivity in healthy men2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 8, p. 947-955Article in journal (Refereed)
    Abstract [en]

    PlanHab is a planetary habitat simulation study. The atmosphere within future space habitats is anticipated to have reduced PO2, but information is scarce as to how physiological systems may respond to combined exposure to moderate hypoxia and reduced gravity. This study investigated, using a randomized-crossover design, how insulin sensitivity, glucose tolerance, and circulating lipids were affected by 16 days of horizontal bed rest in normobaric normoxia [NBR: FIO2 = 0.209; PIO2 = 133.1 (0.3) mmHg], horizontal bed rest in normobaric hypoxia [HBR: FIO2 = 0.141 (0.004); PIO2 = 90.0 (0.4) mmHg], and confinement in normobaric hypoxia combined with daily moderate intensity exercise (HAMB). A mixed-meal tolerance test, with arterialized-venous blood sampling, was performed in 11 healthy, nonobese men (25-45 yr) before (V1) and on the morning of day 17 of each intervention (V2). Postprandial glucose and c-peptide response were increased at V2 of both bed rest interventions (P < 0.05 in each case), with c-peptide: insulin ratio higher at V2 in HAMB and HBR, both in the fed and fasted state (P < 0.005 in each case). Fasting total cholesterol was reduced at V2 in HAMB [-0.47 (0.36) mmol/l; P < 0.005] and HBR [-0.55 (0.41) mmol/l; P < 0.005]. Fasting HDL was lower at V2 in all interventions, with the reduction observed in HBR [-0.30 (0.21) mmol/l] greater than that measured in HAMB [-0.13 (0.14) mmol/l; P < 0.005] and NBR [-0.17 (0.15) mmol/l; P < 0.05]. Hypoxia did not alter the adverse effects of bed rest on insulin sensitivity and glucose tolerance but appeared to increase insulin clearance. The negative effect of bed rest on HDL was compounded in hypoxia, which may have implications for long-term health of those living in future space habitats.

  • 24. Sotiridis, Alexandros
    et al.
    Debevec, Tadej
    McDonnell, Adam C.
    Ciuha, Ursa
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Mekjavic, Igor B
    Exercise cardiorespiratory and thermoregulatory responses in normoxic, hypoxic and hot environment following 10-day continuous hypoxic exposure.2018In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601Article in journal (Refereed)
    Abstract [en]

    We examined the effects of acclimatization to normobaric hypoxia on aerobic performance and exercise thermoregulatory responses under normoxic, hypoxic and hot conditions. Twelve males performed tests of maximal oxygen uptake (V̇O2max) in normoxic (NOR), hypoxic (13.5% FiO2; HYP) and hot (35℃, 50% RH; HE) conditions in a randomized manner before and after a 10-day continuous normobaric hypoxic exposure (FiO2 = 13.65(0.35)%, PiO2 = 87(3) mmHg). The acclimatization protocol included daily exercise (60min @ 50% hypoxia-specific peak power output, Wpeak). All maximal tests were preceded by a steady-state exercise (30 min at 40% Wpeak) to assess the sweating response. Hematological data were assessed from venous blood samples obtained before and after acclimatization. V̇O2max increased by 10.7% (P = 0.002) and 7.9% (P = 0.03) from pre- to post-acclimatization in NOR and HE, respectively, whereas no differences were found in HYP (pre: 39.9(3.8) vs post: 39.4(5.1) mL.kg-1.min-1, P = 1.0). However, the increase in V̇O2max did not translate into increased Wpeak in either NOR or HE. Maximal heart rate and ventilation remained unchanged following acclimatization. Νo differences were noted in the sweating gain and thresholds independent of the acclimatization or environmental conditions. Hypoxic acclimatization markedly increased hemoglobin (P &lt; 0.001), hematocrit (P &lt; 0.001) and extracellular HSP72 (P = 0.01). These data suggest that 10 days of normobaric hypoxic acclimatization combined with moderate-intensity exercise training improves V̇O2max in NOR and HE, but does not seem to affect exercise performance or thermoregulatory responses in any of the tested environmental conditions.

  • 25.
    Spaak, J
    et al.
    Karolinska Institutet.
    Montmerle, S
    Karolinska Institutet.
    Sundblad, Patrik
    Karolinska Institutet.
    Linnarsson, D
    Karolinska Institutet.
    Long-term bed rest-induced reductions in stroke volume during rest and exercise: cardiac dysfunction vs. volume depletion2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 98, no 2, p. 648-654Article in journal (Refereed)
    Abstract [en]

    Long-term head-down-tilt bed rest (HDT) causes cardiovascular deconditioning, attributed to reflex dysfunctions, plasma volume reduction, or cardiac impairments. Our objective with the present study was to evaluate the functional importance and relative contribution of these during rest and exercise in supine and upright postures. We studied six subjects before (baseline), during [days 60 (D60) and 113 (D113)], and after [recovery days 0 (R0), 3 (R3), and 15 (R15)] 120 days of -6 degrees HDT. We determined cardiac output, stroke volume (SV), mean arterial pressure, and heart rate during rest and exercise in supine and upright postures. Cardiac output and SV decreased significantly in all four conditions, but the time courses differed for rest and exercise. Upright resting SV was decreased by 24 +/- 9% at D60 compared with baseline but had recovered already at R3. Supine exercise SV decreased more slowly (by 5 +/- 8% at D60 and by 18 +/- 4% at D113) and recovered more slowly after HDT termination. Steady-state mean arterial pressure showed no changes. Heart rate had increased by 18 +/- 4% at D60 and had recovered partially at R3. Our data indicate that long-term HDT causes both a rapid, preload-dependent reduction in SV, most evident during rest in the upright position, and a more slowly developing cardiac dysfunction, most evident during supine exercise. However, the ability to maintain blood pressure and to perform sustained low levels of dynamic exercise is not influenced by HDT.

  • 26.
    Sundblad, Patrik
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Orlov, O
    Angerer, O
    Larina, IM
    Cromwell, R
    Standardization of Bed Rest Studies in the Spaceflight Context.2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 121, no 1, p. 348-349Article in journal (Refereed)
  • 27.
    Sundblad, Patrik
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Prisk, G. Kim
    Something from nothing?: Space research without leaving the planet2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 8, p. 889-890Article in journal (Other academic)
  • 28.
    Sundblad, Patrik
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology. Department of Physiology and Pharmacology, Karolinska Institutet, Sweden .
    Spaak, J.
    Kaijser, L.
    Time courses of central hemodynamics during rapid changes in posture.2014In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 116, no 9, p. 1182-1188Article in journal (Refereed)
    Abstract [en]

    Changes in posture cause blood volume redistribution, affecting cardiac filling and stroke volume (SV). We hypothesized that the time courses of ventricular filling would differ between the right and left ventricle during a rapid (2 s) tilt and that changes in right ventricular filling pressure would be more swift because of the direct coupling to the systemic circulation. We further hypothesized that the transient imbalance between right and left ventricular filling pressure would influence left ventricular SV changes. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), left ventricular stroke volume, heart rate, and arterial pressure were recorded beat-by-beat during rapid tilts from supine to upright positions and back again, during rest and dynamic 100-W leg exercise. RAP changes had a faster time course than PCWP during down-tilts, both during rest and exercise (1 +/- 1 vs. 6 +/- 2 s and 2 +/- 2 vs. 6 +/- 2 s, respectively; P < 0.05). This discrepancy caused a transient decrease in the end-diastolic pressure difference between the right and left ventricle. The decreased pressure difference in diastole impeded left ventricular filling because of ventricular interdependence, causing SV to fall transiently. The mechanisms of ventricular interdependence were also involved in reverse during up-tilt, where SV was maintained for 2-3 s despite falling PCWP. Furthermore, the decrease in RAP during up-tilt in the resting condition was biphasic with an initial fast and a second slower component, which might suggest the effect of venous valves. This was not seen during dynamic leg exercise where blood pooling is prevented by the venous muscle pump.

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