Adaptation to 5 weeks of intermittent local vascular pressure increments; mechanisms to be considered in the development of primary hypertension?

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150 mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressure-distension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension.NEW & NOTEWORTHY Adaptive responses to arterial/arteriolar pressure elevation have typically been investigated in cross-sectional studies in hypertensive patients or in longitudinal studies in experimental animals. The present investigation shows that in healthy individuals, fifteen 40-min, carefully controlled, moderate transmural pressure elevations markedly increase in vivo stiffness (i.e. reduce pressure distension) in arteries and arterioles. The response is mediated via local mechanisms, and it appears that endothelin-1, angiotensin-II, and matrix metalloproteinase 7 may have key roles.

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); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °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 (-1.3 °C; P = 0.05). 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 (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) 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.

Peak oxygen uptake and regional oxygenation in response to a 10-day confinement to normobaric hypoxia.

We investigated the effect of hypoxic acclimatization per se, without any concomitant influence of strenuous physical activity on muscle and cerebral oxygenation. Eight healthy male subjects participated in a crossover-designed study. In random order, they conducted a 10-day normoxic (CON) and a 10-day hypoxic (EXP) confinement. Pre and post both CON and EXP confinements, subjects conducted two incremental-load cycling exercises to exhaustion; one under normoxic, and the other under hypoxic (F(I)O(2) = 0.154) conditions. Oxygen uptake (V˙O(2)), ventilation (V˙(E)), and relative changes in regional hemoglobin oxygenation (Δ([HbO(2)]) in the cerebral cortex and in the serratus anterior (SA) and vastus lateralis (VL) muscles were measured. No changes were observed in the CON confinement. Peak work rate and V˙O(2peak) were similar pre and post in the EXP confinement, whereas V˙(E) increased in the EXP post normoxic and hypoxic trials (P < 0.05). The exercise-induced drop in VL Δ[HbO(2)] was less in the post- than pre-EXP trial by 4.0 ± 0.4 and 4.2 ± 0.6 µM during normoxic and hypoxic exercise, respectively. No major changes were observed in cerebral or SA oxygenation. These results demonstrate that a 10-day hypoxic exposure without any concomitant physical activity had no effect on normoxic or hypoxic V˙O(2peak), despite the enhanced VL oxygenation.

PlanHab Study: Consequences of combined normobaric hypoxia and bed rest on adenosine kinetics.

Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions - together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.

Cutaneous exposure to hypoxia does not affect skin perfusion in humans.

AIM: Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O2 availability. Specifically, a reduction in skin-surface PO2 attenuates transcutaneous O2 diffusion, and hence epidermal O2 supply. In response, epidermal HIF-1α expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide-dependent vasodilation. Here, we investigated whether the same mechanism exists in humans. METHODS: In a first experiment, eight males rested twice for 8 h in a hypobaric chamber. Once, barometric pressure was reduced by 50%, while systemic oxygenation was preserved by O2 -enriched (42%) breathing gas (HypoxiaSkin ), and once barometric pressure and inspired O2 fraction were normal (Control1 ). In a second experiment, nine males rested for 8 h with both forearms wrapped in plastic bags. O2 was expelled from one bag by nitrogen flushing (AnoxiaSkin ), whereas the other bag was flushed with air (Control2 ). In both experiments, skin blood flux was assessed by laser Doppler on the dorsal forearm, and HIF-1α expression was determined by immunohistochemical staining in forearm skin biopsies. RESULTS: Skin blood flux during HypoxiaSkin and AnoxiaSkin remained similar to the corresponding Control trial (P = 0.67 and P = 0.81). Immunohistochemically stained epidermal HIF-1α was detected on 8.2 ± 6.1 and 5.3 ± 5.7% of the analysed area during HypoxiaSkin and Control1 (P = 0.30) and on 2.3 ± 1.8 and 2.4 ± 1.8% during AnoxiaSkin and Control2 (P = 0.90) respectively. CONCLUSION: Reductions in skin-surface PO2 do not affect skin perfusion in humans. The unchanged epidermal HIF-1α expression suggests that epidermal O2 homoeostasis was not disturbed by HypoxiaSkin /AnoxiaSkin , potentially due to compensatory increases in arterial O2 extraction.

Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths.

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.

Nitrogen narcosis attenuates shivering thermogenesis.

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.

Muscle oxidative capacity and work performance after training under local leg ischemia.

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.

Human skeletal muscle function and metabolism during intense exercise at high O2 and N2 pressures.

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.

Muscle control in elite alpine skiing.

PURPOSE: The purpose of this study was to determine whether muscle control may be influenced by accelerative forces brought about by the downhill displacement of body mass in combination with the sharp turns during alpine skiing. METHODS: Sixteen elite skiers performed either super G (SG), giant slalom (GS), slalom (SL), or freestyle mogul (FM) skiing. Knee and hip joint angles and electromyographic (EMG) activity of the knee extensors were recorded. RESULTS: During the course of a turn, the minimum (deepest stance position) knee angle of the outside (main load-bearing) leg ranged from 60 degrees to 100 degrees, where the smallest angle was obtained in the FM event. Among the traditional alpine disciplines, smaller knee angles were obtained in the high-speed events (i.e., knee angle: SG

Involvement of eccentric muscle actions in giant slalom racing.

Joint angular movements and muscle activation (EMG), were determined in male elite racers while performing the giant slalom. Movement cycles averaged 3.5 +/- 0.6 s (left plus right turn), and knee angle ranged 66-114 degrees (180 degrees = straight leg). Knee extensor muscle use was dominated (rectified EMG; P < 0.05) by the leg controlling the outside (downhill) ski during the turn. Time spent while decreasing knee angle (eccentric muscle action) of outside leg averaged 1.0 +/- 0.2 s. This phase was longer (P < 0.05) than the average push-off (concentric muscle action) phase of 0.5 +/- 0.1 s. Moreover, EMG activity of the outside leg during eccentric muscle actions exceeded (P < 0.05) that of concentric actions and was similar to that attained during maximum isometric knee extension in laboratory tests. Knee and hip angular movement ranged 20-50 degrees. Average joint velocities equalled 20-40 degrees.s(-1) during the turning phase. Thus, competitive giant slalom skiing is dominated by slow eccentric muscle actions performed at near maximum voluntary force. Because of their greater ability to generate force, eccentric muscle actions may be warranted or even required to resist the G-forces induced during the turn phase.

Hyperbaric oxygen therapy does not affect recovery from delayed onset muscle soreness.

PURPOSE: This study investigated whether hyperbaric oxygen therapy (HBOT) improves recovery after exercise-induced muscle injury. METHODS: Healthy male subjects (N = 24) were randomly assigned to either a placebo group or a HBOT group. Subjects were tested for maximal isometric strength (preexercise) of their right elbow flexors. Each subject then completed a high-force eccentric workout of the elbow flexor muscle group to induce delayed onset muscle soreness (DOMS). On the seven successive days after this workout, the subjects were exposed to a hyperbaric environment of 2.5 ATA for 60 min, inspiring either a normoxic mixture (P(I)O2 = 0.2 ATA; placebo group) or a hyperoxic gas mixture (P(I)O2 = 2.5 ATA; HBOT group). Before the eccentric workout and daily for the next 10 d, measurements were obtained regarding: maximal isometric muscle strength of the elbow flexor muscles, right upper arm circumferences, and rating of the perceived muscle soreness. RESULTS: Isometric strength decreased significantly from preexercise levels of 25.1 +/- 3.8 kp to postexercise levels of 12.0 +/- 4.6 kp, for the HBOT group, and from 24.6 +/- 3.4 kp to 12.5 +/- 3.7 kp, respectively, for the placebo group. Over the 10-d recovery period, there was no difference in the rate of recovery of muscle strength between the two groups. Perceived soreness peaked at about 48 h after exercise with no difference between groups. Also, the exercise-induced increases in arm circumference were similar in the two groups. CONCLUSIONS: These results indicate that HBOT is not an effective therapy for the treatment of DOMS.

Relation between the elastic properties and intima-media thickness of the common carotid artery.

The purpose of the study was to describe the relation between wall elasticity and intima-media thickness in the human carotid artery prior to the development of atherosclerotic plaques. Fifty-eight apparently healthy men, aged 42-65 years (mean 55 years), without symptoms of cardiovascular disease were studied. Thickness and elastic properties of the common carotid artery wall were assessed using ultrasonography and non-invasive arterial pressure measurements. The relation between the calculated intima-media area and the pressure strain elastic modulus was positive and statistically significant on the right but not on the left side. No statistically significant relations were found between the calculated intima-media area and the stiffness or between the intima-media thickness and the elastic modulus or stiffness on either side. Thus, the relations between the common carotid artery intima-media thickness/calculated intima-media area and the common carotid artery elastic modulus/stiffness are weak. In regions without atherosclerotic plaques, the elastic properties of the human carotid artery wall do not seem to be influenced by the wall thickness in an important way.

Relationship between arm pain and distension of arteries and veins caused by elevation of transmural pressure in local vascular segments.

BACKGROUND: Exposure to high +Gz forces may induce arm pain, which has been hypothesized to be caused by pressure-induced overdistension of local blood vessels. The purpose of the present investigation was to study the pressure-distension relation of veins and arteries in the human arm and the relation between arm pain and distension of local vessels. METHODS: Increased distending pressures (DP) in the vasculature of the arm were accomplished by placing the subject (n = 8) in a pressure chamber with one arm positioned through a port in the chamber door, and increasing chamber pressure to +180 mm Hg in a stepwise manner. Diameters in the brachial artery and in the brachial, radial and cephalic veins were measured by ultrasonography. Changes in forearm volume were estimated from measurement of tissue impedance. Perceived pain was rated using a 10-point scale. RESULTS: Arm pain increased with pressure to a maximum rating of 8.5 (= median; range: 4-10). Increasing DP from 30 to 180 mm Hg resulted in a steady increase (p < 0.05) in venous diameter which varied from 12 +/- 8% (mean +/- SD) in the brachial vein to 23 +/- 14% in the radial vein. Inthe brachial vein diameter increases were most pronounced at the sites of the venous valves. Arterial diameter was unchanged up to a DP of about 200 mm Hg (calculated as diastolic arterial pressure + applied chamber pressure), but then increased by 32 +/- 9% (p < 0.001). Forearm impedance dropped with increasing pressure (delta = 23 +/- 5%; p < 0.01); the rate of change was non-linear with a faster change at the highest DP which may indicate pressure distension of precapillary resistance vessels. CONCLUSIONS: Elevation of pressure in arm vessels to levels that may occur in pilots flying high-performance aircraft results in distension not only of veins but also of arteries and probably of smaller precapillary vessels. Therefore, and because these changes coincide with the development of severe arm pain, local overdistension of blood vessels remains a plausible cause of G-induced arm pain.

Inhalation rewarming from hypothermia: an evaluation in -20 degrees C simulated field conditions.

The present study evaluates the efficacy of inhaling warm moist air as a method of rewarming from hypothermia in -20 degrees C field conditions. The method of inhalation rewarming is compared to two other methods of rewarming: a) passive rewarming; and b) passive rewarming, with a respiratory heat exchanger designed to minimize respiratory heat loss. Eight male subjects were rendered hypothermic by immersion in 15 degrees C water for 1 h. They were withdrawn from the tank earlier, in the event that their rectal temperature (Tre) decreased to 35 degrees C, or by 1.5 degrees C from the pre-immersion value. Upon completion of the immersion, they were placed in a well-insulated sleeping bag assembly and transferred to a cold room maintained at -20 degrees C for a 2 h rewarming period. They participated in 3 trials: Control-passive rewarming; Heat Treat-inhalation rewarming with the Heat Treat; HME-passive rewarming in conjunction with a respiratory heat and moisture exchanger (HME). During the rewarming period, inspired air temperature was -19.4 +/- 1.1 degrees C in the control trial. In the HME and Heat Treat trials subjects breathed via an oro-nasal mask. The inspired air temperature was +20.5 +/- 1.2 degrees C in the HME and +36.2 +/- 2.9 degrees C in the Heat Treat trial. The post-immersion drop in Tre was significant in all conditions. The reduction in the post-exposure drop in Tre observed with the Heat Treat may be attributed to the minimization of respiratory heat loss, since the magnitude of the reduction was similar to that observed with the HME.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of straining maneuvers on G-protection during assisted pressure breathing.

INTRODUCTION: Pilots flying high-performance aircraft increase their acceleration tolerance by using straining maneuvers and anti-G suits. Recently, assisted positive pressure breathing has been added in some aircraft systems. This study assessed the effect of anti-G straining maneuvers on the G-protective properties of one such system, the AGE-39 anti-G ensemble used in the Swedish JAS 39 Gripen aircraft. METHODS: Ten subjects were studied in a centrifuge using each of the following: 1) the AGE-39 in combination with anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); 2) the AGE-39 in combination with AGSM only during the initial part of each high-G exposure (reduced maneuver; RM). G-tolerance was established during exposures to rapid onset rate (ROR) G profiles with plateau levels ranging from 6.5 to 9.0 G. RESULTS: Mean G-tolerance was > or = 8.8 G (range: 8.5 to > or = 9.0 G) in the RM condition and > or = 9.0 G in all subjects in the FM condition. Mean arterial pressure was 30-50 mm Hg higher (p < 0.001) in the FM than in the RM condition at any given ROR G-load. CONCLUSIONS: AGE-39 in combination with a brief period of straining provide efficient G-protection as illustrated by the finding that all subjects could tolerate 8.5 G while performing AGSM during the initial part of the high-G exposures. However, at 9.0 G, 40% of the subjects had to perform AGSM throughout the duration of the G-exposure. That arterial pressure was only 30-50 mm Hg higher in the FM than RM condition suggests that in the presence of straining maneuvers, pressure breathing makes only a minute contribution to the arterial-pressure response.

A new hydrostatic anti-G suit vs. a pneumatic anti-G system: preliminary comparison.

HYPOTHESIS: A newly developed hydrostatic anti-G suit is now commercially available. The suit is said to offer a high level of protection against +Gz acceleration. However, past experience shows that it is difficult to produce a hydrostatic suit with effective high-G protection. Careful testing is, therefore, needed to verify its efficacy. METHODS: The G-protective properties of the hydrostatic anti-G suit (Libelle; L) were compared with those of a pneumatic anti-G ensemble (AGE-39) used in the Swedish JAS 39 Cripen aircraft. Three pilots were studied during vertical (+Gz) acceleration in a centrifuge using the following: 1) the L-suit with varied straining maneuvers; 2) the AGE-39 in combination with full anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); and 3) the AGE-39 in combination with AGSM during the initial part of each high-G exposure (reduced maneuver; RM). G-intensity tolerance was established during exposures to rapid onset rate (ROR) profiles with G-plateau levels ranging from +6.0 to +9.0 Gz. G-endurance was studied during simulated aerial combat maneuvers (SACM) consisting of 10 cycles of 5.5 to 7.5 G. RESULTS: All three pilots tolerated 9.0 G with the pneumatic system both in the RM and FM conditions; their tolerances averaged 6.3 G (range 6.0 to 7.0 G) for the L suit. Thus, during the ROR exposures only the 6.0 G profile was completed by all subjects in all three conditions. At this G-load both muscle straining (as indicated by electromyographic activity in thigh and abdomen) and heart rate were higher in the L than in the RM condition. Mean arterial pressure at eye level was higher in the FM than in the L and RM conditions. Only one subject was able to complete the SACM profile in the L condition. In the RM condition all subjects completed the SACM profile and in the FM condition two subjects completed the SACM. CONCLUSIONS: Whether the AGE-39 was used in combination with maximal AGSM throughout the duration of each high-G exposure or with AGSM only during the initial part of the high-G exposure, G-intensity tolerance was 9.0 G. While wearing the L-suit, G-tolerance was 6.3 G. Thus, under the conditions tested, the G-protection afforded by the L-suit is not adequate for use in a 9-G aircraft.

Perception of thermal comfort during narcosis.

We examined the perception of thermal comfort in six male subjects immersed in water at 28 degrees C (study I) and 15 degrees C (study II), breathing either room air (AIR) or a normoxic mixture containing 30% N2O (N2O). Immersions were terminated if esophageal temperature (Tes) decreased by 2 degrees C from resting levels or to 35 degrees C. At regular intervals, subjects rated their perception of thermal comfort on a 21-point scale (thermal comfort vote, TCV; +10 = very, very hot, 0 = neutral, -10 = very, very cold). For similar decreases in Tes from resting preimmersion values (mean +/- SD = -0.90 degrees +/- 0.13 degrees C and -0.92 degrees +/- 0.15 degrees C during the AIR and N2O trials in study I, and -0.90 degree +/- 0.22 degree C and -0.89 degree +/- 0.27 degree C during the AIR and N2O trials in study II), subjects perceived the immersions as less cold during the N2O trials. The median TCVs for the AIR condition of -5 in study I and -7.75 in study II, were significantly lower than those reported by the subjects for the respective N2O conditions (1.75 in study I and -5.5 in study II). It is concluded that behavioral adjustments required for maintaining thermal balance may be diminished during narcosis due to the altered perception of thermal discomfort. Assuming that the effect of inert gas narcosis on thermoregulatory responses is similar to that of N2O, then combined with the significant attenuation of heat gain mechanisms by anesthetic gases, the attenuation of the perception of thermal comfort may represent a significant factor in the etiology of hypothermia observed in compressed air divers.

Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males.

AIM: Studies in humans show global changes in mRNA and protein expression occur in human skeletal muscle during bed rest. As microRNAs are important regulators of expression, we analysed the global microRNA expression changes in human muscle following 10 days of sustained bed rest, with the rationale that miRNAs play key roles in atrophy of skeletal muscle. METHODS: We analysed expression of miRNA and selected target proteins before and after 10 days of bed rest in biopsies obtained from the vastus lateralis muscle of 6 healthy males. RESULTS: Fifteen of 152 miRNAs detected in human muscle tissue were differentially expressed, and all of them with exception of two were downregulated. The downregulated miRNAs include the following: miR-206, a myomir involved in function and maintenance of skeletal muscle; miR-23a, involved in insulin response and atrophy defence; and several members of the let-7 family involved in cell cycle, cell differentiation and glucose homeostasis. Predicted gene targets of these miRNAs are members of the MAPK, TNF receptor, ALK1, TGF-beta receptor and SMAD signalling pathways. All of these pathways were previously indicated to be involved in skeletal muscle response to physical inactivity. We also measured protein expression of selected miRNA targets and observed a decrease in HDAC4. CONCLUSION: Our data demonstrate that miRNAs in postural muscles are affected by sustained inactivity and unloading, as induced by prolonged bed rest, and hence are potentially involved in regulation of skeletal muscle adjustments to inactivity. We also propose new miRNAs involved in regulation of biological processes in adult human muscle.

Elevations of local intravascular pressures release vasoactive substances in humans.

The wall stiffness of arteries and arterioles adapts to the long-term demands imposed by local intravascular pressure. We investigated whether substances capable of inducing acute and long-term effects on arterial wall stiffness are released locally into the bloodstream in response to an acute marked increase in local intravascular pressure in the blood vessels of the human arm. Experiments were performed on ten subjects positioned in a pressure chamber with one arm extended through a hole in the chamber door and kept at normal atmospheric pressure. Intravascular pressure was increased in the arm, by a stepwise increase in chamber pressure up to +150 mmHg. Diameter and flow were measured in the brachial artery by Doppler ultrasonography. Blood samples were drawn simultaneously from both arms before, during, immediately after and 2 h after the release of the chamber pressure. Plasma levels of endothelin-1 (ET-1), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and angiotensin II (Ang-II) were measured. Elevation of chamber pressure by 150 mmHg increased local arterial distending pressure to about 220-260 mmHg, resulting in an increase in brachial artery diameter of 9% and flow of 246%. The pressure stimulus increased the plasma levels of ET-1 and Ang-II, but not of VEGF-A or FGF-2 in the test arm. The local release of the vasoconstrictors ET-1 and Ang-II in response to markedly increased distending pressure may reflect one mechanism behind adaptation to acute and long-term changes in intravascular pressure.