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.

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.

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.

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.

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.

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.

Carbon monoxide exposure during exercise performance: muscle and cerebral oxygenation.

AIM: To investigate the effect of carbon monoxide (CO) in the inspired air as anticipated during peak hours of traffic in polluted megalopolises on cerebral, respiratory and leg muscle oxygenation during a constant-power test (CPT). In addition, since O(2) breathing is used to hasten elimination of CO from the blood, we examined the effect of breathing O(2) following exposure to CO on cerebral and muscle oxygenation during a subsequent exercise test under CO conditions. METHODS: Nine men participated in three trials: (i) 3-h air exposure followed by a control CPT, (ii) 1-h air and 2-h CO (18.9 ppm) exposure succeeded by a CPT under CO conditions (CPT(COA)), and (iii) 2-h CO and 1-h 100% normobaric O(2) exposure followed by a CPT under CO conditions (CPT(COB)). All exercise tests were performed at 85% of peak power output to exhaustion. Oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total (Δ[tHb]) haemoglobin in cerebral, intercostal and vastus lateralis muscles were monitored with near-infrared spectroscopy throughout the CPTs. RESULTS: Performance time did not vary between trials. However, the vastus lateralis and intercostal Δ[O(2)Hb] and Δ[tHb] were lower in CPT(COA) than in CPT. During the CPT(COB), the intercostal Δ[O(2) Hb] and Δ[tHb] were higher than in the CPT(COA). There were no differences in cerebral oxygenation between the trials. CONCLUSION: Inspiration of 18.9 ppm CO decreases oxygenation in the vastus lateralis and serratus anterior muscles, but does not affect performance. Breathing normobaric O(2) moderates the CO-induced reductions in muscle oxygenation, mainly in the intercostals, but does not affect endurance.

Acute normobaric hyperoxia transiently attenuates plasma erythropoietin concentration in healthy males: evidence against the 'normobaric oxygen paradox' theory.

AIM: The purpose of the present study was to evaluate the 'normobaric oxygen paradox' theory by investigating the effect of a 2-h normobaric O(2) exposure on the concentration of plasma erythropoietin (EPO). METHODS: Ten healthy males were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O(2) (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration. RESULTS: The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P ≤ 0.05) as a consequence of its natural diurnal variation. Conversely, the O(2) breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P ≤ 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the breathing intervention (P ≤ 0.05). CONCLUSION: In contrast to the 'normobaric oxygen paradox' theory, the present results indicate that a short period of normobaric O(2) breathing does not increase the EPO concentration in aerobically fit healthy males. Increased O(2) tension suppresses the EPO concentration 3 and 5 h after the exposure; thereafter EPO seems to change in a manner consistent with natural diurnal variation.

Effects of anti-histaminic and anti-cholinergic substances on human thermoregulation during cold provocation.

The roles of histaminergic and cholinergic neuron systems in the regulation of body temperature have been studied almost exclusively in animals. Recently, we have found that motion sickness, i.e. a condition where hippocampal cholinergic mismatch signals induce a release of histamine in the vomiting centre, accelerates the decline in body temperature in men during exposure to cold. In the present study we measured the thermoregulatory effects of two substances commonly used against motion sickness, i.e. the histamine (H1) receptor blocker dimenhydrinate (DMH) and the muscarine receptor blocker scopolamine (SCOP). In three trials, control (CN), DMH and SCOP, 10 male subjects were immersed in 15 degrees C water for a maximum of 90 min. The trials were separated by a minimum of three days and their order was alternated between subjects. In all trials the subject received, in a double blind fashion, a transdermal patch (SCOP or placebo) 12-14 h before immersion and a tablet (DMH or placebo) 1h before immersion. Mean skin temperature, rectal temperature (T(rec)), the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (T(ff)), and oxygen uptake (VO(2)) were recorded. The fall in T(rec) was smaller in the DMH than in the CN and SCOP conditions. The recordings of T(ff) and VO(2) suggest that SCOP attenuates peripheral vasoconstriction while DMH increases shivering thermogenesis. Notably, thermal discomfort was reduced in the SCOP condition. Findings are thoroughly discussed in the context of animal studies on the neuropharmacology and neurophysiology of thermoregulation and motion sickness.

Comparison of vascular distensibility in the upper and lower extremity.

AIM: Because of the great differences in hydrostatic pressure acting along the blood vessels in the erect posture, leg vessels are exposed to greater transmural pressures than arm vessels. The in vivo pressure-distension relationship of arteries, arterioles and veins in the arm were compared with those of the leg. METHODS: Experiments were performed with the subject (n = 11) positioned in a pressure chamber with an arm or lower leg (test limb) extended at heart level through a hole in the chamber door. Intravascular pressure in the arm/lower leg was increased by stepwise increasing chamber pressure to +180 and +210 mmHg, respectively. Diameters of blood vessels and arterial flow were measured using ultrasonographic/Doppler techniques. Changes in forearm and lower leg volumes were assessed using an impedance technique. The subject rated perceived pain in the test limb. RESULTS: The brachial and radial arteries were found to be more distensible than the posterior tibial artery (P < 0.001). Likewise, the distension was more pronounced in the cephalic than in the great saphenous vein (P < 0.001). In the brachial artery, but not in the posterior tibial artery, flow increased markedly at the highest levels of distending pressure (P < 0.001). At the highest intravascular pressures, the rate of change in tissue impedance was greater in the forearm than the lower leg (P < 0.01). At any given level of markedly increased pressure, pain was rated higher in the arm than in the leg (P < 0.001). CONCLUSION: It seems that the wall stiffness of arteries, pre-capillary resistance vessels and veins adapts to meet the long-term demands imposed by the hydrostatic pressure acting locally on the vessel walls.

Ischaemia in working muscles potentiates the exercise-induced sweating response in man.

AIM: The purpose was to examine whether graded ischaemia in the working muscles affects the rate of sweating and the control of exercise core temperature. METHODS: Eight subjects performed cycle ergometry exercise in the supine position with (ischaemic exercise) and without (control exercise) restriction of blood flow in the contracting muscles, accomplished by exposure of the legs to a supra-atmospheric pressure of 6.6 kPa. Each subject performed one exhaustive incremental work rate trial and one steady-state exercise trial (at 33% of control peak work rate), in both the control and ischaemia conditions. RESULTS: Ischaemia decreased work performance by 45% so that in this condition the steady-state work rate level corresponded to 63% of ischaemic peak work rate. Ischaemia did not affect the oesophageal temperature equilibrium in the steady-state trials, but potentiated the exercise sweating response. Exercise responses of mean arterial pressure, heart rate and pulmonary ventilation were potentiated by ischaemia. CONCLUSION: During ischaemic exercise sweat secretion was potentiated by non-thermal and/or local thermal stimuli.

Hypoxia increases the cutaneous threshold for the sensation of cold.

Cutaneous temperature sensitivity was tested in 13 male subjects prior to, during and after they breathed either a hypocapnic hypoxic (HH), or a normocapnic hypoxic (NH) breathing mixture containing 10% oxygen in nitrogen. Normocapnia was maintained by adding carbon dioxide to the inspired gas mixture. Cutaneous thresholds for thermal sensation were determined by a thermosensitivity testing device positioned on the plantar side of the first two toes on one leg. Heart rate, haemoglobin saturation, skin temperature at four sites (arm, chest, thigh, calf) and adapting temperature of the skin (T(ad); degrees centigrade), i.e. the temperature of the toe skin preceding a thermosensitivity test, were measured at minute intervals. Tympanic temperature (T(ty); degrees centigrade) was measured prior to the initial normoxic thermosensitivity test, during the hypoxic exposure and after the completion of the final normoxic thermosensitivity test. End-tidal carbon dioxide fraction and minute inspiratory volume were measured continuously during the hypoxic exposure. Ambient temperature, T(ty), T(ad) and mean skin temperature remained similar in both experimental conditions. Cutaneous sensitivity to cold decreased during both HH (P<0.001) and NH conditions (P<0.001) as compared with the tests undertaken pre- and post-hypoxia. No similar effect was observed for cutaneous sensitivity to warmth. The results of the present study suggest that sensitivity to cold decreases during the hypoxic exposure due to the effects associated with hypoxia rather than hypocapnia. Such alteration in thermal perception may affect the individual's perception of thermal comfort and consequently attenuate thermoregulatory behaviour during cold exposure at altitude.

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.

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.

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.

Motion sickness potentiates core cooling during immersion in humans.

1. The present study tested the hypothesis that motion sickness affects thermoregulatory responses to cooling in humans. 2. Ten healthy male volunteers underwent three separate head-out immersions in 28 degrees C water after different preparatory procedures. In the 'control' procedure immersion was preceded by a rest period. In the 'motion sickness' procedure immersion was preceded by provocation of motion sickness in a human centrifuge. This comprised rapid and repeated alterations of the gravitational (G-) stress in the head-to-foot direction, plus a standardized regimen of head movements at increased G-stress. In the 'G-control' procedure, the subjects were exposed to similar G-stress, but without the motion sickness provocation. 3. During immersion mean skin temperature, rectal temperature, the difference in temperature between the forearm and 3rd digit of the right hand (DeltaT(forearm-fingertip)), oxygen uptake and heart rate were recorded. Subjects provided ratings of temperature perception, thermal comfort and level of motion sickness discomfort at regular intervals. 4. No differences were observed in any of the variables between control and G-control procedures. In the motion sickness procedure, the DeltaT(forearm-fingertip) response was significantly attenuated, indicating a blunted vasoconstrictor response, and rectal temperature decreased at a faster rate. No other differences were observed. 5. Motion sickness attenuates the vasoconstrictor response to skin and core cooling, thereby enhancing heat loss and the magnitude of the fall in deep body temperature. Motion sickness may predispose individuals to hypothermia, and have significant implications for survival time in maritime accidents.

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.

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.