In pursuit of the unicorn.

This short review was prompted by The Physiological Society's recent online symposium on variability. It does not deal with a specific methodology, but rather with the myth that certain environmentally-induced clinical conditions can be identified, quantified, simplified and monitored with a single methodology. Although this might be possible with some clinical conditions, others resist the prevailing reductionist approach of minimizing rather than exploring variation in pathogenesis and pathology, and will not be understood fully until the variation in cause and effect are embraced. This is likely to require comprehensive methodologies and collaboration.

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.

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.

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.

Moderate hypoxia does not affect the zone of thermal comfort in humans.

The zone of thermal comfort was determined during normoxia and hypoxia in 15 healthy normothermic young subjects. Subjects dressed only in shorts/shorts and bikini top donned a water-perfused suit and assumed a supine position on a bench. The ambient temperature was maintained at a mean (SD) of 25.7 (0.3) degrees C. The thermal comfort zone was determined by increasing the temperature of the water perfusing the suit from cool to warm. During the heating process, subjects were instructed to report when their perception of the thermal stimulus provided by the suit changed from unpleasant to pleasant, and again from pleasant to unpleasant. The boundaries of the thermal comfort zone were assumed to be the temperatures of the water perfusing the suit at the time the subjects reported a change in the affective component of their thermal perception. In normoxia, subjects inspired room air and in hypoxia a gas mixture containing 10% O(2) in N(2). Tympanic temperature was similar in the normoxia and hypoxia conditions (P>0.05). The average (SD) lower and upper limits of the thermal comfort zone were 30.5 (1.5) and 34.7 (3.3) degrees C, respectively, during normoxia, and 30.5 (1.7) and 35.1 (3.4) degrees C, respectively, during hypoxia. No significant differences were observed between the normoxia and hypoxia conditions (P>0.05). Also, no gender-related differences were observed in the characteristics of the thermal comfort zone. The results of the present study indicate that acute hypoxic exposure simulated in the present study does not affect the zone of thermal comfort in humans.

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.

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.

Permanence of the habituation of the initial responses to cold-water immersion in humans.

Sudden immersion in cold water initiates an inspiratory gasp response followed by uncontrollable hyperventilation and tachycardia. It is known that this response, termed the "cold shock" response, can be attenuated following repeated immersion. In the present investigation we examined how long this habituation lasts. Twelve healthy male volunteers participated in the experiment, they were divided into a control (C) group (n = 4), and a habituation (H) group (n = 8). In October, each subject undertook two 3-min head-out seated immersions into stirred water at 10 degrees C wearing swimming trunks. These immersions took place at the same time of day, with 4 days separating the two immersions. In the intervening period, the C group were not exposed to cold water, while the H group undertook six, 3-min head-out immersions in water at 15 degrees C. Two months (December), 4 months (February), 7 months (May) and 14 months (January) after their first immersion, all subjects undertook another 3-min head-out immersion in water at 10 degrees C. The H group showed a reduction in respiratory frequency (47 to 24 breaths x min(-1)), inspiratory minute volume (72.2 to 31.3 1 x min(-1)) and heart rate (128 to 109 beats x min(-1)) during the first 30 s of immersion on day 5 compared to day 1. Seven months later these responses were still significantly reduced compared to day 1. After 14 months, heart rate remained attenuated but respiratory frequency and inspiratory minute volume had returned towards pre-habituation levels. The responses of the C group during the first 30 s of immersion were not altered. Both groups showed an attenuation in the responses during the remaining 150 s of immersion following repeated immersions. It is concluded that repeated immersions in cold water result in a longlasting (7-14 months) reduction in the magnitude of the cold shock response. Less frequent immersions produced a decrease in the duration, but not the magnitude of the response.

The effect of nitrous oxide-induced narcosis on aerobic work performance.

Previous findings of a narcosis-induced reduction in heat production during cold water immersion, as reflected in oxygen uptake (VO2), have been attributed to the attenuation of the shivering response. The possibility of reduced oxygen utilization (VO2) by the muscles could not, however, be excluded. Accordingly, the present study tested the hypothesis that mild narcosis, induced by inhalation of a normoxic gas mixture containing 30% nitrous oxide (N2O), would affect VO2. Nine male subjects participated in both maximal and submaximal exercise trials, inspiring either room air (AIR) or a normoxic mixture containing 30% N2O. In the submaximal trials, the subjects exercised at 50% of maximal exercise intensity (Wmax) as determined in the maximal AIR trial. Though the subjects attained the same Wmax in the AIR and N2O trials, maximal VO2 was significantly higher (P < 0.05) during the N2O condition [58.9 (SEM 3.1) ml x kg(-1) x min(-1)] compared to the AIR condition [55.0 (SEM 2.4) ml x kg(-1) x min(-1)]. However, the VO2-relative exercise intensity relationship was similar during both maximal AIR and maximal N2O at submaximal exercise intensities. There were no significant differences in the responses of oesophageal temperature, sweating rate, heart rate and ventilation between AIR and N2O in the maximal and submaximal tests. It was concluded that the previously reported narcosis-induced reductions in VO2 observed during cold water immersion can be attributed solely to a reduction in the shivering response rather than to decreased oxygen utilization by the muscles.

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.

Temperature dependence of habituation of the initial responses to cold-water immersion.

The initial responses to cold-water immersion, evoked by stimulation of peripheral cold receptors, include tachycardia, a reflex inspiratory gasp and uncontrollable hyperventilation. When immersed naked, the maximum responses are initiated in water at 10 degrees C, with smaller responses being observed following immersion in water at 15 degrees C. Habituation of the initial responses can be achieved following repeated immersions, but the specificity of this response with regard to water temperature is not known. Thirteen healthy male volunteers were divided into a control (C) group (n = 5) and a habituation (H) group (n = 8). Each subject undertook two 3-min head-out immersions in water at 10 degrees C wearing swimming trunks. These immersions took place at a corresponding time of day with 4 days separating the two immersions. In the intervening period the C group were not exposed to cold water, while the H group undertook another six, 3-min, head-out immersions in water at 15 degrees C. Respiratory rate (fR), inspiratory minute volume (VI) and heart rate (fH) were measured continuously throughout each immersion. Following repeated immersions in water at 15 degrees C, the fR, VI and fH responses of the H group over the first 30 s of immersion were reduced (P < 0.01) from 33.3 breaths x min(-1), 50.5 l x min(-1) and 114 beats x min(-1) respectively, to 19.8 breaths x min(-1) 26.41 x min(-1) and 98 beats x min(-1), respectively. In water at 10 degrees C these responses were reduced (P < 0.01) from 47.3 breaths x min(-1), 67.61 x min(-1) and 128 beats x min(-1) to 24.0 breaths x min(-1), 29.5 l x min(-1) and 109 beats x min(-1), respectively over a corresponding period of immersion. Similar reductions were observed during the last 2.5 min of immersions. The initial responses of the C group were unchanged. It is concluded that habituation of the cold shock response can be achieved by immersion in warmer water than that for which protection is required. This suggests that repeated submaximal stimulation of the cutaneous cold receptors is sufficient to attenuate the responses to more maximal stimulation.

Ocular bubble formation as a method of assessing decompression stress.

Tear film bubble formation and ultrasound reflectivity of the lens-vitreous humor compartments were monitored following simulated dives in a hyperbaric chamber. the sensitivity of these methods in determining decompression stress was compared with the results of precordial Doppler ultrasound. In addition, the utility of these diagnostic techniques in testing decompression dive profiles was evaluated. Eleven divers completed two series of chamber dives according to the decompression schedule of the Professional Association of Diving Instructors. The first dive series comprised dives to 70 feet of seawater (fsw) for 15, 29, and 40 min. The second series comprised maximum duration no-stop decompression dives to 40 fsw for 140 min, 70 fsw for 40 min, 90 fsw for 25 min, and 120 fsw for 13 min. Before and immediately after each dive, the following measurements were obtained from each subject: eye surface tear film bubble counts with a slit-lamp microscope, lens and vitreous humor reflectivity using A- and B-mode ophthalmic ultrasonic scan, and precordial Doppler ultrasonic detection of venous gas bubbles. Tear film bubble assessment and ocular scanning ultrasound were observed to be more sensitive in detecting decompression stress than the conventional Doppler ultrasonic surveillance of the precordial region. In contrast to precordial Doppler ultrasonic surveillance, which failed to detect any significant changes in circulating bubbles, tear film bubble formation displayed a dose-response relationship with increasing duration of the 70-fsw dives. Reflectivity changes of the lens-vitreous humor interface were not significant until the no-stop decompression limit was reached. In addition, for each of the no-stop decompression limit dives, increases in the average tear film bubble formation and lens-vitreous humor interface reflectivity were similar. Ocular bubble observations may provide a practical and objective ocular bubble index for analyzing existing decompression schedules and predicting individual susceptibility to decompression sickness.

Substrate utilisation during exercise and shivering.

It is generally assumed that exercise and shivering are analogous processes with regard to substrate utilisation and that, as a consequence, exercise can be used as a model for shivering. In the present study, substrate utilisation during exercise and shivering at the same oxygen consumption (VO2) were compared. Following an overnight fast, eight male subjects undertook a 2-h immersion in cold water, designed to evoke three different intensities of shivering. At least 1 week later they undertook a 2-h period of bicycle ergometry during which the exercise intensity was varied to match the VO2 recorded during shivering. During both activities hepatic glucose output (HGO), the rate of glucose utilisation (Rd), blood glucose, plasma insulin, free fatty acid (FFA) and beta-hydroxybutyrate (B-HBA) concentrations were measured. The VO2 measured during the different levels of shivering averaged 0.49 l.min-1 (level 1: low), 0.6 l.min-1 (level 2: low-moderate), and 0.9 l.min-1 (level 3: moderate), and corresponded closely to the levels measured during exercise. HGO and Rd were greater (P < 0.05) during exercise than during shivering at the same VO2 (9.5% and 14.7%, respectively). The average (SD). HGO during level 3 exercise was 3.0 (0.91) mg.kg-1.min-1 compared to 2.76 (1.0) mg.kg-1.min-1 during shivering. The values for Rd were 3.06 (0.98) mg.kg-1.min-1 during level 3 exercise and 2.68 (0.82) mg.kg-1.min-1 during shivering. Blood glucose levels did not differ between conditions averaging 5.4 (0.3) mmol.l-1 over all levels of shivering and 5.2 (0.3) mmol.l-1 during exercise. Plasma FFA and B-HBA were higher (P < 0.01) during shivering than during corresponding exercise (12.3% and 33.3%, respectively). FFA averaged 0.61 (0.2) mmol.l-1 over all levels of shivering and 0.47 (0.16) mmol.l-1 during exercise. The figures for L-HBA were 0.44 (0.13) mmol. l-1 during all levels of shivering and 0.32 (0.1) mmol.l-1 during exercise. Plasma insulin was higher (P < 0.05) during level 2 and 3 shivering compared to corresponding exercise; at these levels the average value for plasma insulin was 95.9 (21.9) pmol.l-1 during shivering and 80.6 (16.1) pmol.l-1 during exercise. On the basis of the present findings it is concluded that, with regard to substrate utilisation, shivering and exercise of up to 2 h duration should not be regarded as analogous processes.

Effect of hypoglycemia on thermoregulatory responses.

The effects of hypoglycemia on sweating, skin blood perfusion, and shivering responses were investigated in 10 healthy male volunteers. They exercised on an underwater cycle ergometer while immersed to the neck in 28 degrees C water for 20 min at 50% of their maximal work rate. The exercise-induced elevation in esophageal temperature (T(es)) initiated the sweating response (Esw) and increased skin blood perfusion (SkBP) as measured at the forehead. In the 99-min postexercise immersion period, the values of T es relative to resting level (delta T(es)) at which Esw abated, SkBP reached preexercise values, and shivering commenced were defined as the delta T(es) thresholds for cessation of sweating, passive vasodilation, and onset of shivering, respectively. Two trials were conducted 1 wk apart. The subject was hypoglycemic in one trial and euglycemic in the other (plasma glucose was maintained at 2.8 and 5 mM, respectively) with the use of the hyperinsulinemic (insulin infusion rate = 60 mU.m-2.min-1) glucose-clamp technique. Oxygen uptake, Esw, T(es), mean skin temperature, heat flux from the skin, and SkBP were recorded at minute intervals. Although heat flux and SkBP attained significantly higher end-exercise levels during euglycemia, the responses were similar during the postexercise cooling period. Hypoglycemia did not affect the Esw response during the exercise and cooling periods. Whereas the exercise delta T(es) response was unaffected by hypoglycemia, the decrease in T(es) was greater (P < or = 0.005) during the hypoglycemic than during the euglycemic condition. Hypoglycemia did not alter the delta T(es) threshold for cessation of sweating and passive vasodilation but reduced (P < or = 0.001) the delta T(es) threshold for onset of shivering (from -0.09 +/- 0.07 degrees C in the euglycemic condition to -0.65 +/- 0.12 degrees C in the hypoglycemic condition). The present results indicate that hypoglycemia (2.8 mM) does not affect the delta T(es) threshold for cessation of thermoregulatory sweating or the threshold for passive vasodilation during recovery from exercise-induced moderate heat stress but that it decreases the core temperature threshold for shivering during cold exposure.