Toenail onychomycosis: an important global disease burden.

Onychomycosis is a fungal infection of the nail plate or nail bed. It does not usually cure itself and it can trigger more infectious lesions in other parts of the body. The reported prevalence of onychomycosis is increasing in Western countries, presumably due to lifestyle changes and the ageing of the population. Approximately 10% of the general population, 20% of the population aged>60 years, up to 50% of people aged>70 years and up to one-third of diabetic individuals have onychomycosis. Care should be taken for the accurate diagnosis and timely treatment of toenail onychomycosis to prevent complications. Current treatment options have relatively limited therapeutic success, particularly long-term. Oral medications are associated with high recurrence rates and treatment failure, and are not suitable for many cases due to potential adverse effects. Topical medications are recommended only for mild to moderate cases. The cost of therapies may also be prohibitive in some cases. In the light of these issues, more research is warranted for the investigation and development of more effective and economical options for the treatment and prophylaxis of toenail onychomycosis. In patient populations such as diabetic individuals, where onychomycosis can provoke lower extremity complications, professional podiatry care of toenails and feet should be encouraged.

Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythm.

Although a normal respiratory rhythm is vital at birth, little is known about the genetic factors controlling the prenatal maturation of the respiratory network in mammals. In Phox2a mutant mice, which do not express A6 neurons, we previously hypothesized that the release of endogenous norepinephrine by A6 neurons is required for a normal respiratory rhythm to occur at birth. Here we investigated the role of the Ret gene, which encodes a transmembrane tyrosine kinase receptor, in the maturation of norepinephrine and respiratory systems. As Ret-null mutants (Ret-/-) did not survive after birth, our experiments were performed in wild-type (wt) and Ret-/- fetuses exteriorized from pregnant heterozygous mice at gestational day 18. First, in wt fetuses, quantitative in situ hybridization revealed high levels of Ret transcripts in the pontine A5 and A6 areas. Second, in Ret-/- fetuses, high-pressure liquid chromatography showed significantly reduced norepinephrine contents in the pons but not the medulla. Third, tyrosine hydroxylase immunocytochemistry revealed a significantly reduced number of pontine A5 and A6 neurons but not medullary norepinephrine neurons in Ret-/- fetuses. Finally, electrophysiological and pharmacological experiments performed on brainstem 'en bloc' preparations demonstrated impaired resting respiratory activity and abnormal responses to central hypoxia and norepinephrine application in Ret-/- fetuses. To conclude, our results show that Ret gene contributes to the prenatal maturation of A6 and A5 neurons and respiratory system. They support the hypothesis that the normal maturation of the respiratory network requires afferent activity corresponding to the A6 excitatory and A5 inhibitory input balance.

Phox2a gene, A6 neurons, and noradrenaline are essential for development of normal respiratory rhythm in mice.

Although respiration is vital to the survival of all mammals from the moment of birth, little is known about the genetic factors controlling the prenatal maturation of this physiological process. Here we investigated the role of the Phox2a gene that encodes for a homeodomain protein involved in the generation of noradrenergic A6 neurons in the maturation of the respiratory network. First, comparisons of the respiratory activity of fetuses delivered surgically from heterozygous Phox2a pregnant mice on gestational day 18 showed that the mutants had impaired in vivo ventilation, in vitro respiratory-like activity, and in vitro respiratory responses to central hypoxia and noradrenaline. Second, pharmacological studies on wild-type neonates showed that endogenous noradrenaline released from pontine A6 neurons potentiates rhythmic respiratory activity via alpha1 medullary adrenoceptors. Third, transynaptic tracing experiments in which rabies virus was injected into the diaphragm confirmed that A6 neurons were connected to the neonatal respiratory network. Fourth, blocking the alpha1 adrenoceptors in wild-type dams during late gestation with daily injections of the alpha1 adrenoceptor antagonist prazosin induced in vivo and in vitro neonatal respiratory deficits similar to those observed in Phox2a mutants. These results suggest that noradrenaline, A6 neurons, and the Phox2a gene, which is crucial for the generation of A6 neurons, are essential for development of normal respiratory rhythm in neonatal mice. Metabolic noradrenaline disorders occurring during gestation therefore may induce neonatal respiratory deficits, in agreement with the catecholamine anomalies reported in victims of sudden infant death syndrome.

Ascent rate, age, maximal oxygen uptake, adiposity, and circulating venous bubbles after diving.

Decompression sickness in diving is recognized as a multifactorial phenomenon, depending on several factors, such as decompression rate and individual susceptibility. The Doppler ultrasonic detection of circulating venous bubbles after diving is considered a useful index for the safety of decompression because of the relationship between bubbles and decompression sickness risk. The aim of this study was to assess the effects of ascent rate, age, maximal oxygen uptake (VO(2 max)), and percent body fat on the production of bubbles after diving. Fifty male recreational divers performed two dives at 35 m during 25 min and then ascended in one case at 9 m/min and in the other case at 17 m/min. They performed the same decompression stops in the two cases. Twenty-eight divers were Doppler monitored at 10-min intervals, until 60 min after surfacing, and the data were analyzed by Wilcoxon signed-rank test to compare the effect of ascent rate on the kinetics of bubbles. Twenty-two divers were monitored 60 min after surfacing. The effect on bubble production 60 min after surfacing of the four variables was studied in 47 divers. The data were analyzed by multinomial log-linear model. The analysis showed that the 17 m/min ascent produced more elevated grades of bubbles than the 9 m/min ascent (P < 0.05), except at the 40-min interval, and showed relationships between grades of bubbles and ascent rate and age and interaction terms between VO(2 max) and age, as well as VO(2 max) and percent body fat. Younger, slimmer, or aerobically fitter divers produced fewer bubbles compared with older, fatter, or poorly physically fit divers. These findings and the conclusions of previous studies performed on animals and humans led us to support that ascent rate, age, aerobic fitness, and adiposity are factors of susceptibility for bubble formation after diving.

Altered respiratory activity and respiratory regulations in adult monoamine oxidase A-deficient mice.

The abnormal metabolism of serotonin during the perinatal period alters respiratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flores et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied the respiratory activity and regulations in adult C3H and Tg8 mice. First, plethysmographic and pneumotachographic analyses of breathing patterns revealed weaker tidal volumes and shorter inspiratory durations in Tg8 than in C3H mice. Second, electrophysiological studies showed that the firing activity of inspiratory medullary neurons and phrenic motoneurons is higher in Tg8 mice and that of the intercostal motoneurons in C3H mice. Third, histological studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. dl-p-chlorophenyl-alanine treatments applied to Tg8 mice depress the high serotonin level present during adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not significantly affected. Therefore in Tg8 mice the high serotonin level occurring during the perinatal period alters respiratory network maturation and produces a permanent respiratory dysfunction, whereas the high serotonin level present in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the respiratory network and in both the respiratory activity and the respiratory regulations.

Ascent rate and circulating venous bubbles in recreational diving.

The aim of this study was to assess the effect of the ascent rate on the production of venous circulating bubbles during the decompression following a recreational dive. Twenty-eight recreational divers performed two open water dives at 35 m during 25 minutes. Ascent rate up to the decompression stop was in one case 9 meter per minute (m/min) and in the other case 17 m/min. Circulating venous bubbles were screened using continuous wave Doppler every 10 minutes during one hour after surfacing. Bubbles Doppler signals were graded according to the Spencer scale (from 0 to IV), and the Kisman integrated severity score (KISS) was calculated. Statistical analysis demonstrated a significantly higher bubbles grade and a significantly higher KISS following the rapid decompression compared to the slow one (respectively p = 0.001 and p = 0.0001). In conclusion, these results demonstrate that a 9 m/min ascent rate is safer than a 17 m/min one.

Left atrial and ventricular filling in chronic obstructive pulmonary disease. An echocardiographic and Doppler study.

Abnormal left ventricular (LV) diastolic function has frequently been reported in patients with chronic obstructive pulmonary disease (COPD). In the present work, diastolic function was studied by a combined analysis of pulmonary venous and mitral blood flow velocities in 34 patients with COPD clinically stable and without history of heart disease, and 20 control subjects. We confirmed the increased contribution of the atrial contraction to the LV filling in COPD patients in comparison with control subjects; furthermore, a decreased left atrial (LA) filling during the ventricular systole was observed. Changes in LV filling were not the consequence of a systolic dysfunction, because LV systolic function was normal. Doppler indices indicated that LA pressure was below 15 cm H(2)O in all the patients with COPD and control subjects. Several factors can be put forward to explain these changes; the first one is tachycardia. In addition to hypoxemia and medications, echocardiography suggested that a decreased LV preload participated in increased heart rate. Analysis of Doppler transmitral and pulmonary venous flows demonstrated the role of the ventricular interdependence because a correlation existed between LA and LV filling pattern and right ventricle pressure and diameter.

Effects of prolonged hypobaric hypoxia on human skeletal muscle function and electromyographic events.

This study tested the hypothesis that a prolonged decrease in arterial oxygen pressure in resting or contracting skeletal muscles alters their ability to develop force through an impairment of energy-dependent metabolic processes and also through an alteration of electrophysiological events. The experiment was conducted during a 32-day simulated ascent of Mt. Everest (8848 m altitude) (Everest III Comex '97), which also allowed testing of the effects of re-oxygenation on muscle function. Maximal voluntary contractions (MVCs) of the flexor digitorum, and static handgrips sustained at 60% of MVC, were performed by eight subjects before the ascent (control), then during the stays at simulated altitudes of 5000 m, 6000 m and 7000 m, and finally 1 day after the return to 0 m. The evoked muscle compound action potential (M-wave) was recorded at rest and during the manoeuvres at 60% of MVC. The changes in median frequency of electromyographic (EMG) power spectra were also studied during the contraction at 60% of MVC. In four individuals, transient re-oxygenation during the ascent allowed us to test the reversibility of hypoxia-induced MVC and M-wave changes. At rest, a significant decrease in M-wave amplitude was noted at 5000 m. This effect was associated with a prolonged M-wave conduction time at 6000 m and an increased M-wave duration at 7000 m, and persisted after the return to 0 m. Re-oxygenation did not modify the changes in M-wave characteristics. A significant decrease in MVC was measured only during the ascent (-10 to -24%) in the non-dominant forearm of subjects who underwent re-oxygenation; this intervention slightly improved muscle strength at 6000 m and 7000 m. During the ascent and after the return to 0 m, there was a significant reduction of the median frequency decrease throughout contraction at 60% of MVC compared with the EMG changes measured before the ascent. It is concluded that prolonged exposure to hypoxia slows the propagation of myopotentials and alters sensorimotor control during sustained effort. Re-oxygenation did not affect the hypoxia-induced EMG changes and had a modest influence on muscle strength.

Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive.

During the 7.1-MPa hydrogen-helium-oxygen record human dive, we tested the hypothesis that the increased ambient pressure would alter the maximal muscle performance, specifically that breathing dense gas would lead to fatigue of the respiratory muscle. A group of hand muscles (adductor pollicis, AP) and the inspiratory muscles (IM) were studied in three professional divers. Maximal voluntary contractions (MVC) of AP and maximal inspiratory pressure (P(i(max))) generated by IM were measured prior to the dive, during compression and decompression, and then 1 and 2 months after the dive. The decrease in MVC (-22%) was significant at 3.1 MPa, i.e. at the beginning of the introduction of hydrogen into the breathing mixture, whereas P(i(max)) fell progressively during the dive and decompression (maximal DeltaP(i(max)) = -55%), a significant reduction still being measured 1 month after the dive. The altered IM function was attributed to the consequences of long-term ventilatory loading, a condition associated with breathing a dense gas. The transient decrease in MVC of the skeletal muscle would indicate a possible effect of the hyperbaric environment, possibly the high partial pressure of hydrogen, on neuromuscular drive.

Operation Everest III (Comex '97): modifications of cardiac function secondary to altitude-induced hypoxia. An echocardiographic and Doppler study.

During Operation Everest III (Comex '97), to assess the consequences of altitude-induced hypoxia, eight volunteers were decompressed in a hypobaric chamber, with a decompression profile simulating the climb of Mount Everest. Cardiac function was assessed using a combination of M-mode and two-dimensional echocardiography, with continuous and pulsed Doppler at 5,000, 7,000, and 8,000 m as well as 2 d after return to sea level (RSL). On simulated ascent to altitude, aortic and left atrial diameters, left ventricular (LV) diameters, and right ventricular (RV) end-systolic diameter fell regularly. Heart rate (HR) increased at all altitudes accompanied by a decrease in stroke volume; in total, cardiac output (Q) remained unchanged. LV filling was assessed on transmitral and pulmonary venous flow profiles. Mitral peak E velocity decreased, peak A velocity increased, and E/A ratio decreased. Pulmonary venous flow velocities showed a decreased peak D velocity, a decreased peak S velocity, and a reduction of the D/S ratio. Systolic pulmonary arterial pressure (Ppa) showed a progressive and constant increase, as seen on the elevation of the right ventricular/right atrial (RV/RA) gradient pressure from 19.0 +/- 2.4 mm Hg at sea level up to 40.1 +/- 3.3 mm Hg at 8,000 m (p < 0.05), and remained elevated 2 d after recompression to sea level (SL) (not significant). In conclusion, this study confirmed the elevation of pulmonary pressures and the preservation of LV contractility secondary to altitude-induced hypoxia. It demonstrated a modification of the LV filling pattern, with a decreased early filling and a greater contribution of the atrial contraction, without elevation of LV end-diastolic pressure.

Dietary fish oil promotes positive inotropy of ouabain in the rat heart.

We tested the hypothesis that a fish oil (FO) diet promotes positive inotropy of ouabain without increased toxicity. For 2 mo, two groups of adult male rats were fed 1) a regular food diet supplemented with dietary long-chain polyunsaturated fatty acid from FO or 2) a regular food diet (control). The responsiveness to ouabain was evaluated for the two groups in Langendorff-perfused hearts, by (31)P nuclear magnetic resonance spectroscopy, and on purified membrane-bound Na-K-ATPase. The maximum positive inotropy achieved with ouabain was nearly two times higher in the FO than in the control group and was not associated with significant changes in energetics. Alteration of function and energetic metabolism and inhibition of Na-K-ATPase in response to 3 x 10(-4) M ouabain were delayed in the FO group. This study demonstrates that dietary FO, by a cardiac membrane incorporation of n-3 polyunsaturated fatty acid, promotes positive inotropy of ouabain without toxicity and changes in cardiac metabolism.

Circulating venous bubbles in recreational diving: relationships with age, weight, maximal oxygen uptake and body fat percentage.

Decompression sickness (DCS) is recognized as a multifactorial phenomenon depending on several individual factors, such as age, adiposity, and level of fitness. The detection of circulating venous bubbles is considered as a useful index for the safety of a decompression, because of the relationship between bubbles and DCS probability. The aim of this work was to study the effects of individual variables which can be assessed non invasively, on the grades of bubbles detected 60 min, after diving by means of Doppler monitoring, in a sample of 40 male recreational scuba divers. The variables investigated were: age, weight, maximal oxygen uptake (VO2max) and percentage of body fat (%BF). Bubble signals were graded according to the code of Spencer. The relationships between the bubble grades (BG) and the variables investigated were studied using two methods: the differences between the average values of each variable at each BG were analyzed by the Scheffe test. Then we performed the non-parametric Spearman correlation analysis. Significant differences (P < 0.05) were found (Scheffe test) between average values of the variables at grade 0 and 3 (age: P = 0.0323; weight: P = 0.0420; VO2max: P = 0.0484), except for %BF (P = 0.1697). Relationships with P < 0.01 were found (Spearman correlation) between BG and the variables: age: p = 0.486, P = 0.0024; weight: p = 0.463, P = 0.0039; VO2max: p = -0.481, P = 0.0027; except for %BF: p = 0.362, P = 0.0237. This work showed that bubble production after hyperbaric exposures depends on several individual factors. The effects of age, weight and VO2max are more significant than the effect of %BF. We concluded that to take into account such variables in decompression tables and diving computer programs should allow to adapt the decompression procedures to individual risk factors and reduce the DCS probability.

Pulmonary stretch receptor discharges and vagal regulation of respiration differ between two mouse strains.

1. Experiments were performed on adult pentobarbitone-anaesthetized mice of the OF1 and the C3H/HeJ (C3H) strains, to analyse the regulation of respiration by pulmonary stretch receptors (PSRs). 2. Although the mean respiratory period, inspiratory and expiratory durations, and tidal volume did not differ significantly between the two strains, the inspiratory onset was drastically inhibited in OF1 mice but only slightly inhibited in C3H mice in response to tracheal occlusion performed at the very end of inspiration. 3. Low current electrical stimulation of the vagus nerve induced inspiratory onset inhibition in both strains, suggesting that the weak inspiratory onset inhibition elicited by tracheal occlusion in C3H mice did not originate from a low sensitivity of the respiratory centres to PSRs. 4. During normal respiration, PSR firing rate increased with tidal volume, but reached significantly higher values in OF1 than C3H mice. During tracheal occlusion, PSR firing rate was significantly higher at the end of inspiration and during the first third of the occlusion period in OF1 than C3H mice. 5. The airway pressure resistance was significantly higher in OF1 than C3H mice. After abolishing the tracheo-bronchial muscle tone with atropine in OF1 mice, tracheal occlusions induced weak inspiratory onset inhibitions resembling the C3H mouse responses. 6. The possibility that differences in tracheo-bronchial tone between OF1 and C3H mice may lead to a greater PSR discharge and thus to a powerful inhibition on the OF1 medullary respiratory centres during tracheal occlusion is discussed.

Changes in airway resistance induced by nasal or oral intermittent positive pressure ventilation in normal individuals.

Nasal intermittent positive-pressure ventilation (nIPPV) is used for the treatment of respiratory failure in patients with neuromuscular disease. The aim of the present study was to demonstrate that nIPPV may activate nose receptors, the consequence of which being reflex changes in lung resistance. The changes in interrupter resistances (Rint) in response to nIPPV were tested before and after local anaesthesia of the nasal mucosa in normal subjects. They were compared to the Rint changes induced by oral intermittent positive-pressure ventilation (oIPPV) in the same individuals. Rint was measured during 10-min periods of nIPPV or oIPPV at a constant rate (15 L x min(-1)), but at two different stroke volumes (0.8 and 1.2 L). Inspired temperature and relative humidity were held constant. nIPPV with 1.2 L (17 mL x kg(-1)) significantly increased the Rint value (+22%). This effect disappeared after nose anaesthesia or after inhalation of a cholinergic antagonist. oIPPV never changed Rint, even though the associated hypocapnia was present and more accentuated than during nIPPV. Adding CO2 to the inspired gas during nIPPV and oIPPV trials suppressed the Rint changes. The present study suggests the existence of a nasopulmonary bronchoconstrictor reflex elicited through the stimulation of nasal mechanoreceptors, their activity being markedly influenced by the changes in expired CO2 concentration.

Long-term exposure of adults to outdoor air pollution is associated with increased airway obstruction and higher prevalence of bronchial hyperresponsiveness.

The authors studied the association between long-term exposure (i.e., > 10 y) to outdoor air pollution and the severity of obstructive pulmonary disease and prevalence of bronchial hyperreactivity to beta2 agonists in two groups of adult patients who were of similar ages and who had similar smoking habits. The subjects lived in downtown districts or in the outer suburbs of Marseilles, the neighborhood that contained air samplers. The regions were similar with respect to sulfur dioxide levels, but levels of nitric oxides and particulate matter (10 millimeters or less) were higher in the downtown area than the suburbs. The authors assessed airway obstruction, as determined by a decrease in forced expiratory volume in 1 s, mean forced expiratory flow measured between 25% and 75% of vital capacity, and an elevated value of central airway resistance. The authors tested the changes in these variables induced by inhalation of a beta2 agonist. Baseline lung function was altered more significantly in both male and female patients who lived in downtown Marseilles than in those who resided in the suburbs, and the differences persisted regardless of the season during which the study occurred. Prevalence of bronchial hyperreactivity and symptoms of asthma (but not of rhinitis) were higher in the downtown than suburban male subjects. The results of this study suggest that an association exists between actual environmental exposure to outdoor air pollution (i.e., nitrogen oxides and/or particulate matter of 10 millimeters or less) and respiratory effects in sensitive adults represented by patients with chronic obstructive pulmonary disease or asthma.

Influence of respiratory afferents upon the proprioceptive reflex of skeletal muscles in healthy humans.

Relationships between respiratory afferents and the motor drive to skeletal muscles are well documented in animals, but human data are scarce. Tonic vibratory response (TVR) elicited by mechanical tendon vibrations were explored in an arm (extensor digitorum, ED) and a leg (vastus lateralis, VL) muscle, in healthy subjects. Tendon vibrations were delivered during unloaded breathing and after 10 breathing cycles while the subject breathed through an inspiratory or expiratory resistive load in order to activate respiratory afferents. Inspiratory loaded breathing significantly enhanced TVR in ED and VL muscles whereas the effects of expiratory loading depended on the vibrated muscle (increased TVR in ED; decreased TVR in VL). These results suggest that inspiratory muscle afferents activated during inspiratory loading facilitate the gamma motor drive to arm and leg muscles whereas the activation of pulmonary vagal afferents during expiratory loading can exert a facilitating or suppressive influence on the gamma motor drive, depending on the limb muscle group.

Nasal eupnoeic inhalation of cold, dry air increases airway resistance in asthmatic patients.

The aim of this study was to establish a relationship between bronchial hyperreactivity to carbachol and reflex bronchomotor response to the activation of cold receptors in the nose, and also to examine whether any differences exist between asthmatic patients with or without symptoms of rhinitis. The changes in interrupting resistance (Rint) induced by nasal eupnoeic inhalation of cold (-5 degrees C) dry air were measured in 22 normal subjects and in 18 asthmatic patients (nine of whom had asthma with rhinitis and nine without) with bronchial hyperreactivity to carbachol. In normal individuals, nasal cold air challenge induced a significant increase in Rint (+31%). This was also the case in asthmatic patients (asthma with rhinitis +49%; asthma alone +40%), but the increase was not significantly larger than for normal individuals. The magnitude of Rint increase induced by nasal cold air breathing was correlated with the sensitivity to carbachol (defined as the dose inducing a 50% increase in specific airway conductance (D50)) in asthmatic patients with symptoms of rhinitis. These observations suggest that airway hyperreactivity is associated with enhanced bronchoconstrictor response to the activation of nasal cold receptors, particularly when rhinitis is present.

Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in normal individuals.

Nasopulmonary bronchomotor reflexes elicited by mechanical or irritant stimulation of the nose have been described in animals and asthmatic patients. However, few studies were devoted to the consequences of nasal breathing of cold and dry air or of only dry or only moist air on the bronchomotor control in normal individuals. The present study reported changes in interruption resistance (Rint) measured during eupneic breathing of moderately cold (-4 or -10 degrees C) and dry [0.3% relative humidity (RH)] air or of room air at 23 degrees C that is either dry (0.3% RH) or moist (97% RH). Nasal inhalation of cold (-4 degrees C) dry air or of only dry air significantly increased baseline Rint value (17 and 21%, respectively) throughout the 15-min test periods. The response to cold was significantly accentuated when the air temperature was lowered to -10 degrees C (42%). After nasal anesthesia or inhalation of a cholinergic antagonist, cold air did not induce a change in Rint. Nasal inhalation of moist room air had no effect. No Rint changes were measured during oral breathing of the three test agents. It is concluded that the activation of cold receptors or osmoreceptors in the nasal mucosa induces protective bronchoconstrictor responses in normal individuals.

The sensation of respiration in men experiencing high-altitude chronic hypoxia.

Respiratory sensation was studied in seven European lowlanders during a Himalayan expedition at over 6000 m. At rest, the ability to detect added inspiratory resistive loads can be used to create a sensitivity index P(A) taking response bias (B) into account based on Sensory Decision Theory. The data indicate that respiratory sensitivity may be involved in successful adaptation to hypoxia. Respiratory sensitivity improved during the first stages of exposure to altitude and returned to baseline after 17- and 27-day stays under chronic hypoxic conditions. The improvement in respiratory sensation could be a primary signal in the physiological and psychological adaptation to high altitude and change in sensation may reflect the degree of altitude adaptation.

Central inhibitory effect of adenosine deaminase on carotid blood flow increase at high pressure.

Carotid blood flow in rats was measured by implanted transit-time ultrasonic flowprobes throughout hyperbaric experiments conducted up to 70 bar (7 MPa) with a helium-oxygen hyperoxic (PO2 = 400 mbar) mixture. Before the hyperbaric experiment, an intracerebroventricular (ICV) injection of phosphate saline-buffered solution (PBS) or adenosine deaminase (ADA, 100 U.ml-1) in PBS was performed. Throughout the hyperbaric experiment carotid blood flow increased with ambiant pressure in PBS-treated rats. Conversely, the increase in carotid blood flow was attenuated by ADA treatment. These results suggest that the increase in carotid blood flow at high ambiant pressure could result from an increase of adenosine concentration in the rat brain.