Reduction of olfactory sensitivity during normobaric hypoxia.

OBJECTIVE: Acute mountain sickness (AMS) is caused by a low partial pressure of oxygen and may occur above 2500m. The aim of this research was to evaluate olfactory and gustatory abilities of healthy subjects during baseline conditions and after seven hours of normobaric hypoxia. METHODS: Sixteen healthy subjects were assessed using the Sniffin' Sticks, as well as intensity and pleasantness ratings. Gustatory function was evaluated utilizing the Taste Strips. Experiments were carried out under baseline conditions (518m altitude) followed by a second testing session after seven hours of normobaric hypoxia exposure (comparable to 4000m altitude). RESULTS: During normobaric hypoxia olfactory sensitivity and intensity estimates were significantly reduced. CONCLUSIONS: We conclude that normobaric hypoxia leads to a significant decrease of olfactory sensitivity and intensity ratings.

Susceptibility-weighted angiography visualizes hypoxia in cerebral veins.

OBJECTIVES: The objective of this study was to evaluate the influence of short- and long-term hypoxia on the depiction of cerebral veins in the susceptibility-weighted angiography (SWAN) sequence. MATERIALS AND METHODS: In the context of a study on brain adaptation mechanisms to hypoxia, 16 healthy men (aged 20-28 years) were studied through magnetic resonance imaging (MRI) under room air conditions, short-term-hypoxia (7 minutes before and during the MRI scan), and long-term hypoxia (8.5 hours before and during the MRI scan). Oxygen saturation was continuously measured using a finger-mounted pulse oximeter. Two independent blinded readers compared the 3 scans of each participant and graded the SWAN source images and minimum intensity projections according to the size, number, and signal intensity of the cerebral veins. Signal intensities of deep cerebral veins were measured, and signal intensity proportions of deep cerebral veins to different parenchymal brain regions were calculated. RESULTS: Nine subjects could be included in the study. In all of them, both readers correctly distinguished the 2 hypoxia scans from the baseline scan, grading the SWAN images acquired under hypoxic conditions as visualizing cerebral veins more prominently. Signal intensities of the deep cerebral veins and signal intensity proportions were significantly lower in the hypoxia scans. No significant differences between short-term and long-term hypoxia were found on visual inspections and signal intensity measurements. This correlated with the results of the pulse oximetry: mean O2 saturation values were 97.9% ± 1.2% (baseline), 84.1% ± 3.8% (short-term hypoxia), and 82.8% ± 4.4% (long-term hypoxia), respectively. CONCLUSIONS: Hypoxia leads to visible and measurable changes in cerebral veins as depicted through SWAN. Possible clinical implications of this finding include stroke and tumor imaging and need further investigation.

No evidence of intracranial hypertension in trekkers with acute mountain sickness when assessed noninvasively with distortion product otoacoustic emissions.

AIMS: The role of intracranial hypertension in acute mountain sickness (AMS) is a matter of debate. Distortion product otoacoustic emissions (DPOAEs) can be used to monitor the intracranial pressure (ICP) noninvasively with a level decrease at the frequencies f2=1 and 1.5 kHz indicating elevated ICP. METHODS: DPOAEs (f2=1, 1.5, 2, 3, and 4 kHz), oxygen saturation (Sao2) and the Lake Louise score (LLS) to assess AMS were measured in trekking tourists on the Mount Everest trek in Nepal at 2610 m and 5170 m. RESULTS: Paired data of both altitudes could be obtained of 187 subjects. All results are given in mean±SD. Sao2 was 94.8±2.7% at 2610 m and 79.0±6.9% at 5170 m. While at 2610 m, none of the study subjects had AMS (LLS 0.04±0.02), at 5170 m 82 (43.9%) had AMS when defined as LLS>2, and 31 (16.6%) when defined as LLS>4 (LLS 2.8±2.2). DPOAE levels decreased at altitude in all frequencies without a difference between trekkers with AMS and without AMS. Low Sao2 correlated with high LLS. Low Sao2 correlated with larger DPOAE level decrease only at f2=1 kHz, while the other frequencies showed no correlation. DPOAE level decrease and LLS showed no correlation. CONCLUSIONS: Our data suggest that subjects with AMS symptoms did not have higher ICP compared to healthy subjects. Consequently, it seems unlikely that intracranial hypertension accounts for the symptoms of AMS.

Complex level alterations of the 2f(1)-f(2) distortion product due to hypoxia.

OBJECTIVE: For diagnostic purposes and a better understanding of the pathophysiology of inner ear hearing disorders it would be of great interest to have parameters available that indicate inner ear hypoxia. In animal studies typical hypoxia-related alterations of the 2f1-f2 distortion product otoacoustic emissions (DPOAE) such as a reversible level decrease and destabilization could be demonstrated. The goal of this study was to investigate whether these hypoxia-associated alterations can also be observed in humans because this might help develop a new diagnostic tool for patients with inner ear disorders. METHODS: In 16 volunteers DPOAE levels were continuously measured at first under normal room air conditions, during and after 8.5h of oxygen deprivation (13% O2) and during re-oxygenation. Saturation of oxygen of arterial blood (SaO2) was monitored. RESULTS: The mean SaO2 during the hypoxic interval was 78%. A significant decrease in DPOAE level under hypoxia occurred in five different test persons at one or more frequencies (f2=1, 1.5, 2, 3, and 4kHz). A destabilization of the DPOAE level with considerable fluctuations during hypoxia was observed in nine subjects at one or more frequencies. Furthermore, the so called 'post hypoxia effect' could be observed in five participants. CONCLUSION: The observations made here have been described similarly in animal studies and seem to be characteristic of metabolic disorders of the cochlea caused by hypoxia. To our knowledge, this is the first study to examine DPOAE level alterations over time in humans under conditions of normobaric hypoxia. If DPOAE destabilization is observed in a clinical setting in patients with certain inner ear hearing disorders hypoxia can be suspected as one underlying pathophysiological cause which might influence treatment decisions.

Level alterations of the 2f (1)-f (2) distortion product due to hypoxia in the guinea pig depend on the stimulus frequency.

Increased intracranial pressure (ICP) is known to affect the levels of distortion product otoacoustic emissions (DPOAEs) in a frequency-specific manner. DPOAEs might, therefore, be used for monitoring the ICP non-invasively. Hypoxia can also cause alterations of DPOAE levels, which can be distinguished from ICP-related changes only, when their characteristics, in particular frequency specificity, are known in detail. DPOAEs at f (2) = 2, 4, 8, 12 and 16 kHz and oxygen saturation (SaO(2)) were continuously monitored in nine spontaneously breathing guinea pigs, anaesthetized by i.m. administration of midazolam, medetomidin and fentanyl, during the respiration of a gas mixture of N(2)O and O(2) containing either 30% O(2) or 13% O(2). Fourteen hypoxic intervals in eight animals were included into final data analysis. Characteristic hypoxic level alterations with a level decrease and a remarkable level destabilization during hypoxia, and a pronounced reversible level decrease after reoxygenation were observed at the frequencies of 4, 8 and 16 kHz. At 2 and 12 kHz, the only reproducible effect of hypoxia was an increased fluctuation of the DPOAE level, which was significantly less pronounced compared with the other frequencies (P < 0.05 for 12 vs. 16 and 8 kHz and for 2 vs. 16 kHz). DPOAE level alterations due to hypoxia depend on the frequency in guinea pigs. Studies in human are warranted to improve non-invasive ICP monitoring with DPOAE by the detection of hypoxia-related changes.

Polygraphy of sleep at altitudes between 5300 m and 7500 m during an expedition to Mt. Everest (MedEx 2006).

OBJECTIVES: Sleep at extreme altitudes is characterized by the repetitive occurrence of central apneas that in some cases may lead to a marked decrease in arterial oxygen saturation. During the Ludwig Maximilians University Expedition to Mt. Everest (MedEx 2006), nocturnal polygraphic recordings were made at different altitudes and included the first recordings ever made at 7500 m, which were completed on 8 separate occasions during the expedition. METHODS: The study was performed on the author (K.M., 58 years, 181 cm, 75 kg), who is an experienced high-altitude mountaineer. The standard polygraphic parameters, such as nasal and oral airflow, thoracic and abdominal effort, oxygen saturation, heart rate, body position, movement, and snoring, were collected with a portable sleep recording device (AlphaScreen, SensorMedics, Germany, Hochberg) at different altitudes between 5300 m and 7500 m, and were compared with baseline assessments made in Munich, Germany (altitude 508 m). The daytime value of oxygen saturation at rest was measured at South Col (8000 m) and at the South Summit (8763 m) without breathing supplemental oxygen for at least 10 minutes. RESULTS: The number of apneas and hypopneas of central origin increased up to a maximum of 148/h with a minimal blood oxygen saturation of 48% at 7500 m, compared with <5/h at Munich. After 11 days of acclimatization, data recorded at 5300 m showed a marked reduction of disturbed sleep. The Apnea-Hypopnea-Index dropped from 138/h to 51/h, and the minimal blood oxygen saturation rose from 57% to 67%. At South Col (8000 m), the daytime value of oxygen saturation at rest ranged between 53% and 55%, and on South Summit (8673 m) without breathing supplemental oxygen for at least 10 minutes, it fluctuated around 50%. CONCLUSIONS: These data correlate well compared with those obtained in hypobaric chamber studies and show that regardless of physiologic adjustment to low oxygen conditions at Base Camp altitude, during the final summit attempt oxygen saturation drops further to 55% and even less. Thus recordings of nocturnal oxygen saturation at Camp 3 (7500 m) on Everest, where the night is spent before the summit attempt, may help to show the actual efficiency of hypoxic ventilatory response and to detect the individual hypoxic tolerance to altitudes above 8000 m.

Complex level alterations of the 2f (1)-f (2) distortion product due to hypoxia in the guinea pig.

It is controversially discussed inasmuch acute hearing disorders might originate from impaired cochlear circulation. Hypoxia-specific alterations of inner ear parameters measurable in patients with acute sensorineural hearing loss would therefore be of great interest. Aim of this study was to characterize hypoxia-related alterations of the 2f (1)-f (2) distortion product. Nine guinea pigs were anaesthetized by i.m. administration of Midazolam, Medetomidin and Fentanyl. For introduction of hypoxia, the spontaneously breathing animals were offered a gas mixture of N(2)O and O(2) containing either 21 or 12-13% O(2). Distortion product otoacoustic emissions (DPOAEs) were continuously monitored at f (2) = 16 kHz; f (2)/f (1) = 1, 2; DP-definition = 2f (1)-f (2); L (1) = 65 dB and L (2) = 55 dB, while inhaled oxygen was switched from 21 to 12-13% and back. Oxygen saturation (SaO(2)) was continuously monitored. Data from an hypoxic interval were only used for further data processing if DPOAE levels were stable before and after hypoxia. Six hypoxic intervals in five animals fulfilled the stability criterion. During the hypoxic interval with the highest measured SaO(2) (75%), no alterations of DPOAE levels were observed. During the remaining five hypoxic intervals, when SaO(2) ranged between 57 and 70%, DPOAE levels were on average lower with an increased standard deviation compared to mean pre-hypoxic levels. Mean decrease correlated with the decrease of SaO(2 )(r = 0.90, P = 0.014). Alterations followed a characteristic time course-when hypoxia was started, DPOAE levels exhibited a short increase before they decreased and remarkably destabilized. After re-oxygenation DPOAE levels showed a pronounced level decrease, while SaO(2) already had recovered to pre-hypoxic values. After reaching a minimum, DPOAE levels slowly recovered to pre-hypoxic values. The decrease of DPOAE levels during hypoxia and the post-hypoxic level alterations have similarly been described by other authors before, while the distinct destabilization and transiently increased DPOAE levels have not been explicitly mentioned. A micromechanical mechanism that might explain a transient level increase and the post-hypoxic DPOAE level changes is discussed.

Distortion product otoacoustic emissions for assessment of intracranial hypertension at extreme altitude?

The levels of distortion product otoacoustic emissions (DPOAEs) change at frequencies between 0.75 and 1.5 kHz along with intracranial pressure (ICP) and DPOAEs are suggested for monitoring ICP changes. Elevated ICP plays a major role in high-altitude disease, but direct measurement is unlikely to be feasible at high altitudes. The aim of the presented study was to measure DPOAEs at extreme altitudes in order to determine whether information about elevated ICP can be obtained. Data are presented from DPOAE measurements at the frequencies 1, 1.5, 2, 3 and 4 kHz in 13 climbers during an ascent to Gasherbrum II (8,035 m) up to an altitude of 7,400 m. Valid DPOAE measurements could be obtained in all climbers. DPOAE levels exhibited great variability concerning both the affected frequency range and the change. As expected due to elevated ICP, DPOAE levels decreased in some of the climbers at 1 kHz. However, an even more pronounced decline of DPOAE levels was observed at 3 and 4 kHz, which cannot be explained by intracranial hypertension. Possible other reasons for DPOAE level changes at extreme altitude are hypoxia, increased serum osmolarity and unbalanced middle ear pressure. Only one climber developed severe acute mountain sickness with clinical signs of intracranial hypertension. The most pronounced decline of DPOAEs at 1 kHz was seen on that occasion, which suggests a possible use of DPOAEs for detection of intracranial hypertension and early detection of high-altitude cerebral edema.

Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity.

HYPOTHESIS: In this study we tested the effect of local administration of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window membrane. BACKGROUND: Cisplatin is an important antineoplastic agent in the therapy of many malignancies. Its clinical utility is limited by severe side effects, including ototoxicity. Recent studies have shown protection against cisplatin ototoxicity in animal experiments by the systemic administration of D-methionine and sodium thiosulfate. Growth factors such as brain-derived neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective effects in in vitro studies. METHODS: Osmotic pumps (Alzet) were implanted unilaterally in 30 guinea pigs. Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally for 5 consecutive days. Distortion product otoacoustic emissions were recorded every day. The animals were killed on day 6, and their cochleae were removed and analyzed by transmission electron microscopy. RESULTS: Compared with control animals, guinea pigs treated with D-methionine showed better otoacoustic emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 showed no significant protective effect. CONCLUSION: Local application to the round window membrane can be used as an effective treatment in the prevention of cisplatin toxicity. Local application may avoid systemic side effects and reduce the antineoplastic effects of cisplatin.

Hyperfibrinogenemia as a risk factor for sudden hearing loss.

OBJECTIVE: To clarify predisposing conditions for vascular events. SETTING: Vascular events, immunologic processes, and viral infections have to be considered as pathomechanisms for most cases of sudden hearing loss. STUDY DESIGN: Hemorrheologic parameters were studied in 53 patients with sudden hearing loss within 5 days of the onset. PATIENTS: A control group of 53 normal-hearing people was matched pairwise according to age and gender. RESULTS: Fibrinogen levels were significantly higher in patients with sudden hearing loss (343 +/- 98 mg/dl) than in control subjects (303 +/- 69 mg/dl). Erythrocyte aggregation (27.3 +/- 5.6 a.u. versus 20.9 +/- 8.5 a.u.) and plasma viscosity (1.31 +/- 0.13 mPa/s versus 1.26 +/- 0.08 mPa/s) in patients with SHL were also significantly higher than in control subjects. No significant difference could be found in the parameters of clinical chemistry, hematology, and hemostasias investigated. CONCLUSION: Because elevated plasma fibrinogen plays a major role in cardiovascular diseases such as myocardial infarction and stroke, it is possible that this plasma protein is also involved in the pathogenesis of sudden hearing loss of vascular origin. More research is still required to determine the value of measuring plasma fibrinogen levels in clinical practice and identifying hyperfibrinogenemia in sudden hearing loss.