Gou Ueda

Dexamethasone in the Treatment of Acute Mountain Sickness

Cerebral edema occurs in fatal cases of acute mountain sickness. Dexamethasone, commonly used to treat cerebral edema due to other causes, also reduces the symptoms of acute mountain sickness when given prophylactically. However, the efficacy of dexamethasone in the treatment of established acute mountain sickness remains uncertain. To investigate this question, we exposed six men in a hypobaric chamber to a simulated altitude of 3700 m (barometric pressure, 64 kPa [481 mm Hg]) for 48 hours on two occasions. Acute mountain sickness was diagnosed with use of a symptoms questionnaire, and dexamethasone (4 mg every six hours) or placebo was then given in a randomized, double-blind, crossover fashion. Dexamethasone reduced the symptoms of acute mountain sickness by 63 percent (P less than 0.05), whereas placebo had a minimal effect (reduction by 23 percent; P not significant). In spite of this response, one subject had mild cerebral edema on brain CT after both placebo and dexamethasone. Dexamethasone had no effect on fluid shifts, oxygenation, sleep apnea, urinary catecholamine levels, the appearance of chest radiographs or perfusion scans, serum electrolyte levels, hematologic profiles, or the results of psychometric tests. Dexamethasone treatment was complicated by mild hyperglycemia in all subjects (mean [+/- SE] glucose level, 7.3 +/- 1.3 mmol per liter [132 +/- 23 mg per deciliter]). We conclude that dexamethasone effectively reduces the symptoms of acute mountain sickness. However, it did not improve objective physiologic abnormalities related to exposure to high altitudes. We therefore recommend that dexamethasone be used only when descent is impossible, or to facilitate cooperation in evacuation efforts.

Influence of hypoxia and pulmonary air embolism on lung injury in perfused rat lungs.

We investigated the influence of low oxygen ventilation, air-bubble infusion into the pulmonary artery and their synergistic effect on pulmonary hemodynamics and microvascular permeability in isolated perfused rat lungs. Pulmonary arterial pressure was significantly increased by 70 min of ventilation with 3% O2 (hypoxia, group H); by 0.2-ml air-bubble infusion (pulmonary air embolism, group AE), and by 0.2-ml air-bubble infusion and 70 min of 3% O2 ventilation (hypoxia and pulmonary air embolism, group H & AE) compared with that of a control group (0.2 ml saline infusion, group C). Neither total (TPR) nor arterial (Ra) pulmonary vascular resistance in group H showed any difference compared to control values. TPR and Ra in groups AE and H & AE were significantly higher than those in group C. However, there was no significant difference in TPR or Ra between groups AE and H & AE. The pulmonary capillary fluid filtration coefficient, dry lung to wet lung weight ratio and white blood cell count in the perfusate of group H were not changed, while those of the groups AE and H & AE were significantly increased compared to those of controls. However, there was no significant difference in these values between groups AE and H & AE. Since hypoxia did not damage isolated perfused rat lungs, as determined by hemodynamics and permeability, nor enhance lung injury caused by air embolism, it was suggested that air embolism contributed more to high-altitude lung injury than low oxygen.

Effects of high altitudes on finger cooling test in Japanese and Tibetans at Qinghai Plateau

The influences of both hypobaric hypoxia and cold on peripheral circulation were studied using the finger cooling test (measurement of the decrease in finger temperature, measured at the dorsal surface of the finger, during immersion of the hand in 0° C water for 20 min) at Qinghai Plateau. The same test was carried out at simulated altitudes in a 25° C climatic chamber to separate the hypobaric hypoxia influence from that of cold. In Japanese subjects at Qinghai Plateau there was a significant difference between finger skin temperatures (FSTs) during 20 min of 0° C water immersion at altitudes of 2260 m and 4860 m by ANOVA. Mean finger skin temperature during the 20-min immersion (5–20 min, MST) measured at 4860 m was significantly lower than that at 2260 m. In Tibetan subjects, there was also a significant difference between FSTs at 2260 m and at 4860 m by ANOVA. MST at 4860 m tended to be lower than that at 2260 m. In the 25° C climatic chamber, there was a significant difference between FSTs of Japanese expedition members at 2000 m and at 4000 m by ANOVA. MST was higher at 4000 m than at 2000 m, contrary to the data obtained in Qinghai. In conclusion, the higher skin temperature in response to local cold immersion, which would have been caused by stronger hypobaric hypoxia, must have been masked by the lower ambient temperature.

Nocturnal periodic breathing and arterial oxygen desaturation in acute mountain sickness

The objective of this case-control study was to investigate the relationship between periodic breathing (PB) and acute mountain sickness (AMS). Nine volunteers, healthy lowlanders between the age of 20 and 36 years stayed at a simulated altitude of 3700 m (485 Torr) for 24 h in a hypobaric chamber. A sleep study was carried out for more than 6 h. Arterial oxygen saturation (SaO 2 ) was monitored by finger oximetry on all subjects. PB was determined by a polysomnography (EEG, EOG, thoracic movement) in six subjects and was indirectly measured by studying the cyclic change of SaO 2 in three other subjects. The severity of AMS was assessed with the Environmental Symptoms Questionnaire. All subjects showed lower SaO 2 during sleep than when awake (65.0±6.4% versus 72.6±6.4%, p

Effect of cyclic guanosine monophosphate on hypoxic and angiotensin-II-induced pulmonary vasoconstriction

We examined, in isolated blood perfused rat lungs, the effect of the cell permeable 8-bromo derivative of cGMP on pulmonary vasoconstriction induced by either alveolar hypoxia or angiotensin II. 8-Bromo cGMP dose-dependently reduced both hypoxia-(IC50=2.2 × 10−5 M) and angiotensin-II-induced pulmonary vasoconstriction (IC50=5.0 × 10−5 M). This effect of 8-bromo cGMP on pulmonary vasoconstriction was not affected by cyclooxygenase blockade. M & B 22948 (0.1 mM), an inhibitor of cGMP-phosphodiesterase, reduced synergistically with 8-bromo cGMP the hypoxiaor angiotensin-II-induced vasoconstriction. The cGMP-phosphodiesterase inhibitor M & B 22948, by itself, selectively reduced hypoxia-induced vasoconstriction, suggesting a modulating effect of endogenous cGMP during hypoxic vasoconstriction.

Comparison of muscle force, muscle endurance, and electromyogram activity during an expedition at high altitude.

Handgrip force (HF), maximal pinch force (MF), muscle endurance (ME), and the median power frequency (MdPF) of the activity shown in the electromyogram (EMG) were studied at various altitudes in eight normal healthy subjects. MF and ME were measured between the index finger and thumb, and all measurements were obtained at altitudes ranging from 610 to 4860 m during an expedition in the Qinghai Plateau in China. With the change in altitude HF, ME, and MF showed no significant change. Compared to the MdPF at 2260 m on ascent, the MdPF at other altitudes showed a significant decrease (P<0.01). Thus, we conclude that muscle performance (HF, MF, and ME) was not affected by the environment at high altitude. However, MdPF was affected and the mean MdPF at 610 m after the expedition did not recover to initial values of MdPF. We suggest these results may have been affected by fatigue and chronic exposure to the hypobaric hypoxic environment, since the members of the expedition party expressed feelings of sluggishness and fatigue after the expedition.

Wave pattern analyses for cold vaso-oscillation

By immersion of rabbits earlobes into a cold liquid at −5 to −10‡C, the blood vessels begin to constrict or dilate alternately. This is reflected in the vessel temperature: temperatures were recorded and the patterns analyzed. In each unit wave, the height and the period were designated as X and Y. From a series of about 10 waves, the standard deviation SD, coefficient of variation CV and correlation coefficient R for X and/or Y were obtained. These were considered as three fundamental parameters describing the characteristics of scatter diagrams for X and Y. The successive changes of RXY for the diagrams indicated in most cases the periodic tendency. In such cases, it can be regarded as a pantograph-like change of the successive scattered diagrams. The time course of CV also showed a similar tendency but nonperiodic time courses sometimes appeared. For weaker stimuli above 0‡C, the wave patterns tended to become more irregular.

Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m

Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400m to 2800m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individuals maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n=15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n=51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n=18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.

Morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia.

We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4‐week‐old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high. These data showed that in well developed rats under chronic hypoxia, there is good development of capillary supply with corresponding restriction of cardiac hypertrophy, while hematocrit count and mitochondria are also affected.