Kazuhiko Yoshimura

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.

Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats

The role of coagulation-fibrinolysis system in experimental autoimmune encephalomyelitis (EAE) was studied by using batroxobin, derived from the venom of the South American pit viper Bothrops atrox moojeni. Batroxobin converts circulating fibrinogen into an insoluble form and causes a profound degree of afibrinogenemia. Batroxobin treatment (30 BU/kg/day) suppressed clinical signs of cell transferred EAE; the mean cumulative clinical score for batroxobin treated rats was 3.97, while saline treated controls scored 6.9 (P < 0.01). Plasma fibrinogen concentration decreased significantly in batroxobin-treated rats. Histologically, the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated rats compared to saline-treated control rats, however, deposition of fibrin around the vessels in the spinal cord was markedly suppressed in batroxobin-treated rats. These findings suggest that batroxobin suppresses EAE by preventing fibrin deposition, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of blood brain barrier (BBB), are related prerequisites for the clinical manifestation of EAE.

Comparisons of oxygen transport between Tibetan and Han residents at moderate altitude

To compare the difference for oxygen transport between Tibetans living for generations at high altitude and acclimatized Han newcomers to high altitude, we measured the ventilatory, circulatory, metabolic, and gas exchange functions during exercise in 17 Tibetans and 19 Hans at the altitude of 3417 m. At maximal effort, the Tibetans, compared with the Hans, showed higher O 2 consumption ( V ˙ o 2 max ) (2.54±0.1 versus 2.10±0.1 liters min −1 , p p −1 , p P −1 ) was higher than that in the Hans (68.0±3.9 liters min −1 ), but the ventilatory equivalent was equal. The anaerobic threshold for absolute O 2 consumption ( V ˙ o 2 AT ) for the Tibetans and Hans was 1.91±0.1 versus 1.45±0.1 liters min −1 , respectively ( p 2 consumption (in % V ˙ o 2 max ) was 76.2±1.5 versus 70.5±2.2, respectively ( p V ˙ o 2 max correlated well with maximal cardiac output. No difference was found in the maximal heart rate between the two groups. Arterial oxygen desaturation from rest to exercise in the Hans (15.3%; 90.3–76.5%) was greater than that in the Tibetans (9.2%; 90.1–81.8%). We conclude that the lifelong exposure to an hypoxic environment has resulted in an increase in oxygen transport and improved aerobic exercise performance.

Indomethacin prevents ventilation-induced decreases in pulmonary vascular resistance of the middle region in fetal lambs.

ABSTRACT: Previously, we reported that the major site of pulmonary vascular resistance in fetal lambs occurred in the middle region defined by vascular occlusion, and that this region exhibited the greatest decrease upon ventilation with O2. To assess the relative individual contributions of ventilation and oxygenation to this decrease, we determined the distribution of pressures across the pulmonary circulation in isolated perfused lungs from 20 fetal lambs (131–137 d gestation) by inflow and outflow vascular occlusions. A membrane oxygenator was included in the extracorporeal circuit to control the Po1 at 4 kPa (30 torr) in the unventilated fetal lungs. Half of the fetal lungs were ventilated first without changing the initial gas tensions, and the others were oxygenated first by changing the initial gas tensions to a hyperoxic mixture [Po2 = 26.6 kPa (200 torr)] without ventilation. Finally, both groups of lungs were ventilated and oxygenated. In addition, indomethacin was added to the perfusate (0.112 mM, or 40 μg/mL) in half of the preparations in each group to determine the effect of prostaglandins on the distribution of pressures during these conditions. The decrease in the total pulmonary vascular resistance with ventilation and/or oxygenation was primarily due to changes in the middle pressure gradient (ΔPm). In fetal lungs without indomethacin, ventilation without oxygenation reduced ΔPm from 6.1 ± 0.8 to 2.5 ±1.0 kPa, or 74% of the total ventilation- and oxygenation-induced decrease in ΔPm (final value = 1.2 ± 0.6 kPa). In contrast, oxygenation without ventilation produced a decrease in ΔPm from 5.5 ± 0.7 to 3.8 ± 0.5 kPa, only 40% of the total decrease in ΔPm (1.2 ± 0.4 kPa). Furthermore, in fetal lungs with indomethacin, only oxygenation first caused a reduction in the resistance of the middle region, suggesting that dilator prostaglandins are not involved in the response to increased oxygen. We conclude that recruitment and/or distension of the small pulmonary vessels functionally located in the middle region by the mechanical effect of ventilation is dependent on dilator cyclooxygenase products, and that this mechanical effect is a major factor involved in the decrease in pulmonary vascular resistance occurring at birth.