Low-dose theophylline reduces symptoms of acute mountain sickness.

OBJECTIVE: Headache, nausea, and sleeplessness at altitude [acute mountain sickness (AMS)] are major health problems for several million mountain recreationists who ascend to high altitudes each year. We aimed to test the efficacy of low-dose, slow-release theophylline for the prevention of AMS in a placebo-controlled, double-blind, randomized trial. METHODS: Twenty healthy male volunteers (mean age 34.7 y) were randomized (random allocation) to receive either 300 mg theophylline daily or placebo 5 days prior, during ascent, and during a stay at 4,559 m altitude. AMS symptoms were collected using the Lake Louise Score on each day during ascent and at high altitude. A 12-channel sleep recorder recorded sleep and breathing parameters during the first night at 4,559 m. Theophylline serum levels were drawn prior to the sleep study. RESULTS: Seventeen completed the entire study. Theophylline (n = 9) compared to placebo (n = 8) significantly reduced AMS symptoms at 4,559 m (Lake Louise Score: 1.5 +/- 0.5 vs placebo 2.3 +/- 2.37; p < 0.001), events of periodic breathing (34.3/h vs placebo 74.2/h; p < 0.05), and oxygen desaturations (62.3/h vs placebo 121.6/h; p < 0.01). No significant differences in sleep efficiency or sleep structure were present in the two groups. No adverse drug effects were reported. CONCLUSIONS: Low-dose, slow-release theophylline reduces symptoms of AMS in association with alleviation of events of periodic breathing and oxygen desaturations.

Plasma adenosine during investigation of hypoxic ventilatory response.

Adenosine, an endogenous nucleoside, is released by hypoxic tissue, causes vasodilation, and influences ventilation. Its effects are mediated by P1-purinoceptors. We examined to what extent the plasma adenosine concentration in the peripheral venous blood correlates with hypoxic ventilatory response (HVR) and ventilatory drive P0.1 to find out whether endogenously formed adenosine has an influence on the individual ventilatory drive under hypoxic conditions. While investigating the HVR of 14 healthy subjects, the ventilatory drive P0.1 was measured with the shutter of a spirometer. Determination of the ventilatory drive P0.1(RA) started under room air conditions (21% O (2)) and then inspiratory gas was changed to a hypoxic mixture of 10% O (2) in N (2) to determine P0.1(Hyp). At the time of the P0.1 measurements, two blood samples were taken to determine the adenosine concentrations. After removal of cellular components and proteins, samples were analyzed by high-pressure liquid chromatography (HPLC). Both adenosine concentrations in plasma under room air (r = 0.59, p < 0.05) and adenosine concentrations under hypoxia (r = 0.75, p < 0.01) correlated significantly with the ventilatory drive P0.1. In addition, plasma adenosine concentrations during hypoxic conditions showed a significant correlation with HVR on the 0.01 level (r = 0.71, p < 0.01). The results indicate a possible role of endogenous adenosine in the regulation of breathing in humans. We assume that endogenous adenosine influences the HVR and the ventilatory drive, probably by modulating the carotid body chemoreceptor response to hypoxia.