Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.

We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a mechanism that does not involve augmentation of blood oxygenation. To test this hypothesis, we established safety and drug interactions for aminophylline (500 mg) plus ambrisentan (5 mg) in normoxic volunteers. Subsequently, a placebo‐controlled study was employed to test the combination in healthy resting and exercising volunteers at simulated altitude (4,267 m). No serious adverse events occurred. Drug interaction was minimal or absent. Aminophylline alleviated hypoxia‐induced headaches. Aminophylline, ambrisentan, and their…

Safety of combined bambuterol and theophylline as a potential treatment of high altitude‐induced fatigue in humans

The Effects of Sympathetic Inhibition on Metabolic and Cardiopulmonary Responses to Exercise in Hypoxic Conditions.

Objective Pre-exertion skeletal muscle glycogen content is an important physiological determinant of endurance exercise performance: low glycogen stores contribute to premature fatigue. In low-oxygen environments (hypoxia), the important contribution of carbohydrates to endurance performance is further enhanced as glucose and glycogen dependence is increased; however, the insulin sensitivity of healthy adult humans is decreased. In light of this insulin resistance, maintaining skeletal muscle glycogen in hypoxia becomes difficult, and subsequent endurance performance is impaired. Sympathetic inhibition promotes insulin sensitivity in hypoxia but may impair hypoxic exercise performance, in p…

Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.

In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9),…

The novel combination of theophylline and bambuterol as a potential treatment of hypoxemia in humans.

Hypoxemia can be life-threatening, both acutely and chronically. Because hypoxemia causes vascular dysregulation that further restricts oxygen availability to tissue, it can be pharmacologically addressed. We hypothesized that theophylline can be safely combined with the β2-adrenergic vasodilator bambuterol to improve oxygen availability in hypoxemic patients. Ergogenicity and hemodynamic effects of bambuterol and theophylline were measured in rats under hypobaric and normobaric hypoxia (12% O2). Feasibility in humans was assessed using randomized, double-blind testing of the influence of combined slow-release theophylline (300 mg) and bambuterol (20 mg) on adverse events (AEs), plasma K+,…

Magnetic anisotropy in Fe/U and Ni/U bilayers

Magnetometry measurements of Fe/U and Ni/U bilayer systems reveal a non-monotonic dependence of the magnetic anisotropy for U thicknesses in the range 0 nm - 8 nm, with the Fe/U bilayers showing a more prominent effect as compared to Ni/U. The stronger response for Fe/U is ascribed to the stronger 3d-5f hybridization of Fe and U. This non-monotonic behaviour is thought to arise from quantum well states in the uranium overlayers. Estimating an oscillation period from the non-monotonic data, and comparing it to Density Functional Theory calculations, we find that wavevector matches to the experimental data can be made to regions of high spectral density in (010) and (100) cuts of the electron…