Blood pressure stabilization as a therapeutic approach to reverse high altitude induced loss of physical capacity

Disruption of blood pressure homeostasis is a known complication of acute exposure to high altitude. We found that rats that are acutely exposed to hypobaric hypoxia and treated with a combination of the cardiac stimulant theophylline and the pulmonary vasodilator sitaxsentan run longer until exhaustion on a rodent exercise system. In addition to studying hemodynamic effects of this treatment, we have explored if other cardiac stimulants and pulmonary vasodilators have similar beneficial effects compared to theophylline and sitaxentan. Indeed, amphetamine derivatives also increase time run to exhaustion if combined with a pulmonary vasodilator. The vasodilators ambrisentan and bambuterol also prolong time run to exhaustion in rats if combined with a cardiac stimulant. The combination of theophylline and sitaxsentan reverses hypoxia‐induced blood pressure change in an anesthetized, hypoxic rat model. Theophylline does not increase vascular leak in exercising rats exposed to hypobaric hypoxia, indicating relative safety of the treatment. We demonstrate that the pairing of a cardiac stimulant with a pulmonary vasodilator provides synergism, compared to individual drugs. Other drug families therefore might be used interchangeably in this therapeutic approach. With preclinical data showing no toxicity, human studies are currently conducted to test the safety and efficacy of these drug combinations.