Ergogenic effects and potential synergism of combined doxapram and acetazolamide in hypoxic rats
Abstract
Hypoxemia is a potentially life‐threatening condition that can arise from various conditions, but there is a general lack of effective acute treatments. Voluntary increase of breathing frequency can increase blood oxgen concentrations, however, this does not work during sleep or unconsciousness. Pharmaceutical enhancement of breathing rates is available, but confounded by severe side effects related to respiratory alkalosis. We hypothesized that the addition of a mildly acidifying drug, such as acetazolamide, would be feasible and beneficial, if combined with a respiratory stimulant, such as doxapram. To test the hypothesis, we measured the ability of rats to run in a hypobaric athmosphere of approx. 4,267m/10% O2, after drug injection. Both high (20 mg/kg) and low (10 mg/kg) concentrations of doxapram significantly increased exercising endurance in rats (Log rank test, using a forced exercise wheel model, with or without acetazolamide (5/20 mg/kg) present. Neither low or high acetazolamide improved hypoxic exercise capacity. In an awake hemodynamic rat model, we found that acetazolamide decreased blood pH by approx. 0.05, and doxapram increased it by 0.03 pH points, however, subsequent injection of the respectively other drug normalized blood pH to a common level within 90 minutes. Although both drugs increased blood pO2 independent of each other, addition of the respective other drug did not induce any further increase in pO2. None of the drugs significantly changed pCO2. We conclude that the combination of doxapram and acetazolamide are potentially safe and efficacious in counteracting hypoxemia in rats, caused by hypoxic environments or other factors. Because they cancel out each others effects on blood pH, they might synergize in their ergogenicity of counteracting hypoxemia.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2018
- Source ID
- 10.1096/fasebj.2018.32.1_supplement.lb263
Entities
People
- David Irwin
- Karyn Hamilton
- Thies Schroeder
Organizations
- Colorado State University
- Defense Advanced Research Projects Agency
- Johannes Gutenberg University Mainz
- University of Colorado Denver