This article is a review of the rationale and methodology of a translational study conducted at altitude investigating the potential role of nitrate supplements to improve tolerance to hypoxia, and a discussion of the applicability of the findings to intensive care medicine.
GrocottMRichardsonAMontgomeryHMythenM. Caudwell Xtreme Everest: a field study of human adaptation to hypoxia. Crit Care2007;11: 151.
2.
LeachRMTreacherDF. ABC of oxygen: oxygen transport 2. Tissue hypoxia. BMJ1998;317: 1370–73.
3.
KumarV. Robbins and Cotran's pathologic basis of disease.8th ednKumarVAbbasAKAsterJ, eds. Saunders; London: 2010.
4.
HayesMATimminsACYauEH. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med1994;330: 1717–22.
5.
MartinDWindsorJ. From mountain to bedside: understanding the clinical relevance of human acclimatisation to high-altitude hypoxia. Postgrad Med J2008;84: 622–27.
6.
InceC. Review: The microcirculation is the motor of sepsis. Crit Care2005;9 (suppl4): S13–S19.
7.
GrocottMMontgomeryHVercueilA. High-altitude physiology and pathophysiology: implications and relevance for intensive care medicine. Crit Care2007;11: 203.
8.
MartinDSGoedhartPVercueilA. Changes in sublingual microcirculation flow index and vessel density on ascent to altitude. Exp Physiol2010;95: 880–91.
9.
LevettDZFernandezBORileyHL. The role of nitrogen oxides in human adaptation to hypoxia. Scientific Reports2011;1: 109.
10.
GrocottMMontgomeryH. Genetophysiology: using genetic strategies to explore hypoxic adaptation. High Alt Med Biol2008;9: 123–29.
11.
ThompsonJRaittJHutchingsL. Angiotensin-converting enzyme genotype and successful ascent to extreme altitude. High Alt Med Biol2007;8: 278–85.
12.
BeallCMLaskowskiDStrohlKP. Pulmonary nitric oxide in mountain dwellers. Nature2001;414: 411–12.
13.
ChenQHGeRLWangXZ. Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300m. J Appl Physiol1997;83: 661–67.
14.
KayserBWuT. High altitude adaptation in Tibetans. High Alt Med Biol2006;7: 193–208.
15.
ErzurumSCGhoshSJanochaAJ. Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans. Proc Natl Acad Sci USA2007;104: 17593–98.
16.
WeitzbergEHezelMLundbergJO. Nitrate-nitrite-nitric oxide pathway: implications for anesthesiology and intensive care. Anesthesiology2010;13: 1460–75.
17.
ButlerARFeelischM. Therapeutic uses of inorganic nitrite and nitrate: from the past to the future. Circulation2008;117: 2151–59.
18.
LundbergJOGladwinMTAhluwaliaA. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol2009;5: 865–69.
19.
KozlovAVStaniekKNohlH. Nitrite reductase activity is a novel function of mammalian mitochondria. FEBS Lett1999;454: 127–30.
20.
LundbergJOGovoniM. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med2004;37: 395–400.
21.
GeRLChenQHWangLHGenDYangP. Higher exercise performance and lower VO2 max in Tibetan than Han residents at 4,700m altitude. J Appl Physiol1994;77: 684–691.
22.
LarsenFJWeitzbergELundbergJOEkblomB. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med2010;48: 342–47.
23.
BaileySJFulfordJVanhataloA. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol2010;109: 135–48.
24.
LarsenFJWeitzbergELundbergJOEkblomB. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf)2007;191: 59–66.
25.
ShivaSGladwinMT. The ligand binding battle at cytochrome c oxidase: how NO regulates oxygen gradients in tissue. Circ Res2009;104: 1136–38.
