Abstract

Hypoxia is a pathophysiological condition associated with several responses at the cardiovascular, pulmonary and vascular levels, which may develop into chronic diseases. This is relevant in human populations exposed to high altitudes, in either chronic continuous (permanent inhabitants) or intermittent hypoxia (IH) (high-altitude workers, tourists and mountaineers). In Chile, it is estimated that 1,000,000 people live in highlands and more than 55,000 work in high-altitude shifts. IH is associated with the development of systemic hypertension and left ventricular dysfunction. At present, however, our understanding of the basic mechanisms linking IH and cardiovascular dysfunction is limited by the pathophysiological heterogeneity of hypoxic patients and the presence of multiple confounding and comorbid conditions, including obesity and previous cardiac impairments. Moreover, the great variety of responses ranges from nonclinical effects to severe pulmonary hypertension and life-threatening risks. Consequently, there is a serious need to develop experimental models to study the mechanisms involved in the cardiovascular responses to IH and the potential deleterious effects. Acute exposure to high altitudes has been shown to induce oxidative stress in healthy human lowlanders, as indicated by an increase in free radical formation. However, IH may induce ischemic preconditioning in some animal models. Therefore, pharmacological preconditioning strategies have acquired importance in the development of novel therapies. Compelling data show cardiovascular beneficial effects in consuming fatty acids highly present in fish, such as omega 3, docosahexaenoic acid (DHA 22:6 omega 3), and eicosapentaenoic acid (EPA 20:5 omega 3). These fatty acids regulate cell membrane physicochemical properties (i.e., fluidity, organization and permeability) that affect signaling pathways, with probable antioxidant and anti-inflammatory effects on cardiac and vascular tissue. Also, dietary omega 3 might induce a form of preconditioning, nutritional preconditioning, limiting hypoxic cardiac injury and myocardial infarction and endow cardioprotection as powerful as ischemic preconditioning. These mechanisms have been demonstrated in some clinical trials in coronary and heart failure patients. Consequently, it is desirable to explore the pharmacokinetic effects of omega 3 supplementation in human populations exposed to IH.