Cardiac adaptation to chronic high-altitude hypoxia: Beneficial and adverse effects

Abstract

This review deals with the capability of the heart to adapt to chronic hypoxia in animals exposed to either natural or simulated high altitude. From the broad spectrum of related issues, we focused on the development and reversibility of both beneficial and adverse adaptive myocardial changes. Particular attention was paid to cardioprotective effects of adaptation to chronic high-altitude hypoxia and their molecular mechanisms. Moreover, interspecies and age differences in the cardiac sensitivity to hypoxia-induced effects in various experimental models were emphasized.

Introduction

Chronic myocardial hypoxia as the result of disproportion between oxygen supply and demand at the tissue level may be induced by several mechanisms. The most common causes are undoubtedly (i) ischemic hypoxia (often described as “cardiac ischemia”), induced by the reduction or interruption of the coronary blood flow, and (ii) systemic (hypoxic) hypoxia, characterized by a drop in $P_{{\text{O}}_2}$ in the arterial blood but adequate perfusion. For the sake of completeness we could add (iii) anemic hypoxia, in which the arterial $P_{{\text{O}}_2}$ is normal but the oxygen transport capacity of the blood is decreased. In terms of relevant chronic clinical syndromes, ischemic hypoxia is manifested primarily in chronic ischemic heart disease whereas systemic hypoxia is associated with chronic cor pulmonale of varying origin, sleep apnea, cyanosis due to a hypoxemic congenital heart disease, and changes in the cardiopulmonary system induced by a decrease in barometric pressure at high altitude (Table 1). In two cases, however, systemic hypoxia can be considered as physiological: (i) the fetal myocardium adapted to hypoxia corresponding to an altitude of 8000 m and (ii) the myocardium of subjects living permanently at high altitudes. In both situations the myocardium is significantly more resistant to acute oxygen deficiency but in populations in lowlands this property is lost soon after birth (Moret, 1980, Heath and Williams, 1995).

Although the heart obviously has the capability to adapt to various forms of hypoxia, this review relates only to effects of chronic high-altitude hypoxia (HAH). From the broad spectrum of related problems we have concentrated on the development and regression of adaptive responses of the myocardium as they were described in experimental studies. Since most of the recent papers published on the different aspects of myocardial adaptation to HAH refer almost exclusively to studies published in the last few years, particular attention was paid to original reports on the discussed questions.