A change of heart: Mechanisms of cardiac adaptation toacute and chronic hypoxia

 Over the last 100 years, high-altitude researchers have amassed a comprehensiveunderstanding of the global cardiac responses to acute, prolonged and lifelong hypoxia.When lowlanders are exposed to hypoxia, the drop in arterial oxygen content demands anincrease in cardiac output, which is facilitated by an elevated heart rate at the same time asventricular volumes are maintained. As exposure is prolonged, haemoconcentration restoresarterial oxygen content, whereas left ventricular filling and stroke volume are lowered as a resultof a combination of reduced blood volume and hypoxic pulmonary vasoconstriction. Populationsnative to high-altitude, such as the Sherpa in Asia, exhibit unique lifelong or generationaladaptations to hypoxia. For example, they have smaller left ventricular volumes compared tolowlanders despite having larger total blood volume. More recent investigations have begunto explore the mechanisms underlying such adaptive responses by combining novel imagingtechniques with interventions that manipulate cardiac preload, afterload, and/or contractility.This work has revealed the contributions and interactions of (i) plasma volume constriction;(ii) sympathoexcitation; and (iii) hypoxic pulmonary vasoconstriction with respect to alteringcardiac loading, or otherwise preserving or enhancing biventricular systolic and diastolic functioneven amongst high altitude natives with excessive erythrocytosis. Despite these advances, variousareas of investigation remain understudied, including potential sex-related differences in responseto high altitude. Collectively, the available evidence supports the conclusion that the humanheart successfully adapts to hypoxia over the short- and long-term, without signs of myocardialdysfunction in healthy humans, except in very rare cases of maladaptation.