Right Ventricle and High Altitude

Abstract

At high altitude, as hypoxia induces pulmonary vasoconstriction and increases ipulmonary arterial pressure, right ventricular (RV) function will be affected. The right ventricular function may be affected directly by the hypoxaemic challenge or indirectly through a pressure overload due, in turn to changes in the pulmonary circulation. Both animal and human studies show that moderate or transient hypoxia results in adaptive changes in right ventricle that are reversible with re-exposure to normoxic conditions and RV dysfunction is mainly due to mechanical overload from the pulmonary circulation. When hypoxia is more severe or more prolonged, it may directly impact ventricular diastolic or systolic function through mechanisms that remain to be unraveled. Chronic exposure to hypoxia in high-altitude natives suffering from Monge's disease may lead to RV hypertrophy, RV failure and overall cardiac failure. The adrenergic system may be involved, as well as HIF, PKC or phospholamban. More studies using the latest imaging technology should give us a better understanding of RV systolic and diastolic function in humans exposed to altitude hypoxia including acute, chronic or chronic intermittent hypoxia.

Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors

“…The left ventricle does not seem to be affected, except for a low proportion of aortic dilation, which could also be explained by the hyperdynamic state of this model. The latter findings agree with a previous report regarding left ventricle changes under hypoxia (Richalet and Pichon, 2014 ).…”

“…Likewise, this study also shows a striking proportion of RVWT enlargement, suggesting that in the long term, almost all subjects experience RV remodeling and that an mPAP value of 25 mmHg would be sufficient to generate significant changes in the right heart. Whether this is merely an acclimatization response in this model of exposure that causes the RV to increase its performance as a consequence of its homeometric adaptation to afterload increase (Kolár and Ostádal, 1991 ; Naeije and Dedobbeleer, 2013 ; Richalet and Pichon, 2014 ) and/or ROS activation by hypoxia of AMP kinase proteins (Chen et al, 2012 ; Waypa et al, 2016 ) or other mechanisms remains to be elucidated. Additionally, a vascular hyperdynamic state triggered by adrenergic activation and autonomic system imbalance must be considered for exerting its influence on the above variables and possibly in RV dilation (Richalet and Pichon, 2014 ).…”

“…A complex series of pathophysiological and physiological mechanisms are responsible for the responses to hypoxia. The first described mechanism is hypoxic pulmonary vasoconstriction (HPV) (von Euler and Liljestrand, 1946 ), which is followed by several metabolic and molecular alterations, such as an imbalance between endothelial vasoconstrictors and vasodilators, reactive oxygen species (ROS) (Chen et al, 2012 ), and some associated factors, including insulin and asymmetric dimethylarginine (ADMA) (Richalet and Pichon, 2014 ; Lüneburg et al, 2016 ).…”

Long‐term chronic intermittent hypoxia: a particular form of chronic high‐altitude pulmonary hypertension

“…47 However, an imbalance among factors such as endothelial vasoconstrictors, vasodilators, reactive oxygen species, other molecules (e.g., insulin, asymmetric dimethylarginine (ADMA)), susceptibility, and genetic factors is clearly the cornerstone at the molecular level. 7,48,49 As has commonly been observed in the clinical setting, most responses are physiologically useful; however, in some cases, these beneficial responses are excessive and can be the source of a pathological response. The main examples of such cases are exaggerated polycythemia or CMS under chronic hypoxia and HPV leading to HAPH 12 (Fig.…”

Right Ventricular Response to Acute Hypoxia Exposure: A Systematic Review

“…Available studies that evaluated the effects of acute high-altitude exposure on the RV produced conflicting results (Naeije and Dedobbeleer, 2013 ; Richalet and Pichon, 2014 ). While some studies demonstrated an augmented RV function in response to acute hypoxia-induced afterload increase (Berger et al, 2018 ; Sareban et al, 2020 ), others found no change (Huez et al, 2005 ) or even an impaired RV function (Reichenberger et al, 2007 ; Hanaoka et al, 2011 ; Page et al, 2013 ).…”