Geert Kleinnibbelink

Exercise-Induced Cardiac Function under Hypoxia 2 37 INTRODUCTION It is well established that exercise is associated with potent cardioprotective effects 1-3 , but acute exercise can lead to a paradoxical short-term increase in cardiac events. 4-6 One potential explanation is that exercise performed under demanding conditions (i.e. exercise at high-intensity and/or during prolonged duration) may lead to an acute reduction in cardiac function. 7-13 This transient decline in cardiac function after strenuous exercise is typically referred to as exercise-induced cardiac fatigue (EICF). EICF may affect both left (LV) and right ventricles (RV), with possibly a larger impact on the RV due to the disproportionately higher wall stress experienced by the RV relative to the LV during exercise. 11, 14, 15 Previous studies have demonstrated that hypoxia increases the demands on the cardiovascular system. 16 Specifically, acute exposure to hypoxia induces a decrease in systemic vascular resistance at rest, which may contribute to a decrease in LV afterload. 17, 18 In contrast, hypoxia leads to a resting increase in pulmonary artery resistance, and subsequently to an increase in pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP). 19 Exercise in normoxic conditions results in additional load challenges and an increased PAP secondary to the mismatch of elevated stroke volume to inadequate pulmonary vascular distension. 20 This is exacerbated when exercising in hypoxic conditions, leading to an even greater PAP and RV wall stress and potentially further increasing the risk of RV EICF. 19-23 To non-invasively examine right heart haemodynamics, studies have examined conventional andDoppler based echocardiographic indices at rest and during exercise. 24-26 Recently, the strain-area loop has been introduced assessing simultaneous structure and strain across the cardiac cycle. 5 Previously, we found that RV loop characteristics relate to PVR in patients with pulmonary arterial hypertension (PAH) whilst also demonstrating value in the assessment of EICF. 27, 28 Therefore, these non-invasive characteristics may provide additional insight in understanding exercise-induced changes in hypoxia. In view of this, the aim of this study, was to investigate the acute effects of a bout of high-intensity exercise under hypoxia versus normoxia in healthy individuals on right- and left-sided cardiac function and mechanics (i.e. longitudinal strain and strain-area