Effects of cardiorespiratory fitness on cerebrovascular regulation: responses to exercise changes in end-tidal PCO2 and intravenous infusion of sodium nitroprusside in elite athletes and sedentary volunteers

Bibliography: p. 114-13

Effects of Exposure to Intermittent Hypoxia on Oxidative Stress and Acute Hypoxic Ventilatory Response in Humans

International audienc

Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n=9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day-1, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (PET,O2) 88 Torr, nadir PET,O2 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (VT) increased, respiratory frequency remained unchanged, and minute ventilation (V′E) was increased. There was a negative correlation between EPO and sEPOR (r= -0.261; p=0.05), and between sEPOR and VT (r= -0.331; p=0.02). EPO was positively correlated with V′E (r=0.458; p=0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO

Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir = 45.0 mmHg) alternating with 2 min of normoxia (peak = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA