Ainslie PN, Hamlin M, Hellemans J, Rasmussen P, Ogoh S. Cerebral hypoperfusion during hypoxic exercise following two different hypoxic exposures: independence from changes in dynamic autoregulation and reactivity. Am J Physiol Regul Integr Comp Physiol 295: R1613-R1622, 2008. First published September 3, 2008 doi:10.1152/ajpregu.90420.2008.-We examined the effects of exposure to 10 -12 days intermittent hypercapnia [IHC: 5:5-min hypercapnia (inspired fraction of CO2 0.05)-to-normoxia for 90 min (n ϭ 10)], intermittent hypoxia [IH: 5:5-min hypoxia-to-normoxia for 90 min (n ϭ 11)] or 12 days of continuous hypoxia [CH: 1,560 m (n ϭ 7)], or both IH followed by CH on cardiorespiratory and cerebrovascular function during steady-state cycling exercise with and without hypoxia (inspired fraction of oxygen, 0.14). Cerebrovascular reactivity to CO2 was also monitored. During all procedures, ventilation, end-tidal gases, blood pressure, muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAv) were measured continuously. Dynamic cerebral autoregulation (CA) was assessed using transfer-function analysis. Hypoxic exercise resulted in increases in ventilation, hypocapnia, heart rate, and cardiac output when compared with normoxic exercise (P Ͻ 0.05); these responses were unchanged following IHC but were elevated following the IH and CH exposure (P Ͻ 0.05) with no between-intervention differences. Following IH and/or CH exposure, the greater hypocapnia during hypoxic exercise provoked a decrease in MCAv (P Ͻ 0.05 vs. preexposure) that was related to lowered cerebral oxygenation (r ϭ 0.54; P Ͻ 0.05). Following any intervention, during hypoxic exercise, the apparent impairment in CA, reflected in lowered low-frequency phase between MCAv and BP, and MCAv-CO2 reactivity, were unaltered. Conversely, during hypoxic exercise following both IH and/or CH, there was less of a decrease in muscle oxygenation (P Ͻ 0.05 vs. preexposure). Thus IH or CH induces some adaptation at the muscle level and lowers MCAv and cerebral oxygenation during hypoxic exercise, potentially mediated by the greater hypocapnia, rather than a compromise in CA or MCAv reactivity. hypoxia; exercise; intermittent and continuous hypoxia; cerebral blood flow ELEVATIONS IN VENTILATORY sensitivity to hypoxia following exposure to either continuous hypoxia [CH, e.g., high altitude (7, 35)] or intermittent hypoxia [IH (11,20,28,42)] results in subsequent hypocapnia (i.e., reduction in end-tidal CO 2 ). Because hypocapnia results in cerebral vasoconstriction (23,32), elevations in ventilatory chemosensitivity may result in cerebral hypoperfusion. During normoxic exercise, ventilatory chemosensitivity is only one of multiple signals that integrate to increase ventilation (45); however, following exposure to IH, an enhanced chemosensitivity activation was evident during hypoxic exercise (21). Although cerebral perfusion was not monitored in that study (21), it seems reasonable to speculate that an enhanced ventilato...