Dynamic cerebral autoregulation during and following acute hypoxia: role of carbon dioxide

Abstract

Querido JS, Ainslie PN, Foster GE, Henderson WR, Halliwill JR, Ayas NT, Sheel AW. Dynamic cerebral autoregulation during and following acute hypoxia: role of carbon dioxide. J Appl Physiol 114: 1183-1190, 2013. First published March 7, 2013 doi:10.1152/japplphysiol.00024.2013.-Previous research has shown an inconsistent effect of hypoxia on dynamic cerebral autoregulation (dCA), which may be explained by concurrent CO2 control. To test the hypothesis that hypoxic dCA is mediated by CO2, we assessed dCA (transcranial Doppler) during and following acute normobaric isocapnic and poikilocapnic hypoxic exposures. On 2 separate days, the squat-stand maneuver was used to determine dCA in healthy subjects (n ϭ 8; 3 women) in isocapnic and poikilocapnic hypoxia exposures (end-tidal oxygen pressure 50 Torr for 20 min). In isocapnic hypoxia, the amplitude of the cerebral blood flow response to increases and decreases in mean arterial blood pressure were elevated (i.e., increases in gain of ϩ35 and ϩ28%, respectively; P Ͻ 0.05). However, dCA gain to increases in pressure was reduced compared with baseline (Ϫ32%, P Ͻ 0.05) following the isocapnic hypoxia exposure. Similarly, intravenous bolus injections of sodium nitroprusside and phenylephrine in a separate group of subjects (n ϭ 8; 4 women) also demonstrated a reduction in dCA gain to hypertension following isocapnic hypoxia. In contrast, dCA gain with the squat-stand maneuver did not significantly change from baseline during or following poikilocapnic hypoxia (P Ͼ 0.05). Our results demonstrate that dCA impairment in isocapnic hypoxia can be prevented with hypocapnia, and highlight the integrated nature of hypoxic cerebrovascular control, which is under strong CO2 influence. autonomic control; cerebral autoregulation; hypoxia; hypocapnia CEREBRAL AUTOREGULATION (CA) refers to the physiological mechanisms that maintain blood flow constant during steadystate (static CA) and abrupt [dynamic CA (dCA)] changes in blood pressure. The mechanisms of CA are complex and incompletely understood, but likely rely on a combination and interaction of myogenic, neural, endothelial, and metabolic factors (1, 32). Although recently challenged in both healthy humans (18) and patients (13), the conventional model of static CA proposes that cerebral blood flow (CBF) is independent of steady-state changes in mean arterial pressure (MAP) between ϳ50 and 160 mmHg (17). In contrast, dCA responds to sudden changes in blood pressure and is frequently active throughout a typical day, such as during rapid adjustments in posture. Early methods of dCA assessment in humans often included an abrupt decrease in blood pressure with rapid thigh-cuff deflation (1), whereas later assessments focused on transfer function analysis of spontaneous oscillations in blood pressure and CBF over both time and frequency domains (39). Although these methods have the advantage of being noninvasive and easily administered, they do not fully characterize dCA. Specifically, these methods do not differentiate the dCA respon...

Dynamic Cerebral Autoregulation Is Acutely Impaired During Maximal Apnoea In Trained Divers

“…Nevertheless, our findings are in agreement with the above reports, insofar as the trained divers who displayed the largest rise in PETCO 2 during maximal apnoea presented with the greatest impairment in dCA. It is wellestablished that isocapnic hypoxia impairs the cerebral autoregulatory response in awake, spontaneously breathing humans [19][20][21]. It is therefore surprising that we observed no direct relationship between the fall in PETO 2 and the rise in PhSI during maximal apnoea.…”

“…Previous studies indicate that the relationship between arterial CO 2 on cerebrovascular pressure-reactivity is nonlinear, primarily affecting the phase more so than the amplitude dynamics of the cerebral autoregulatory response [15][16][17][18]. Moreover, it is well-established that arterial O 2 tension exerts a modulatory effect on dCA, wherein arterial hypoxaemia seemingly impairs the autoregulatory response [19][20][21]. Consequently, dCA was assessed using phase synchronisation analysis [22,23] on spontaneous, beatto-beat values of mean arterial blood pressure (MAP) and middle cerebral artery blood flow-velocity (CBFV) during maximal apnoea.…”

End tidal-to-arterial CO2and O2gas gradients at low- and high-altitude during dynamic end-tidal forcing

“…Whereas feedback control is accomplished using a proportional and integral error reduction control system. This system has been used previously to control end-tidal gases during physiological stressors (1,14,32). End-tidal steady state was determined once values were within 1 mmHg of the desired target point for at least three consecutive breaths.…”

“…This system uses a mixture of three gases (O 2 , CO 2 , and N 2 ) to deliver the desired inspiratory gas volume into a 6-liter capacity reservoir bag. This DEF system has effectively controlled end-tidal gases independent of breathing frequency during isocapnic and poikilocapnic hypoxia (14,32) and during a hyperthermic intervention to correct marked hypocapnia (1).…”

Chemoreceptor Responsiveness at Sea Level Does Not Predict the Pulmonary Pressure Response to High Altitude

“…The isocapnic hypoxia was terminated when either: 1) partial pressure of end-tidal oxygen (P ET O 2 ) reached 45mmHg at SL; 2) ventilation (V E ) exceeded 100L/min; or 3) the participant reached the end of their tolerance. In the 2012 experiments, isocapnic hypoxia (P ET O 2 = 47mmHg) was maintained over 10 minutes via end-tidal forcing, as described in depth elsewhere 29,32 .…”