Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep

2007 ◽  
Vol 102 (2) ◽  
pp. 658-664 ◽  
Author(s):  
Philip N. Ainslie ◽  
Katie Burgess ◽  
Prajan Subedi ◽  
Keith R. Burgess
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
High Altitude ◽  
Cerebral Autoregulation ◽  
Central Sleep Apnea ◽  
Cerebrovascular Reactivity ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Low Altitude ◽  
Dynamic Cerebral Autoregulation

We tested the hypothesis that, following exposure to high altitude, cerebrovascular reactivity to CO2 and cerebral autoregulation would be attenuated. Such alterations may predispose to central sleep apnea at high altitude by promoting changes in brain Pco2 and thus breathing stability. We measured middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound) and arterial blood pressure during wakefulness in conditions of eucapnia (room air), hypocapnia (voluntary hyperventilation), and hypercapnia (isooxic rebeathing), and also during non-rapid eye movement (stage 2) sleep at low altitude (1,400 m) and at high altitude (3,840 m) in five individuals. At each altitude, sleep was studied using full polysomnography, and resting arterial blood gases were obtained. During wakefulness and polysomnographic-monitored sleep, dynamic cerebral autoregulation and steady-state changes in MCAv in relation to changes in blood pressure were evaluated using transfer function analysis. High altitude was associated with an increase in central sleep apnea index (0.2 ± 0.4 to 20.7 ± 23.2 per hour) and an increase in mean blood pressure and cerebrovascular resistance during wakefulness and sleep. MCAv was unchanged during wakefulness, whereas there was a greater decrease during sleep at high altitude compared with low altitude (−9.1 ± 1.7 vs. −4.8 ± 0.7 cm/s; P < 0.05). At high altitude, compared with low altitude, the cerebrovascular reactivity to CO2 in the hypercapnic range was unchanged (5.5 ± 0.7 vs. 5.3 ± 0.7%/mmHg; P = 0.06), while it was lowered in the hypocapnic range (3.1 ± 0.7 vs. 1.9 ± 0.6%/mmHg; P < 0.05). Dynamic cerebral autoregulation was further reduced during sleep ( P < 0.05 vs. low altitude). Lowered cerebrovascular reactivity to CO2 and reduction in both dynamic cerebral autoregulation and MCAv during sleep at high altitude may be factors in the pathogenesis of breathing instability.

scholarly journals Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation?

2017 ◽  
Vol 123 (3) ◽  
pp. 558-566 ◽  
Author(s):  
Sam C. Barnes ◽  
Naomi Ball ◽  
Ronney B. Panerai ◽  
Thompson G. Robinson ◽  
Victoria J. Haunton
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Cerebral Autoregulation ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Significant Difference ◽  
Random Frequency ◽  
Dynamic Cerebral Autoregulation

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2, and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs ( P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs ( P = 0.856) or for each of the four recordings between the two visits ( P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs ( P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting. NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation.

scholarly journals Differentiating Dynamic Cerebral Autoregulation Across Vascular Territories

2021 ◽  
Vol 12 ◽  
Author(s):  
Navpreet Reehal ◽  
Stephanie Cummings ◽  
Michael T. Mullen ◽  
Wesley B. Baker ◽  
David Kung ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Flow Velocity ◽  
Cerebral Artery ◽  
Transcranial Doppler ◽  
Cerebral Autoregulation ◽  
Posterior Cerebral Artery ◽  
Function Analysis ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Dynamic Cerebral Autoregulation

Objective: Transcranial Doppler is commonly used to calculate cerebral autoregulation, but measurements are typically restricted to a single cerebral artery. In exploring topographic heterogeneity, this study reports the first thorough comparison of autoregulation in all major cerebral vessels.Methods: In forty healthy adults, flow velocity was monitored in the anterior, middle, and posterior cerebral arteries, and synchronized with arterial blood pressure. A transfer function analysis provided characteristics of autoregulation by quantifying the relationship between blood pressure and cerebral blood flow velocity.Results: Phase, which quantifies the time course of autoregulation, was similar in all vessels. Gain, which quantifies the magnitude of hemodynamic regulation, was lower in posterior cerebral artery, indicative of tighter regulation. However, after adjusting for baseline flow differences in each vascular territory, normalized gain was similar in all vessels.Conclusions: Discriminating dynamic cerebral autoregulation between cerebrovascular territories is feasible with a transcranial doppler based approach. In the posterior cerebral artery of healthy volunteers, absolute flow is more tightly regulated, but relative flow regulation is consistent across cerebrovascular territories.Significance: The methodology can be applied to focal disease states such as stroke or posterior reversible encephalopathy syndrome, in which the topographic distribution of autoregulation may be particularly critical.

scholarly journals Quantification of dynamic cerebral autoregulation and CO2 dynamic vasomotor reactivity impairment in essential hypertension

2020 ◽  
Vol 128 (2) ◽  
pp. 397-409
Author(s):  
Vasilis Z. Marmarelis ◽  
Dae C. Shin ◽  
Mareike Oesterreich ◽  
Martin Mueller
Keyword(s):  
Essential Hypertension ◽  
Cerebral Autoregulation ◽  
Input Output ◽  
Physiological Mechanisms ◽  
Control Subjects ◽  
Vasomotor Reactivity ◽  
Model Based ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Dynamic Cerebral Autoregulation

The study of dynamic cerebral autoregulation (DCA) in essential hypertension has received considerable attention because of its clinical importance. Several studies have examined the dynamic relationship between spontaneous beat-to-beat arterial blood pressure data and contemporaneous cerebral blood flow velocity measurements (obtained via transcranial Doppler at the middle cerebral arteries) in the form of a linear input-output model using transfer function analysis. This analysis is more reliable when the contemporaneous effects of changes in blood CO2 tension are also taken into account, because of the significant effects of CO2 dynamic vasomotor reactivity (DVR) upon cerebral flow. In this article, we extract such input-output predictive models from spontaneous time series hemodynamic data of 24 patients with essential hypertension and 20 normotensive control subjects under resting conditions, using the novel methodology of principal dynamic modes (PDMs) that achieves improved estimation accuracy over previous methods for relatively short and noisy data. The obtained data-based models are subsequently used to compute indexes and markers that quantify DCA and DVR in each subject or patient and therefore can be used to assess the effects of essential hypertension. These model-based DCA and DVR indexes were properly defined to capture the observed effects of DCA and VR and found to be significantly different ( P < 0.05) in the hypertensive patients. We also found significant differences between patients and control subjects in the relative contribution of three PDMs to the model output prediction, a finding that offers the prospect of identifying the physiological mechanisms affected by essential hypertension when the PDMs are interpreted in terms of specific physiological mechanisms. NEW & NOTEWORTHY This article presents novel model-based methodology for obtaining diagnostic indexes of dynamic cerebral autoregulation and dynamic vasomotor reactivity in hypertension.

scholarly journals Increasing cerebral blood flow reduces the severity of central sleep apnea at high altitude

2018 ◽  
Vol 124 (5) ◽  
pp. 1341-1348 ◽  
Author(s):  
Keith R. Burgess ◽  
Samuel J. E. Lucas ◽  
Katie M. E. Burgess ◽  
Kate E. Sprecher ◽  
Joseph Donnelly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sleep Apnea ◽  
Healthy Volunteers ◽  
High Altitude ◽  
Ventilatory Response ◽  
Central Sleep Apnea ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Central Chemoreceptors

Earlier studies have indicated an important role for cerebral blood flow in the pathophysiology of central sleep apnea (CSA) at high altitude, but were not decisive. To test the hypothesis that pharmacologically altering cerebral blood flow (CBF) without altering arterial blood gas (ABGs) values would alter the severity of CSA at high altitude, we studied 11 healthy volunteers (8M, 3F; 31 ± 7 yr) in a randomized placebo-controlled single-blind study at 5,050 m in Nepal. CBF was increased by intravenous (iv) acetazolamide (Az; 10 mg/kg) plus intravenous dobutamine (Dob) infusion (2–5 μg·kg−1·min−1) and reduced by oral indomethacin (Indo; 100 mg). ABG samples were collected and ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) were measured by rebreathing and steady-state techniques before and after drug/placebo. Duplex ultrasound of blood flow in the internal carotid and vertebral arteries was used to measure global CBF. The initial 3–4 h of sleep were recorded by full polysomnography. Intravenous Az + Dob increased global CBF by 37 ± 15% compared with placebo ( P < 0.001), whereas it was reduced by 21 ± 8% by oral Indo ( P < 0.001). ABGs and HVR were unchanged in both interventions. HCVR was reduced by 28% ± 43% ( P = 0.1) during intravenous Az ± Dob administration and was elevated by 23% ± 30% ( P = 0.05) by Indo. During intravenous Az + Dob, the CSA index fell from 140 ± 45 (control night) to 48 ± 37 events/h of sleep ( P < 0.001). Oral Indo had no significant effect on CSA. We conclude that increasing cerebral blood flow reduced the severity of CSA at high altitude; the likely mechanism is via a reduction in the background stimulation of central chemoreceptors.NEW & NOTEWORTHY This work is significant because it shows convincingly for the first time in healthy volunteers that increasing cerebral blood flow will reduce the severity of central sleep apnea in a high-altitude model, without the potentially confounding effects of altering partial pressure of arterial carbon dioxide or the ventilatory response to hypoxia. The proposed mechanism of action is that of increasing the removal of locally produced CO2from the central chemoreceptors, causing the reduction in hypercapnic ventilatory response, hence reducing loop gain.

Influence of sympathoexcitation at high altitude on cerebrovascular function and ventilatory control in humans

2012 ◽  
Vol 113 (7) ◽  
pp. 1058-1067 ◽  
Author(s):  
P. N. Ainslie ◽  
S. J. E. Lucas ◽  
J.-L. Fan ◽  
K. N. Thomas ◽  
J. D. Cotter ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
High Altitude ◽  
Function Analysis ◽  
Low Frequency ◽  
Cerebrovascular Reactivity ◽  
Adrenergic Blockade ◽  
Ventilatory Control ◽  
Phase Lead ◽  
Arterial Blood ◽  
Transfer Function Analysis

We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3–10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco2 and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated ( P < 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02–0.07 Hz) increased, and phase lead was reduced (all P < 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (−40 ± 23%; P < 0.01). In contrast, blockade at HA reduced low-frequency coherence (−26 ± 20%; P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238%; P < 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA ( P < 0.01), blockade increased it comparably at SL and HA (∼43–68%; P < 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced ( P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.

Dynamic cerebral autoregulation during brain activation paradigms

2005 ◽  
Vol 289 (3) ◽  
pp. H1202-H1208 ◽  
Author(s):  
Ronney B. Panerai ◽  
Michelle Moody ◽  
Penelope J. Eames ◽  
John F. Potter
Keyword(s):  
Transfer Function ◽  
Cerebral Autoregulation ◽  
Function Analysis ◽  
Brain Activation ◽  
Hemispheric Lateralization ◽  
Step Response ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
The Right ◽  
Dynamic Cerebral Autoregulation

Dynamic cerebral autoregulation (CA) describes the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (ABP). We tested the hypothesis that the efficiency of dynamic CA is increased by brain activation paradigms designed to induce hemispheric lateralization. CBF velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco2 were continuously recorded in 14 right-handed healthy subjects (21–43 yr of age), in the seated position, at rest and during 10 repeated presentations (30 s on-off) of a word generation test and a constructional puzzle. Nonstationarities were not found during rest or activation. Transfer function analysis of the ABP-CBFV (i.e., input-output) relation was performed for the 10 separate 51.2-s segments of data during activation and compared with baseline data. During activation, the coherence function below 0.05 Hz was significantly increased for the right MCA recordings for the puzzle tasks compared with baseline values (0.36 ± 0.16 vs. 0.26 ± 0.13, P < 0.05) and for the left MCA recordings for the word paradigm (0.48 ± 0.23 vs. 0.29 ± 0.16, P < 0.05). In the same frequency range, significant increases in gain were observed during the puzzle paradigm for the right (0.69 ± 0.37 vs. 0.46 ± 0.32 cm·s−1·mmHg−1, P < 0.05) and left (0.61 ± 0.29 vs. 0.45 ± 0.24 cm·s−1·mmHg−1, P < 0.05) hemispheres and during the word tasks for the left hemisphere (0.66 ± 0.31 vs. 0.39 ± 0.15 cm·s−1·mmHg−1, P < 0.01). Significant reductions in phase were observed during activation with the puzzle task for the right (−0.04 ± 1.01 vs. 0.80 ± 0.86 rad, P < 0.01) and left (0.11 ± 0.81 vs. 0.57 ± 0.51 rad, P < 0.05) hemispheres and with the word paradigm for the right hemisphere (0.05 ± 0.87 vs. 0.64 ± 0.59 rad, P < 0.05). Brain activation also led to changes in the temporal pattern of the CBFV step response. We conclude that transfer function analysis suggests important changes in dynamic CA during mental activation tasks.

scholarly journals Lack of correlation between cerebral vasomotor reactivity and dynamic cerebral autoregulation during stepwise increases in inspired CO2 concentration

2016 ◽  
Vol 120 (12) ◽  
pp. 1434-1441 ◽  
Author(s):  
Sung-Moon Jeong ◽  
Seon-Ok Kim ◽  
Darren S. DeLorey ◽  
Tony G. Babb ◽  
Benjamin D. Levine ◽  
...  
Keyword(s):  
Transfer Function ◽  
Cerebral Autoregulation ◽  
Function Analysis ◽  
Low Frequency ◽  
Frequency Range ◽  
Vasomotor Reactivity ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Cerebral Vasomotor Reactivity ◽  
Dynamic Cerebral Autoregulation

Cerebral vasomotor reactivity (CVMR) and dynamic cerebral autoregulation (CA) are measured extensively in clinical and research studies. However, the relationship between these measurements of cerebrovascular function is not well understood. In this study, we measured changes in cerebral blood flow velocity (CBFV) and arterial blood pressure (BP) in response to stepwise increases in inspired CO2 concentrations of 3 and 6% to assess CVMR and dynamic CA in 13 healthy young adults [2 women, 32 ± 9 (SD) yr]. CVMR was assessed as percentage changes in CBFV (CVMRCBFV) or cerebrovascular conductance index (CVCi, CVMRCVCi) in response to hypercapnia. Dynamic CA was estimated by performing transfer function analysis between spontaneous oscillations in BP and CBFV. Steady-state CBFV and CVCi both increased exponentially during hypercapnia; CVMRCBFV and CVMRCVCi were greater at 6% (3.85 ± 0.90 and 2.45 ± 0.79%/mmHg) than at 3% CO2 (2.09 ± 1.47 and 0.21 ± 1.56%/mmHg, P = 0.009 and 0.005, respectively). Furthermore, CVMRCBFV was greater than CVMRCVCi during either 3 or 6% CO2 ( P = 0.017 and P < 0.001, respectively). Transfer function gain and coherence increased in the very low frequency range (0.02-0.07 Hz), and phase decreased in the low-frequency range (0.07–0.20 Hz) when breathing 6%, but not 3% CO2. There were no correlations between the measurements of CVMR and dynamic CA. These findings demonstrated influences of inspired CO2 concentrations on assessment of CVMR and dynamic CA. The lack of correlation between CVMR and dynamic CA suggests that cerebrovascular responses to changes in arterial CO2 and BP are mediated by distinct regulatory mechanisms.

Dynamic cerebral autoregulation during and after handgrip exercise in humans

2010 ◽  
Vol 108 (6) ◽  
pp. 1701-1705 ◽  
Author(s):  
Shigehiko Ogoh ◽  
Kohei Sato ◽  
Toshinari Akimoto ◽  
Anna Oue ◽  
Ai Hirasawa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cerebral Autoregulation ◽  
Valsalva Maneuver ◽  
Maximum Voluntary Contraction ◽  
Static Exercise ◽  
Handgrip Exercise ◽  
Arterial Blood ◽  
Significant Difference ◽  
Acute Hypotension ◽  
Dynamic Cerebral Autoregulation

The purpose of the present study was to examine the effect of static exercise on dynamic cerebral autoregulation (CA). In nine healthy subjects at rest before, during, and after static handgrip exercise at 30% maximum voluntary contraction, the response to an acute drop in mean arterial blood pressure and middle cerebral artery mean blood velocity was examined. Acute hypotension was induced nonpharmacologically via rapid release of bilateral thigh occlusion cuffs. Subjects were instructed to avoid executing a Valsalva maneuver during handgrip. To quantify dynamic CA, the rate of regulation (RoR) was calculated from the change in cerebral vascular conductance index during the transient fall in blood pressure. There was no significant difference in RoR between rest (mean ± SE; 0.278 ± 0.052/s), exercise (0.333 ± 0.053/s), and recovery (0.305 ± 0.059/s) conditions ( P = 0.747). In addition, there was no significant difference in the rate of absolute cerebral vasodilatory response to acute hypotension between three conditions ( P = 0.737). This finding indicates that static exercise and related elevations in blood pressure do not alter dynamic CA.

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