[Show abstract][Hide abstract] ABSTRACT: Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n = 50 rest; n = 20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures.
These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.
Medical Engineering & Physics 01/2015; in press:2014. · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA.
Methods: In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2-1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21).
Results: Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=<0.05; P>0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07).
Conclusion: We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA.
[Show abstract][Hide abstract] ABSTRACT: Cerebrovascular reactivity impacts CO2/[H+] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system, which perfuses the brainstem. We hypothesized that: 1) posterior versus anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and 2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End-tidal forcing was used to induce steady-state hyperoxic (300 mmHg PETO2) hypercapnia (+3, +6 and +9 mmHg PETCO2) and isocapnic hypoxia (45 mmHg PETO2) before and following pharmacological blunting (Indomethacin; INDO; 1.45±0.17 mg/kg) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra-cranial arterial blood velocities and extra-cranial blood flows were measured during these challenges. INDO-induced blunting of cerebrovascular flow responsiveness (CVR) to CO2 was unrelated to variability in ventilatory sensitivity during hyperoxic hypercapnia. Further results in a sub-group of volunteers (n = 9) revealed that elevations of PETCO2 via end-tidal forcing reduce arterial-jugular venous gradients, attenuating the effect of CBF on chemoreflex responses. During isocapnic hypoxia, vertebral artery CVR was related to the magnitude of HVD (R2 = 0.27; P<0.04; n = 16), suggesting that CO2/[H+] washout from central chemoreceptors modulates hypoxic ventilatory dynamics. No relationships were apparent with anterior CVR. As higher posterior, but not anterior, CVR was linked to HVD, our study highlights the importance of measuring flow in posterior vessels to investigate CBF and ventilatory integration.This article is protected by copyright. All rights reserved
The Journal of Physiology 12/2014; · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monitoring cerebral blood flow (CBF) and oxygenation has implications for both clinical practice and research interests; e.g., to provide insight into functional neurovascular coupling, to better understand orthostatic hypotension, and to evaluate the influence of vasopressors on cerebral oxygenation during anes-thesia and/or surgery. These topics, and others, are addressed in this e-book by presenting original research, reviews, and opin-ion papers covering new, exciting but also controversial issues related to cerebral oxygenation in health and disease as evaluated by near-infrared spectroscopy (NIRS). There is interest in the impact of vasopressors on the NIRS-determined frontal lobe oxygenation (S c O 2). For example, a reduction in S c O 2 is reported with use of phenylephrine and noradrenaline at rest in healthy subjects, during anesthesia in non-cardiac and cardiac patients and during cardiopulmonary bypass in diabetics. However, possible extracranial contami-nation of the NIRS signal, especially with the utilization of vasopressors, challenges these conclusions. Keeping this limi-tation in mind, Foss et al. (2014) explored the influence of phenylephrine and ephedrine, on S c O 2 during cesarean sec-tion with spinal anesthesia. Both vasopressors were effective at maintaining mean arterial pressure (MAP). Still, phenyle-phrine was the agent associated with a reduction in S c O 2 . In addition, Kitchen et al. (2014) studied the effect of calcium chloride compared to α-and β-adrenergic receptor agonists (ephedrine, phenylephrine, adrenaline, or noradrenaline) follow-ing anesthesia-induced hypotension in patients scheduled for major abdominal surgery. This case series suggested that S c O 2 was preserved in patients who received calcium chloride, as well as β-adrenergic receptor agonists, but slightly reduced (2%) in those who received α-adrenergic drugs. Also, ventilation, O 2 supplementation and body position have the potential to affect NIRS-derived S c O 2 during surgery. Larsen et al. (2014) explored whether induction of anesthesia in the reclining, compared to sitting beach-chair position, secures cere-brovascular hemodynamics, including S c O 2 . S c O 2 was found to be higher, combined with more stable hemodynamics, character-ized by a reduced utilization of ephedrine, following induction of anesthesia in the reclining beach-chair vs. the sitting posi-tion. In their retrospective analyses of patients undergoing liver transplantation, Sørensen et al. (2014) report that S c O 2 changes during surgery were closely related to those in end-tidal carbon dioxide tension. In order to ensure stability in S c O 2 during the different phases of a liver transplantation, a varying ventilatory strategy may be needed to reduce the incidence of postoper-ative complications. Rokamp et al. (2014a) examined whether O 2 supplementation could maintain S c O 2 and skeletal muscle oxygenation in vascular surgical patients. These authors con-clude that O 2 supplementation indeed elevates S c O 2 and skele-tal muscle oxygenation in these patients during surgery but does not seem to sufficiently prevent a critical reduction in S c O 2 . Nielsen (2014) reviewed the impact of different surgeries on S c O 2 . His report indicates that the impact of non-cardiac surgery on S c O 2 is highly variable and in some types of surgery, cerebral desaturation may be related to postoperative cognitive dysfunction. Arterial pressure influences CBF. However, the role of arterial pressure variability on clinical outcome is not clear. Bronzwaer et al. (2014) explored the relationship between arterial pres-sure variations, stroke volume index and regional cerebral per-fusion during transient central blood volume depletion and repletion in healthy volunteers and found that middle cere-bral artery flow velocity (MCA Vmean) is related linearly to arterial pressure variability in subjects under these conditions. In their review, Rickards and Tzeng (2014) tried to recon-cile two apparently discrepant views regarding variability in arterial pressure and CBF (negative vs. positive impact on clinical outcome), and suggest that the time scale of hemo-dynamic variability, that is short time variability vs. longer term fluctuations, may be the key to merge these divergent views. To better understand the integrative components of cere-brovascular control, and thus oxygenation, during hyperthermia, Bain et al. (2014) discuss the mechanisms related to CBF and oxygenation changes during moderate to severe levels of hyper-thermia. On the opposite spectrum, a reduction in cerebral temperature (hypothermia) may be important, for example to prevent cerebral ischemia during anesthesia or to improve neu-rological outcome and survival after cardiac arrest. Nybo et al. (2014) explored the impact of different means of brain cooling on cerebral temperature balance and oxygenation, namely intranasal cooling, percutaneous cooling of the carotid arteries and nasal ventilation. Other physiological challenges influence CBF and oxygena-tion. Rokamp et al. (2014b) explored whether cholinergic vasodi-latation is of importance for the elevation in regional CBF, measured by arterial spin labeling and blood O 2 level depen-dent functional magnetic resonance imaging during a handgrip
[Show abstract][Hide abstract] ABSTRACT: The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and cardiorespiratory metrics were measured during maximum dry apneas in elite breath-hold divers (n=17). To isolate the effects of apnea and IBM from the concurrent changes on ABG, end-tidal forcing ('clamp') was then used to replicate an identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23 to 37 mm Hg (30±7 mm Hg). Elevation in mean arterial pressure was greater during apnea than during clamp reaching +54±24% versus 34±26%, respectively; however, CBF increased similarly between apnea and clamp (93.6±28% and 83.4±38%, respectively). This latter observation indicates that during the overall apnea period IBM per se do not augment CBF and that the brain remains sufficiently protected against hypertension. Termination of apnea was not determined by reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial oxygen content, oxygen delivery was maintained by commensurately increased CBF.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 November 2014; doi:10.1038/jcbfm.2014.170.
[Show abstract][Hide abstract] ABSTRACT: Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times-a-day for 48 h) to prevent increases in PASP, and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ+HCO3−) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, [HCO3−], and PaCO2. AZ decreased pH (-0.08 ± 0.01), [HCO3−] (-7.1 ± 0.7 mmol/l), and PaCO2 (-4.5 ± 1.4 mmHg; p<0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (p<0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (p<0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (p<0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or PaCO2.This article is protected by copyright. All rights reserved
The Journal of Physiology 11/2014; · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.
[Show abstract][Hide abstract] ABSTRACT: The incidence of vasovagal syncope is more common in the morning. Previous researchers have reported negligible diurnal variation in the physiological responses associated with initial orthostatic hypotension (IOH). Nevertheless, physical activity and sleep prior to morning and afternoon test times have not been controlled and may influence the findings. We designed a semi-constant routine protocol to examine diurnal variation in cardiorespiratory and cerebrovascular responses to active standing.
[Show abstract][Hide abstract] ABSTRACT: Both short-term and life-long high altitude (HA) exposure challenge the cardiovascular system to meet the metabolic demand for oxygen (O2) in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimise myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in HA Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest, and discuss the potential consequences for exercise capacity. Collectively, data indicate chronic structural ventricular adaptation, with adult Sherpa having smaller absolute and relative LV size. Consistent with structural remodelling, cardiac mechanics also differ in Sherpa when compared to lowlanders at HA. These differences are characterised by a reduction in resting systolic deformation and slower diastolic untwisting, a surrogate of relaxation. These changes may reflect a functional cardiac adaptation that affords Sherpa the same mechanical reserve seen in lowlanders at sea level, which is absent when they ascend to HA.This article is protected by copyright. All rights reserved
[Show abstract][Hide abstract] ABSTRACT: Introduction
Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF.
The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n = 28); therefore, CBF was also adjusted to account for small changes in PaCO2.
The linear regression coefficient between MAP and CBF (or velocity) of 0.82 ± 0.77%ΔCBF/%ΔMAP during decreases in MAP (n = 23 experiments) was significantly different than the relationship of 0.21 ± 0.47%ΔCBF/%ΔMAP during increases (n = 26 experiments; p < 0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64 ± 1.16%ΔCBF/%ΔMAP (n = 16) and 0.39 ± 0.30%ΔCBF/%ΔMAP (n = 12) for increased vs. decreased MAP changes, respectively (p = 0.60).
The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2.
Medical Engineering & Physics 09/2014; · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined two novel hypotheses: 1) That orthostatic tolerance (OT) would be prolonged when hyperventilatory-induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and 2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the “CBF reserve”, and ultimately reduce OT. In Study 1 (n = 24; aged 25±4 y) participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope; end-tidal carbon dioxide (PETCO2) was clamped at baseline levels (isocapnic trial) or uncontrolled. In Study 2 (n = 10; aged 25±4 y), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.2 mg/kg) or unaltered (placebo) followed by LBNP to pre-syncope. Beat-by-beat measurements of middle cerebral artery blood flow velocity (MCAv; transcranial Doppler), heart rate (ECG), blood pressure (BP; Finometer) and end-tidal gases were obtained continuously. In a subset of subjects’ arterial-to-jugular venous differences were obtained to examine the independent impact of hypocapnia or cerebral hypoperfusion (following INDO) on cerebral oxygen delivery and extraction. Study 1: During the isocapnic trial, PETCO2 was successfully clamped at baseline levels at pre-syncope (38.3±2.7 vs. 38.5±2.5 mm Hg respectively; P = 0.50). In the uncontrolled trial, PETCO2 at pre-syncope was reduced by 10.9±3.9 mm Hg (P≤0.001). Compared to the isocapnic trial, the decline in mean MCAv was 15±4 cm∙s−1 (35%; P≤0.001) greater in the uncontrolled trial, yet the time to pre-syncope was comparable between trials (544±130 v 572±180 s; P = 0.30). Study 2: Compared to placebo, INDO reduced resting MCAv by 19±4 cm∙s−1 (31%; P≤0.001), but time to pre-syncope remained similar between trials (placebo: 1123±138 vs. INDO: 1175±212 s; P = 0.53). The brain extracted more oxygen in face of hypocapnia (34% to 53%) or cerebral hypoperfusion (34% to 57%) to compensate for reductions in delivery. In summary, cerebral hypoperfusion either at rest or induced by hypocapnia at pre-syncope does not impact OT, likely due to a compensatory increase in oxygen extraction.This article is protected by copyright. All rights reserved
The Journal of Physiology 09/2014; · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cerebral blood flow responses to transient blood pressure challenges are frequently attributed to cerebral autoregulation (CA) yet accumulating evidence indicates vascular properties like compliance are also influential. We hypothesized that middle cerebral blood velocity (MCAv) dynamics during or following a transient blood pressure perturbation can be accurately explained by the Windkessel mechanism. Eighteen volunteers underwent blood pressure manipulations including bilateral thigh cuff deflation (TC) and sit-to-stand (STS) maneuvers under normocapnic and hypercapnic (5% CO2) conditions. Pressure-flow recordings were analyzed using a Windkessel analysis approach that partitions the frequency-dependent resistance and compliance contributions to MCAv dynamics. The Windkessel was typically able to explain more than 50% of the MCAv variance as indicated by R2 values for both the flow recovery and post recovery phase. The most consistent predictors of MCAv dynamics under the control condition were the Windkessel capacitive gain and high frequency resistive gain. However, there were significant inter-individual variations in the composition of Windkessel predictors. Hypercapnia consistently reduced the capacitive gain and enhanced the low frequency (0.04-0.20 Hz) resistive gain for both TC and STS trials. These findings indicate that: 1) MCAv dynamics during acute transient hypotension challenges are dominated by cerebrovascular Windkessel properties independent of CA; 2) there is significant heterogeneity in Windkessel properties between individuals; and 3) hemodynamic effects of hypercapnia during transient blood pressure challenges primarily reflect changes in Windkessel properties rather than pure CA impairment.
Journal of Applied Physiology 08/2014; · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Ainslie, Philip N., and Andrew W. Subudhi. Invited Review: Cerebral blood flow at high altitude. High Alt Med Biol. 15:133-140, 2014.-This brief review traces the last 50 years of research related to cerebral blood flow (CBF) in humans exposed to high altitude. The increase in CBF within the first 12 hours at high altitude and its return to near sea level values after 3-5 days of acclimatization was first documented with use of the Kety-Schmidt technique in 1964. The degree of change in CBF at high altitude is influenced by many variables, including arterial oxygen and carbon dioxide tensions, oxygen content, cerebral spinal fluid pH, and hematocrit, but can be collectively summarized in terms of the relative strengths of four key integrated reflexes: 1) hypoxic cerebral vasodilatation; 2) hypocapnic cerebral vasoconstriction; 3) hypoxic ventilatory response; and 4) hypercapnic ventilatory response. Understanding the mechanisms underlying these reflexes and their interactions with one another is critical to advance our understanding of global and regional CBF regulation. Whether high altitude populations exhibit cerebrovascular adaptations to chronic levels of hypoxia or if changes in CBF are related to the development of acute mountain sickness are currently unknown; yet overall, the integrated CBF response to high altitude appears to be sufficient to meet the brain's large and consistent demand for oxygen. This short review is organized as follows: An historical overview of the earliest CBF measurements collected at high altitude introduces a summary of reported CBF changes at altitude over the last 50 years in both lowlanders and high-altitude natives. The most tenable candidate mechanism(s) regulating CBF at altitude are summarized with a focus on available data in humans, and a role for these mechanisms in the pathophysiology of AMS is considered. Finally, suggestions for future directions are provided.
High Altitude Medicine & Biology 06/2014; 15(2):133-40. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Short-term high altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly-adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodelling, we studied ventricular structure and function in Sherpa at 5050 m (n=11; 31±13 y, mass 68±10 kg, height 169±6 cm) and lowlanders at sea level (SL) and following 10±3 d at 5050 m (n=9; 34±7 y, mass 82±10 kg, height 177±6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders when compared to lowlanders at SL (both P<0.05). Sherpa had smaller right ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P<0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic untwisting velocity was significantly lower in Sherpa when compared to lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in RV end-diastolic area, however both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose this was consequent to a persistently higher PASP. In contrast to the RV, remodelling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodelling of systolic and diastolic LV function.
Journal of Applied Physiology 05/2014; · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the hypothesis that changes in the cerebrovascular resistance index (CVRi), independent of blood pressure (BP), will influence the dynamic relationship between blood pressure and cerebral blood flow in humans. We altered CVRi with (via controlled hyperventilation) and without (via Indomethacin (INDO; 1.2 mg/kg) changes in PaCO2. Sixteen subjects (12 male, 27±7yrs) were tested on two occasions (INDO and hypocapnia) separated by >48hr. Each test incorporated seated rest (5-min), followed by squat-stand maneuvers to increase BP variability and improve assessment of the pressure-flow dynamics using linear transfer function analysis (TFA). Beat-to-beat BP, middle cerebral artery (MCAv), posterior cerebral artery (PCAv) velocity and end-tidal PCO2 were monitored. Dynamic pressure-flow relations were quantified using TFA between BP and MCAv/PCAv in the very low and low frequencies through the driven squat-stand maneuvers at 0.05 and 0.10 Hz. MCAv and PCAv reductions by INDO and hypocapnia were well-matched and CVRi was comparably elevated (P<0.001). During the squat-stand maneuvers (0.05 and 0.10 Hz), the point estimates of absolute gain were universally reduced and phase was increased under both conditions. In addition to an absence of regional differences, our findings indicate that alterations in CVRi independent of PaCO2 can alter cerebral pressure-flow dynamics. These findings are consistent with the concept of CVRi being a key factor that should be considered in the correct interpretation of cerebral pressure-flow dynamics as indexed using TFA metrics.
Journal of Applied Physiology 04/2014; · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures. These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.
Medical Engineering & Physics 04/2014; · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The arterial baroreflex is critical to both short and long-term regulation of blood pressure. However, human baroreflex research has been largely limited to the association between blood pressure and cardiac period (or heart rate) or indices of vascular sympathetic function. Over the past decade, emerging techniques based on carotid ultrasound imaging have allowed new means of understanding and measuring the baroreflex. In this review, we describe the assessment of the mechanical and neural components of the baroreflex through the use of carotid ultrasound imaging. The mechanical component refers to the change in carotid artery diameter in response to changes in arterial pressure, and the neural component refers to the change in R-R interval (cardiac baroreflex) or muscle sympathetic nerve activity (sympathetic baroreflex) in response to this barosensory vessel stretch. The key analytical concepts and techniques are discussed, with a focus on the assessment of baroreflex sensitivity via the modified Oxford method. We illustrate how the application of carotid ultrasound imaging has contributed to a greater understanding of baroreflex physiology in humans, covering topics such as ageing and diurnal variation, and physiological challenges including exercise, postural changes and mental stress.This article is protected by copyright. All rights reserved.