[Show abstract][Hide abstract] ABSTRACT: High-altitude exposure challenges the cardiovascular system to maintain oxygen delivery to the mitochondria under conditions of hypoxic stress. Following acclimatisation (3-5 days), stroke volume (SV) falls to below sea-level values but heart rate remains elevated, such that cardiac output is maintained compared to sea level. The decrease in SV has been a topic of research for over 40 years, but the underlying mechanisms are incompletely understood. Impaired systolic contractile function secondary to reduced coronary arterial oxygen tension has been investigated as a potential cause for the decrease in SV. However, despite in vitro evidence of impaired cardiac contractile force in severe hypoxia, the majority of studies to date have reported enhanced in vivo ventricular systolic function at rest and during exercise in humans up to and above 5000 m. However, the elevated function observed at rest has recently been suggested to reduce the functional reserve available during exercise. While in vivo systolic function appears enhanced at high altitude, a decrease in left ventricular end-diastolic volume (EDV) and altered filling patterns of both ventricles has been observed. The reduction in ventricular filling will undoubtedly affect SV, and four potential mechanisms have been proposed to explain the reduction in left ventricular filling. In this article, both historical and recent reports of systolic function at high altitude will be reviewed, and evidence supporting and refuting each of the four mechanisms underpinning reduced left ventricular filling will be discussed.
[Show abstract][Hide abstract] ABSTRACT: This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced peripheral resistance secondary to skin vasodilatation. Therefore, when hyperthermia is combined with conditions that increase cardiovascular strain, for example, orthostasis or dehydration, the inability to preserve cerebral perfusion pressure further reduces CBF. A reduced cerebral perfusion pressure is in turn the primary mechanism for impaired tolerance to orthostatic challenges. Any reduction in CBF attenuates the brain's convective heat loss, while the hyperthermic-induced increase in metabolic rate increases the cerebral heat gain. This paradoxical uncoupling of CBF to metabolism increases brain temperature, and potentiates a condition whereby cerebral oxygenation may be compromised. With levels of experimentally viable passive hyperthermia (up to 39.5-40.0 °C core temperature), the associated reduction in CBF (∼ 30%) and increase in cerebral metabolic demand (∼ 10%) is likely compensated by increases in cerebral oxygen extraction. However, severe increases in whole-body and brain temperature may increase blood-brain barrier permeability, potentially leading to cerebral vasogenic edema. The cerebrovascular challenges associated with hyperthermia are of paramount importance for populations with compromised thermoregulatory control--for example, spinal cord injury, elderly, and those with preexisting cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: Following exercise a reduction in mean arterial pressure (MAP) is often experienced and is referred to as post-exercise hypotension (PEH). Whilst syncope is more likely following exercise, it is unknown whether orthostatic tolerance is impacted by any exercise-intensity mediated effect on PEH. We examined the effect of exercise intensity on time to presyncope, induced via combined head-up tilt and lower body negative pressure following one-hour cycling at 30 and 70% of heart rate range (HRR). Healthy participants (n = 8, mean±SD: 28 ± 5 y) completed orthostatic testing to presyncope before and following exercise. Beat-to-beat middle cerebral artery blood flow velocity (MCAv), MAP and cerebral oxygenation (NIRS) were recorded continuously throughout orthostatic testing. During exercise, heart rates were 95 ± 6 and 147 ± 5 b∙min(-1) for 30% and 70% HRR, respectively, with average power outputs 103 ± 22 and 221 ± 45 watts, respectively. Time to presyncope occurred 32% faster following the 70% HRR trial (952 ± 484 s vs. 1418 ± 435 s, p = 0.004). Both before and following exercise, presyncope occurred at the same reduction in MCAv (grouped mean -30 ± 11 cm∙s(-1) ), MAP (-18 ± 13 mm Hg), total oxygenation index (-6 ± 2%) and partial pressure of end tidal CO2 (PET CO2 , -16 ± 8 mm Hg, all P > 0.1). At presyncope following exercise the MCAv response was related more to the change in PET CO2 from the baseline preceding orthostatic testing (R(2) = 0.50, P = 0.01) than to the hypotension (R(2) = 0.12, P = 0.17). Presyncope both before and following exercise occurred as a result of the same physiological perturbations, albeit greatly accelerated following more intense exercise. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: We examined the impact of progressive hypotension with and without hypocapnia on regional extracranial cerebral blood flow and intra-cranial velocities. Participants underwent progressive lower-body negative pressure until pre-syncope to inflict hypotension. End-tidal carbon dioxide was clamped at baseline levels (isocapnic trial) or uncontrolled (poikilocapnic trial). Middle and posterior cerebral artery blood velocities (transcranial Doppler), heart rate, blood pressure and end-tidal carbon dioxide were obtained continuously. Measurements of internal carotid artery and vertebral artery blood flow were also obtained. Overall, blood pressure was reduced by ~20% from baseline in both trials (P<0.001). In the isocapnic trial, end-tidal carbon dioxide was successfully clamped at baseline with hypotension, whereas in the poikilocapnic trial it was reduced by 11.1 mm Hg (P<0.001) with hypotension. The decline in the internal carotid artery blood-flow with hypotension was comparable between trials (-139 ± 82 ml; ~30%; P<0.0001); however, the decline in the vertebral artery blood flow was -28 ± 22 ml/min (~21%) greater in the poikilocapnic trial compared with the isocapnic trial (P=0.002). Regardless of trial, the blood flow reductions in internal carotid artery (-26 ± 14%) and vertebral artery (-27 ± 14%) were greater than the decline in middle cerebral artery (-21 ± 15%) and posterior middle cerebral artery velocities (-19 ± 10%), respectively (P≤0.01). Significant reductions in the diameter of both the ICA (~5%) and VA (~7%) contributed to the decline in cerebral perfusion with systemic hypotension, independent of hypocapnia. In summary, our findings indicate that blood flow in the VA, unlike the ICA, is sensitive to changes hypotension and hypocapnia. We show for the first time that the decline in global CBF with hypotension is influenced by arterial constriction in the ICA and VA. Additionally, our findings suggest TCD measures of blood flow velocity may modestly underestimate changes in CBF during hypotension with and without hypocapnia, particularly in the posterior circulation.
[Show abstract][Hide abstract] ABSTRACT: The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO2 would affect cerebral metabolism more than hypoxia. PaO2 and PaCO2 were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial-jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO2-H(+) relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO2 reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.Journal of Cerebral Blood Flow & Metabolism advance online publication, 18 February 2015; doi:10.1038/jcbfm.2015.4.
[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. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sport-related concussion has been referred to as a functional rather than a structural injury with neurometabolic and microstructural alterations reported in several studies. Accordingly, conventional neuroimaging techniques, such as computed tomography (CT) and structural magnetic resonance imaging (MRI), have limited value beyond ruling out structural injury such as a contusion or hemorrhage. This chapter presents a review of three neuroimaging techniques that offer insight into the connectivity and neurometabolic consequences of concussion. A number of studies have now been published using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI)/diffusion-weighted imaging, and transcranial Doppler ultrasound (TCD) with varying findings. The results of these studies will be presented, together with current and possible future application of these techniques within the field of sport-related concussion.
[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: Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion.
A narrative and systematic review of articles published in the English language, from December 1982 to October 2013.
Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included.
Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US.
These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
British Journal of Sports Medicine 12/2014; 49(16). DOI:10.1136/bjsports-2014-093901 · 5.03 Impact Factor
[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; 593(5). DOI:10.1113/jphysiol.2014.284521 · 5.04 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
Frontiers in Physiology 11/2014; 5. DOI:10.3389/fphys.2014.00458 · 3.53 Impact Factor
[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: 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 and sit-to-stand 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 postrecovery 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 interindividual 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 thigh-cuff deflation and sit-to-stand 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.
[Show abstract][Hide abstract] ABSTRACT: Key points:
Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms. Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change. Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and PCO2. We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid-base status correction, indicating that pulmonary pressure, pH and PCO2 are unlikely regulators of IPAVA blood flow.
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 Pa,CO2. AZ decreased pH (-0.08 ± 0.01), [HCO3(-)] (-7.1 ± 0.7 mmol l(-1)) and Pa,CO2 (-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 Pa,CO2.
The Journal of Physiology 11/2014; 593(3). DOI:10.1113/jphysiol.2014.282962 · 5.04 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.