Changes In PETCO2 Research Articles

Cerebral blood flow changes during tilt table testing in healthy volunteers, as assessed by Doppler imaging of the carotid and vertebral arteries

ObjectivesUsing different techniques, reduction of cerebral blood flow (CBF) during orthostatic stress were demonstrated. One study reported flow reduction of the right internal carotid (ICA) and vertebral (VA) artery during orthostatic stress by Doppler imaging, with different effects on the 2 vessels. Global CBF changes, using this technique, have not been reported. Therefore, flow of the ICA, VA and global CBF were measured during head-up tilt testing. Methods33 healthy volunteers underwent tilt testing. At three time points (supine, half way and at the end of the test) Doppler imaging of the ICA and VA was performed, as well as PetCO2 measurements. ResultsGlobal CBF was significantly reduced by 4.5 ± 2.8% halfway the test and by 6.0 ± 3.4% at the end. All 4 artery flows were significantly reduced during the tilt, without differences between them. Despite small changes in PetCO2 there was a significant relation between de CBF decrease and PetCO2 decrease (p < 0.05). ConclusionsOrthostatic stress in HV results in a small but significant reduction of CBF by a homogenous reduction in the four cerebral vessels and is modulated by PetCO2 changes. SignificanceCBF changes can be measured during tilt testing using Doppler VA and ICA imaging.

Quantitative analysis of the effect of end-tidal carbon dioxide on regional cerebral oxygen saturation in patients undergoing carotid endarterectomy under general anaesthesia.

Regional cerebral oxygen saturation (rSO2 ) is currently the most used measure in clinical practice to monitor cerebral ischaemia in patients undergoing carotid endarterectomy (CEA). Although end-tidal carbon dioxide (PET CO2 ) is known as a factor that influences rSO2 , the relationship between PET CO2 and rSO2 has not been quantitatively evaluated in patients with severe arteriosclerosis. This study aimed to evaluate the effect of PET CO2 on rSO2 in patients undergoing CEA under general anaesthesia. The intervention to change PET CO2 was conducted between skin incision and clamping of the carotid artery. The rSO2 values were observed by changing PET CO2 in the range of 25-45mmHg. The PET CO2 -rSO2 relationship was characterized by population analysis using a turnover model. In total, 1651 rSO2 data points from 30 patients were used to determine the pharmacodynamic characteristics. Hypertension (HTN) and systolic blood pressure (SBP) were significant covariates on the slope factor in the stimulatory effect of PET CO2 on rSO2 and fractional turnover rate constant (kout ), respectively. The estimates of the parameters were kout (min-1 ): 3.59 for SBP<90mmHg and 0.491 for SBP ≥90mmHg, slope: 0.00321 for patients with HTN and 0.00664 for patients without HTN. The presence of HTNattenuates the response of rSO2 after a change in PET CO2 . When cerebral blood flow is in a state of decline caused by a decrease in SBP to <90mmHg, the response of rSO2 to PET CO2 is increased. It is advisable to maintain SBP >90mmHg in patients with HTNduring CEA.

Effect of arterial puncture on ventilation

BackgroundClinicians frequently assume that during arterial puncture for measuring arterial blood gases patients hyperventilate from pain and anxiety. This assumption leads clinicians to falsely interpret a PaCO2 and pH near the upper limit of normal as a chronic respiratory acidosis corrected by an acute respiratory alkalosis. ObjectiveDetermine if participants hyperventilate during arterial puncture from pain and anxiety. MethodsWe recruited participants from a pulmonary function laboratory referred for arterial blood gas measurement. We excluded those with heart failure and included those with any respiratory condition (COPD, asthma, sleep apnea). We measured end tidal PCO2 (PETCO2), respiratory rate, and heart rate 15 min before topical anesthesia, during anesthesia, during arterial puncture, and 15 min later. We assessed generalized anxiety before and measured pain during and after arterial puncture. Results24 participants were recruited (age: 54 ± 12 years; men: 54%). PaCO2 was 41 ± 5 mmHg. One had acute respiratory alkalosis. Respiratory rate increased from (19 ± 6 breaths per minute (bpm)) before to a maximum (21 ± 6 bpm) during arterial puncture (p = 0.001). Heart rate was stable throughout. The lowest PETCO2 during the procedure (35 ± 5) was similar to PETCO2 before the procedure (p = 0.1). The change in PETCO2 and respiratory rate did not correlate with pain, anxiety, or lung function. ConclusionRespiratory rate increased slightly during arterial puncture without any change in PETCO2. Hence, acid–base status must be interpreted without the assumption of procedure induced hyperventilation.

The Effect of a Patent Foramen Ovale and Sex on the Hypercapnic Ventilatory Response

A patent foramen ovale (PFO) is a right‐to‐left intracardiac shunt pathway present in approximately 35% of the general healthy population. Individuals with a PFO (PFO+) exhibit higher alveolar to arterial oxygen difference (AaDO2) values at rest than subjects without a PFO (PFO−), indicating that PFO+ subjects have a source of right‐to‐left shunt significant enough to decrease gas exchange efficiency at rest. Additionally, PFO+ subjects have blunted ventilatory acclimatization to hypoxia compared to PFO− subjects. While the presence of a PFO is known to influence hypoxic chemosensitivity, it has yet to be determined if the presence of a PFO has an effect on the hypercapnic ventilatory response (HCVR).Thirty subjects (15 female) matched for height, weight, sex and age participated in this study. Subjects completed two hypercapnic breathing trials in a randomized and balanced order, separated by ≥ 40 minutes of rest between trials. At the start of each trial, subjects began breathing room air until steady‐state values for end‐tidal oxygen and carbon dioxide (PETO2 and PETCO2) were established. PETO2 and PETCO2 were then controlled utilizing a dynamic end‐tidal forcing system (AirForce). During the hyperoxic hypercapnia (HH) trial, PETO2 was clamped at 250 mmHg and PETCO2 was increased in a stepwise fashion to target values of +3 mmHg, +6 mmHg and +9 mmHg of each subject's baseline PETCO2. Each stage consisted of a 90 second steady‐state data collection period after each increase. The procedure for the normoxic hypercapnia (NH) trial was identical to the HH trial except that PETO2 was clamped at the resting baseline value for each subject and PETCO2 increased as above. Hypercapnic ventilatory response (HCVR) was calculated as the change in minute ventilation (VE) divided by the change in PETCO2 (L/min/Torr CO2).PFO+ subjects demonstrated a blunted, significantly lower HCVR than PFO− subjects during both the HH (PFO−: 1.80 L/min/Torr CO2 ± 0.17, PFO+: 1.19 L/min/Torr CO2 ± 0.14, p &lt; 0.05) and NH (PFO−: 1.79 L/min/Torr CO2 ± 0.23, PFO+: 1.24 L/min/Torr CO2 ± 0.26, p &lt; 0.05) trials. These data suggest that PFO+ subjects have a blunted ventilatory response to acute exposure to hypercapnia. Within the subset of female subjects, PFO+ females had a significantly lower HCVR than PFO− females in the HH trial (PFO−: 1.85 L/min/Torr CO2 ± 0.27, PFO+: 1.06 L/min/Torr CO2 ± 0.13, p &lt; 0.05) and NH trial (PFO−: 1.81 L/min/Torr CO2 ± 0.28, PFO+: 1.15 L/min/Torr CO2 ± 0.11, p &lt; 0.05). However, no differences were observed between the male PFO+ and PFO− subjects in the HH (PFO−: 1.77 L/min/Torr CO2 ± 0.37, PFO+: 1.35 L/min/Torr CO2 ± 0.24, p &gt; 0.05) or NH (PFO−: 1.76 L/min/Torr CO2 ± 0.24, PFO+: 1.33 L/min/Torr CO2 ± 0.28, p &gt; 0.05) trials. These results suggest that female PFO+ subjects have a blunted HCVR compared to female PFO− subjects.

A generalized method for controlling end-tidal respiratory gases during nonsteady physiological conditions.

While forcing of end-tidal gases by regulating inspired gas concentrations is a common technique for studying cardiorespiratory physiology, independently controlling end-tidal gases is technically challenging. Feedforward control methods are challenging because end-tidal values vary as a dynamic function of both inspired gases and other nonregulated physiological parameters. Conventional feedback control is limited by delays within the lungs and body tissues and within the end-tidal forcing system itself. Consequently, modern end-tidal forcing studies have generally restricted their analysis to simple time courses of end-tidal gases and to resting steady-state conditions. To overcome these limitations, we have designed and validated a more generalized end-tidal forcing system that removes the need for manual tuning and rule-of-thumb based control heuristics, while allowing for accurate control of gases along spontaneous and complicated time courses and under nonsteady physiological conditions. On average during resting, steady walking, and walking with time varying speed, our system achieved step changes in PetCO2 within 3.0 ± 0.9 (mean ± SD) breaths and PetO2 within 4.4 ± 0.9 breaths, while also maintaining small steady-state errors of 0.1 ± 0.2 mmHg for PetCO2 and 0.3 ± 0.8 mmHg for PetO2 The system also accurately tracked more complicated changes in end-tidal values through a bandwidth of 1/10 the respiratory (sampling) frequency, a practical limit of feedback control systems. The primary mechanism enabling this controller performance is a generic mathematical model of the cardiopulmonary system that captures the breath-by-breath relationship between inspired and end-tidal gas concentrations, with secondary contributions from reduced delays in controlled air delivery.

The Equilibration of Pco 2 in Pigs Is Independent of Lung Injury and Hemodynamics

In mechanical ventilation, normoventilation in terms of PCO2 can be achieved by titration of the respiratory rate and/or tidal volume. Although a linear relationship has been found between changes in respiratory rate and resulting changes in end-tidal cO2 (△PetCO2) as well as between changes in respiratory rate and equilibration time (teq) for mechanically ventilated patients without lung injury, it is unclear whether a similar relationship holds for acute lung injury or altered hemodynamics. We performed a prospective randomized controlled animal study of the change in PetCO2 with changes in respiratory rate in a lung-healthy, lung-injury, lung-healthy + altered hemodynamics, and lung-injury + altered hemodynamics pig model. University research laboratory. Twenty mechanically ventilated pigs. Moderate lung injury was induced by injection of oleic acid in 10 randomly assigned pigs, and after the first round of measurements, cardiac output was increased by approximately 30% by constant administration of noradrenalin in both groups. We systematically increased and decreased changes in respiratory rate according to a set protocol: +2, -4, +6, -8, +10, -12, +14 breaths/min and awaited equilibration of Petco2. We found a linear relationship between changes in respiratory rate and △PetCO2 as well as between changes in respiratory rate and teq. A two-sample t test resulted in no significant differences between the lung injury and healthy control group before or after hemodynamic intervention. Furthermore, exponential extrapolation allowed prediction of the new PetCO2 equilibrium and teq after 5.7 ± 5.6 min. The transition between PetCO2 equilibria after changes in respiratory rate might not be dependent on moderate lung injury or cardiac output but on the metabolic production or capacity of cO2 stores. Linear relationships previously found for lung-healthy patients and early prediction of PetCO2 equilibration could therefore also be used for the titration of respiratory rate on the PetCO2 for a wider range of pathologies by the physician or an automated ventilation system.

Regional differences in the vascular response to CO2 among cerebral, ocular, and mesenteric vessels

BackgroundIt is well-known that cerebral and ocular vessels are highly sensitive to changes in the partial pressure of CO2 (PETCO2). However, it is unclear whether there are regional differences in the magnitude of the vascular response to CO2 (CO2 reactivity) in various vessels of a single individual, and whether there is a relationship in the CO2 reactivity of specific vessels between different individuals. MethodsWe compared the CO2 reactivity of the superior mesenteric artery (SMA), middle cerebral artery (MCA), retinal artery (RA), and retinal and choroidal vessels (RCV) during a 3-min inhalation of CO2-rich air (5%) in 70 subjects. ResultsThe blood flow velocities in the MCA, RA, and RCV significantly increased by 21 ± 2% (mean ± SE), 9 ± 1%, and 7 ± 2%, respectively (P < 0.05) during hypercapnia, whereas that in the SMA did not change significantly (−17 ± 11%). The CO2 reactivity–the relative change in blood flow to a given change in PETCO2–was significantly greater in the MCA (2.2 ± 0.2%/mmHg) than in the RA and RCV (0.9 ± 0.1%/mmHg and 0.8 ± 0.2%/mmHg, respectively). There was a weak correlation in the CO2 reactivity only between RA and RCV (r = 0.43, P < 0.05). ConclusionThese findings indicate that the CO2 reactivity can vary even in cerebral and ocular vessels, although the correlation is weak.

Respiratory Gas Exchange and Early Response to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has become an accepted device therapy for chronic heart failure (HF), however, the response to therapy has been variable with approximately 25∼30% of patients considered non-responders. PURPOSE: To determine if exercise respiratory gas exchange obtained prior to CRT implantation may predict early response to CRT. METHODS: Prior to CRT implantation, patients were assigned to either a mild-moderate group (Mod G, age= 67±10yrs) or a moderate-severe group (Sev G, age=67±10yrs) based on abnormalities in exercise gas exchange. Gas exchange severity was based on a score from the measures of VE/VCO2 slope, resting PETCO2 and a change in PETCO2 from resting to peak. All measurements were performed pre- and 3∼4 mo-post CRT implantation. RESULTS: While the Mod G did not improve gas exchange (p>0.05), the Sev G improved significantly (p0.05), however, the Sev G significantly improved RVSP by 23% (50±14 vs. 42± 12 mmHg, p<0.05). Both groups improved LVEF (p<0.05), New York Heart Association (NYHA, p<0.05) and QOL (quality of life, p<0.05), but no significant differences were observed between groups (p>0.05). No significant changes were observed in brain natriuretic peptide (BNP) in either group post CRT. CONCLUSION: Based on pre CRT implantation cardiopulmonary gas exchange, subjects with the most impaired values appeared to have more improvement post CRT possibly mediated through a decrease in RVSP. Supported by NIH Grant HL98663 and HL71478

Attenuated Cerebral Vasodilatory Capacity in Response to Hypercapnia in Young Obese Individuals

Obese individuals are at a greater risk for the development of a variety of cardio and cerebral vascular diseases including hypertension, atherosclerosis, coronary artery disease and stroke. Furthermore, obesity is also associated with cognitive impairment and is a risk factor for dementia and Alzheimer's disease. The exact mechanisms of this elevated risk are not fully characterized; however, impaired microvascular function is believed to be a contributor. This study tested the hypothesis that the cerebral vasodilatory capacity in response to hypercapnia is reduced in obese individuals relative to age and sex matched lean counterparts. Cerebral blood velocity (CBFV) was measured using transcranial Doppler before and during rebreathing‐induced hypercapnia in obese (Obese, n=14) and lean (Lean, n=14) subjects. Cerebral vascular conductance (CVCI) was calculated as CBFV / mean arterial pressure (MAP), and a four parameter logistic regression was applied for sigmoidal curve fitting of the relationship between % change in CVCI and end‐tidal CO2 tension (PETCO2). The magnitude of hypercapnia (Δ PETCO2) during rebreathing was similar between groups (Obese 14 ± 3 mmHg vs. Lean: 15 ± 2 mmHg; P = 0.13). The maximum increase in CVCI (Obese: 155 ± 17% vs. Lean: 176 ± 23%; P &lt; 0.05) and the total range of change in CVCI (Obese: 50 ± 15% vs. Lean: 75 ± 22%; P &lt; 0.01) during rebreathing were reduced in the obese relative to the lean individuals. These data indicate that cerebral vasodilatory capacity in response to changes in PETCO2 during hypercapnia is attenuated in obese individuals compared with lean individuals.This study was supported by institutional start‐up funds awarded to R. Matthew Brothers.

The influence of inner and heard speech in arts speech therapy on brain oxygenation and hemodynamics

Purpose: Artistic speech therapy is applied in anthroposophically extended medicine to treat several diseases. The aim is to understand the physiology by investigating the effect of inner and heard speech on brain hemodynamics and oxygenation and analyzing whether these changes were affected by changes in arterial carbon dioxide pressure. Methods: In 29 healthy adult volunteers changes in cerebral absolute oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO2) were measured by functional near-infrared spectroscopy (fNIRS). End-tidal CO2 (PETCO2) was assessed by capnography. Each subject performed six tasks: inner speech, heard speech from a person and heard speech from a record with each two different recitation texts: hexameter and alliteration according to a randomized crossover design. Results: Significant changes during tasks: A decrease in StO2, [O2Hb], [tHb] and PETCO2 (only for inner speech); an increase in [HHb]. There was a significant difference between hexameter and alliteration. Particularly, changes in [tHb] at the left prefrontal cortex during tasks and after them were statistically different. Furthermore we found significant relations between changes in [O2Hb], [HHb], [tHb] or StO2 and the participants’ age, the baseline PETCO2, or certain speech tasks. Conclusion: During the inner speech, hyperventilation led to a lower PETCO2 (hypocapnia). During heard speech no significant changes in PETCO2 occurred. But decreases in StO2, [O2Hb], [tHb] suggest hypocapnia also here. Hexameter and alliteration led to different changes in [tHb]. Consequently, our parameters are affected by an interplay of both PETCO2 response and task dependent functional brain activity.

Cardiovascular responses to water immersion in humans: impact on cerebral perfusion

Episodic increases in cerebrovascular perfusion and shear stress may have beneficial impacts on endothelial function that improve brain health. We hypothesized that water immersion to the level of the right atrium in humans would increase cerebral perfusion. We continuously measured, in 9 young (means ± SD, 24.6 ± 2.0 yr) healthy men, systemic hemodynamic variables along with blood flows in the common carotid and middle and posterior cerebral arteries during controlled filling and emptying of a water tank to the level of the right atrium. Mean arterial pressure (80 ± 9 vs. 91 ± 12 mmHg, P < 0.05), cardiac output (4.8 ± 0.7 vs. 5.1 ± 0.6 l/min, P < 0.05) and end-tidal carbon dioxide (PetCO2, 39.5 ± 2.0 vs. 44.4 ± 3.5 mmHg, P < 0.05) increased with water immersion, along with middle (59 ± 6 vs. 64 ± 6 cm/s, P < 0.05) and posterior cerebral artery blood flow velocities (41 ± 9 vs. 44 ± 10 cm/s, P < 0.05). These changes were reversed when the tank was emptied. Water immersion is associated with hemodynamic and PetCO2 changes, which increase cerebral blood velocities in humans. This study provides an evidence base for future studies to examine the potential additive effect of exercise in water on improving cerebrovascular health.

Dynamic Cerebral Autoregulation Is Acutely Impaired during Maximal Apnoea in Trained Divers

AimsTo examine whether dynamic cerebral autoregulation is acutely impaired during maximal voluntary apnoea in trained divers.MethodsMean arterial pressure (MAP), cerebral blood flow-velocity (CBFV) and end-tidal partial pressures of O2 and CO2 (PETO2 and PETCO2) were measured in eleven trained, male apnoea divers (28±2 yr; 182±2 cm, 76±7 kg) during maximal “dry” breath holding. Dynamic cerebral autoregulation was assessed by determining the strength of phase synchronisation between MAP and CBFV during maximal apnoea.ResultsThe strength of phase synchronisation between MAP and CBFV increased from rest until the end of maximal voluntary apnoea (P<0.05), suggesting that dynamic cerebral autoregulation had weakened by the apnoea breakpoint. The magnitude of impairment in dynamic cerebral autoregulation was strongly, and positively related to the rise in PETCO2 observed during maximal breath holding (R 2 = 0.67, P<0.05). Interestingly, the impairment in dynamic cerebral autoregulation was not related to the fall in PETO2 induced by apnoea (R 2 = 0.01, P = 0.75).ConclusionsThis study is the first to report that dynamic cerebral autoregulation is acutely impaired in trained divers performing maximal voluntary apnoea. Furthermore, our data suggest that the impaired autoregulatory response is related to the change in PETCO2, but not PETO2, during maximal apnoea in trained divers.

Changes of end-tidal carbon dioxide during cardiopulmonary resuscitation from ventricular fibrillation versus asphyxial cardiac arrest.

Partial pressure of end-tidal carbon dioxide (PETCO2) has been used to monitor the effectiveness of precordial compression (PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation (CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fibrillation (VF) versus asphyxial cardiac arrest. Sixty-two male Sprague-Dawley (SD) rats were randomly divided into an asphyxial group (n=32) and a VF group (n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest. The initial values of PETCO2 immediately after PC in the VF group were significantly lower than those in the asphyxial group (12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation (ROSC), compared with those in rats without ROSC (16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were significantly higher than those in rats without ROSC (20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic (ROC) curves of PETCO2 showed significant sensitivity and specificity for predicting ROSC in VF versus asphyxial cardiac arrest. The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.

Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising

Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved.Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1Hz in 16 healthy subjects. The MABP–CBFV phase difference and gain were determined at 0.1Hz and in the low frequency (LF) range (0.06–0.14Hz). In addition the autoregulation index (ARI) was calculated.The LR maneuver increased the power of MABP fluctuations at 0.1Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP–CBFV phase difference at 0.1Hz Variability was not reduced by LR for any of the dCA parameters.The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant.

The dynamics of carbon dioxide equilibration after alterations in the respiratory rate

Manual or automated control of mechanical ventilation can be realized as an open or closed-loop system for which the regulation of the ventilation parameters ideally is tuned to the dynamics and equilibration time of the biological system. We investigated the dynamic, transient state and equilibration time (teq) of the CO2 partial pressure (PCO2) after changes in the respiratory rate (ΔRR). In 17 anaesthetized patients without known history of lung disease, respiratory rate was alternately increased and decreased and end-tidal CO2 partial pressures (PetCO2) were measured. Linear relations were found between ΔRR and PetCO2 changes (ΔPetCO2 = 0.3 − 1.1 · ΔRR) and between ΔRR and teq for increasing and decreasing RR (teq(hypervent) = 0.5 · |ΔRR|, teq(hypovent) = 0.7 · |ΔRR|). Extrapolation of the transition between two PCO2 steady-states allowed for the prediction of the new PCO2 steady-state as early as 0.5 · teq with an error <4 mmHg. At bedside or in automated ventilation systems, the linear dependencies between ΔRR and ΔPCO2 and between ΔRR and teq as well as early steady-state prediction of PCO2 could be used as a guidance towards a timing and step size regulation of RR that is well adapted to the biological system.

Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO2 Inhalation

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO2 (PETCO2). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO2 for prospective targeting of PETCO2, (2) administration of a fixed concentration of CO2 leading to subject-dependent changes in PETCO2, (3) a breath-hold (BH) paradigm with physiologic modeling of CO2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in PETCO2, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100 g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO2 dose-response curve, avoiding hypocapnic conditions.

Cerebrovascular reactivity and implications for understanding the pathophysiology of multiple sclerosis

Multiple sclerosis (MS) is a severe neurological disease commonly diagnosed in young adults. Recent controversial publications attribute the inflammation, sclerosis, and degenerative lesions to venous insufficiency. We recently found characteristic reductions in cerebrovascular reactivity (CVR) in the presence of venous congestion caused by other neurological disorders. We therefore hypothesize that CVR may also be reduced in patients with MS. A computer‐controlled gas blender (RespirAct™, TRI, Canada) was used to precisely target normoxic PETCO2 changes between 40 to 50 mmHg in 7 MS subjects with varying type and severity. BOLD MRI was performed simultaneously as an indirect measure of changes in cerebral blood flow. CVR, defined on a voxel‐wise basis as %ΔBOLD signal/ΔPETCO2, was color coded and superimposed on anatomical scans to form CVR maps. Each CVR map was compared voxel‐by‐voxel with a CVR atlas generated from 37 healthy subjects. Contrary to our hypothesis, CVR in MS subjects was greater than the healthy cohort. The degree of hyper‐reactivity correlated with the severity of MS. Regions of increased CVR may reflect the confounding dependency of BOLD MRI on cerebral blood volume which could be increased due to insufficient venous drainage. However, it may actually reflect an increased flow response to hypercapnia which overwhelms the altered venous draining system leading to venous congestion.

Cerebral hypoperfusion modifies the respiratory chemoreflex during orthostatic stress

The respiratory chemoreflex is known to be modified during orthostatic stress although the underlying mechanisms remain to be established. To determine the potential role of cerebral hypoperfusion, we examined the relationship between changes in MCA Vmean (middle cerebral artery mean blood velocity) and V̇E (pulmonary minute ventilation) from supine control to LBNP (lower body negative pressure; −45mmHg) at different CO2 levels (0, 3.5 and 5% CO2). The regression line of the linear relationship between V̇E and PETCO2 (end-tidal CO2) shifted leftwards during orthostatic stress without any change in sensitivity (1.36±0.27 l/min per mmHg at supine to 1.06±0.21 l/min per mmHg during LBNP; P=0.087). In contrast, the relationship between MCA Vmean and PETCO2 was not shifted by LBNP-induced changes in PETCO2. However, changes in V̇E from rest to LBNP were more related to changes in MCA Vmean than changes in PETCO2. These findings demonstrate for the first time that postural reductions in CBF (cerebral blood flow) modified the central respiratory chemoreflex by moving its operating point. An orthostatically induced decrease in CBF probably attenuated the ‘washout’ of CO2 from the brain causing hyperpnoea following activation of the central chemoreflex.

Cerebral hypoperfusion modifies the respiratory chemoreflex during orthostatic stress

The respiratory chemoreflex is known to be modified during orthostatic stress although the underlying mechanisms remain to be established. To determine the potential role of cerebral hypoperfusion, we examined the relationship between changes in MCA V(mean) (middle cerebral artery mean blood velocity) and ˙VE (pulmonary minute ventilation) from supine control to LBNP (lower body negative pressure; −45mmHg) at different CO(2) levels (0, 3.5 and 5% CO(2)). The regression line of the linear relationship between ˙V(E) and PETCO(2) (end-tidal CO(2)) shifted leftwards during orthostatic stress without any change in sensitivity (1.36+− 0.27 l/min per mmHg at supine to 1.06+− 0.21 l/min per mmHg during LBNP; P=0.087). In contrast, the relationship between MCA V(mean) and PETCO(2) was not shifted by LBNP-induced changes in PETCO2. However, changes in ˙V(E) from rest to LBNP were more related to changes in MCA V(mean) than changes in PETCO(2). These findings demonstrate for the first time that postural reductions in CBF (cerebral blood flow) modified the central respiratory chemoreflex by moving its operating point. An orthostatically induced decrease in CBF probably attenuated the ‘washout’ of CO(2) from the brain causing hyperpnoea following activation of the central chemoreflex.

Changes in cerebral blood flow and vasoreactivity to CO2 measured by arterial spin labeling after 6days at 4350m

Changes in cerebral perfusion and CO2 cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO2 by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO2 CVR. End-tidal CO2 (PetCO2), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO2 CVR. CO2 CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO2. PetCO2 was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5%). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1% and 20.5±20.3%, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4350m (-12.3±54.5% in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8% in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO2 CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.