Differential regional cerebrovascular reactivity to end-tidal gas combinations commonly seen during anaesthesia: A blood oxygenation level-dependent MRI observational study in awake adult subjects.

BACKGROUND: Regional cerebrovascular reactivity (rCVR) is highly variable in the human brain as measured by blood oxygenation level-dependent (BOLD) MRI to changes in both end-tidal CO 2 and O 2 . OBJECTIVES: We examined awake participants under carefully controlled end-tidal gas concentrations to assess how regional CVR changes may present with end-tidal gas changes seen commonly with anaesthesia. DESIGN: Observational study. SETTING: Tertiary care centre, Winnipeg, Canada. The imaging for the study occurred in 2019. SUBJECTS: Twelve healthy adult subjects. INTERVENTIONS: Cerebral BOLD response was studied under two end-tidal gas paradigms. First end-tidal oxygen (ETO 2 ) maintained stable whereas ETCO 2 increased incrementally from hypocapnia to hypercapnia (CO 2 ramp); second ETCO 2 maintained stable whereas ETO 2 increased from normoxia to hyperoxia (O 2 ramp). BOLD images were modeled with end-tidal gas sequences split into two equal segments to examine regional CVR. MAIN OUTCOME MEASURES: The voxel distribution comparing hypocapnia to mild hypercapnia and mild hyperoxia (mean F I O 2  = 0.3) to marked hyperoxia (mean F I O 2  = 0.7) were compared in a paired fashion ( P  < 0.005 to reach threshold for voxel display). Additionally, type analysis was conducted on CO 2 ramp data. This stratifies the BOLD response to the CO 2 ramp into four categories of CVR slope based on segmentation (type A; +/+slope: normal response, type B +/-, type C -/-: intracranial steal, type D -/+.) Types B to D represent altered responses to the CO 2 stimulus. RESULTS: Differential regional responsiveness was seen for both end-tidal gases. Hypocapnic regional CVR was more marked than hypercapnic CVR in 0.3% of voxels examined ( P  < 0.005, paired comparison); the converse occurred in 2.3% of voxels. For O 2 , mild hyperoxia had more marked CVR in 0.2% of voxels compared with greater hyperoxia; the converse occurred in 0.5% of voxels. All subjects had altered regional CO 2 response based on Type Analysis ranging from 4 ±â€Š2 to 7 ±â€Š3% of voxels. CONCLUSION: In awake subjects, regional differences and abnormalities in CVR were observed with changes in end-tidal gases common during the conduct of anaesthesia. On the basis of these findings, consideration could be given to minimising regional CVR fluctuations in patients-at-risk of neurological complications by tighter control of end-tidal gases near the individual's resting values.

Cerebrovascular reactivity deficits in cognitively unimpaired older adults: vasodilatory versus vasoconstrictive responses.

Cerebrovascular reactivity (CVR) deficits may index vulnerability to vascular brain injury and cognitive impairment, but findings on age-related changes in CVR have been mixed, and no studies to date have directly compared age-related changes in CVR to hypercapnia versus hypocapnia. The present study compared CVR in 31 cognitively unimpaired older adults (ages 55-87) and 30 healthy younger adults (ages 18-28). Breath control tasks induced CVR to hypocapnia (0.1 Hz paced breathing) and hypercapnia (15s breath holds) during pseudo-continuous arterial spin labeling MRI. Relative to younger adults, cognitively unimpaired older adults displayed lower levels of global CVR under both hypocapnia and hypercapnia. In region-of-interest analyses, older adults exhibited attenuated CVR to hypocapnia in select frontal and temporal regions, and lower CVR to hypercapnia in all cortical, limbic, and subcortical regions examined, relative to younger adults. Results indicate age-related deficits in CVR are detectible even in cognitively unimpaired older adults and are disproportionately related to vasodilatory (hypercapnia) responses relative to vasoconstrictive (hypocapnia) responses. Findings may offer means for early detection of cerebrovascular dysfunction.

Hypocapnia Induced by Hyperventilation with Indocyanine Green Kinetics Detects the Effect of Staged Carotid Angioplasty to Avoid Hyperperfusion in Patients with Impaired Cerebral Hemodynamic Reserve.

Cerebral hyperperfusion syndrome (CHS) is a serious complication following carotid artery stenting (CAS). Staged angioplasty (AP) could potentially prevent CHS and hyperperfusion phenomenon (HPP) after revascularization. However, methods for measuring the effects of staged AP on cerebral hemodynamic reserve have not been established. Here, we evaluated whether indocyanine green kinetics and near-infrared spectroscopy (ICG-NIRS) with hypocapnia induced by hyperventilation can detect the effects of staged AP on hemodynamic reserve to prevent CHS after CAS. Participants comprised 44 patients at high risk of CHS, whose ipsilateral cerebrovascular reactivity (CVR) was impaired on preoperative single photon emission computed tomography (SPECT). Patients were divided into a staged AP group (n=13) and a regular CAS group (n=31). In the staged AP group, stenting was performed 3 weeks after staged AP. In the regular CAS group, 16 cases (52%) showed HPP, and five (16%) presented with CHS after CAS, while no HPP or CHS occurred in the staged AP group (p=0.001). Changes in blood flow index (BFI) and time to peak (TTP) ratio during hypocapnia calculated from ICG-NIRS indicated a significant linear relationship with preprocedural CVR on SPECT (r=-0.710, 0.632, respectively; p<0.0001 each). BFI and TTP ratios during hypocapnia were significantly improved after staged AP (p<0.001 each). Furthermore, significant linear correlations were observed between BFI and TTP ratio during hypocapnia and postoperative asymmetry index AI (r=0.405, -0.475, respectively; p<0.01 each). Hypocapnia induced by hyperventilation under ICG-NIRS appears useful for detecting the effects of staged AP on hemodynamic reserve in patients at high risk of CHS.

Dynamic optic nerve sheath diameter changes upon moderate hyperventilation in patients with traumatic brain injury.

BACKGROUND: Sonographic assessment of optical nerve sheath diameter (ONSD) has the potential for non-invasive monitoring of intracranial pressure (ICP). Hyperventilation (HV) -induced hypocapnia is used in the management of patients with traumatic brain injury (TBI) to reduce ICP. This study investigates, whether sonography is a reliable tool to detect dynamic changes in ONSD. METHODS: This prospective single center trial included patients with TBI and neuromonitoring within 36 h after injury. Data collection and ONSD measurements were performed at baseline and during moderate HV for 50 min. Patients not suffering from TBI were recruited as control group. RESULTS: Ten patients with TBI (70% males, mean age 35 ± 14 years) with a median of first GCS of 5.9 and ten control patients (40% males, mean age 45 ± 16 years) without presumed intracranial hypertension were included. During HV, ICP decreased significantly (p < .0001) in the TBI group. An ONSD response was found for HV (p = .05). CONCLUSION: We observed a dynamic decrease of ONSD during moderate HV. This suggests a potential use of serial ONSD measurements when applying HV in cases of suspected intracranial hypertension.

Cerebral vasomotor reactivity during hypo- and hypercapnia across the adult lifespan.

Age is the strongest risk factor for cerebrovascular disease; however, age-related changes in cerebrovascular function are still not well understood. The objective of this study was to measure cerebral vasomotor reactivity (CVMR) during hypo- and hypercapnia across the adult lifespan. One hundred fifty-three healthy participants (21-80 years) underwent measurements of cerebral blood flow velocity (CBFV) via transcranial Doppler, mean arterial pressure (MAP) via plethysmograph, and end-tidal CO2 (EtCO2) via capnography during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia). Cerebrovascular conductance (CVCi) and resistance (CVRi) indices were calculated from the ratios of CBFV and MAP. CVMRs were assessed by the slopes of CBFV and CVCi in response to changes in EtCO2. The baseline CBFV and CVCi decreased and CVRi increased with age. Advanced age was associated with progressive declines in CVMR during hypocapnia indicating reduced cerebral vasoconstriction, but increases in CVMR during hypercapnia indicating increased vasodilation. A negative correlation between hypo- and hypercapnic CVMRs was observed across all subjects (CBFV%/ EtCO2: r = -0.419, CVCi%/ EtCO2: r = -0.442, P < 0.0001). Collectively, these findings suggest that aging is associated with decreases in CBFV, increases in cerebrovascular resistance, reduced vasoconstriction during hypocapnia, but increased vasodilatory responsiveness during hypercapnia.

Estimation of pulsatile cerebral arterial blood volume based on transcranial doppler signals.

OBJECTIVE: Mathematical modeling of cerebral hemodynamics by descriptive equations can estimate the underlying pulsatile component of cerebral arterial blood volume (CaBV). This way, clinical monitoring of changes in cerebral compartmental compliances becomes possible. Our aim is to validate the most adequate method of CaBV estimation in neurocritical care. APPROACH: We retrospectively reviewed patients with severe traumatic brain injury (TBI) [admitted from 1992-2012] and continuous transcranial Doppler (TCD) monitoring of cerebral blood flow velocity (FV) displaying either plateau waves of intracranial pressure (ICP), episodes of controlled, mild hypocapnia, or vasopressor-induced increases in arterial blood pressure (ABP). Each cohort was analyzed with continuous flow forward (CFF, pulsatile blood inflow and steady blood outflow) or pulsatile flow forward (PFF, both blood inflow and outflow are pulsatile) modeling approaches for estimating the pulse component of CaBV. Spectral pulsatility index (sPI, the first harmonic of the FV pulse/mean FV) can be estimated using the compliance of the vascular bed (Ca) and the cerebrovascular resistance (CVR - here, Ra). We compared three possible methods of assessing Ca (C1: the CFF model, C2 and C3: the PFF models based on ABP or cerebral perfusion pressure (CPP) pulsations, respectively) and combined them with three possible methods of assessing Ra (Ra1= ABP/FV, Ra2= the resistance area product, and Ra3= CPP/FV). Linear regression techniques were applied to describe the strength of each CaBV estimator (a combination of Ca and Ra) against sPI. MAIN RESULTS: The combination of C1 and Ra3 (PI_C1Ra3) was the superior descriptor of CaBV as approximated by sPI for both the plateau waves and the hypocapnia cohorts (r = 0.915 and r = 0.955, respectively). The combination of C1 and Ra1 (PI_C1Ra1) was nearly as robust in the vasopressors cohort (r = 0.938 and r = 0.931, respectively). SIGNIFICANCE: TCD-based estimation of CaBV pulsations seems to be feasible when employing the CFF modeling approach.

Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease.

The present study examined whether preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease. Among 65 adult patients with ischemic moyamoya disease, 19 had misery perfusion in the precentral region on preoperative 15O positron emission tomography and underwent arterial bypass surgery for that region. Brain technetium-99 m-labeled ethyl cysteinate dimer single-photon emission computed tomography (SPECT) was preoperatively performed with and without hyperventilation challenge and relative cerebrovascular contractile reactivity to hypocapnia (RCVCRhypocap) (%/mmHg) was calculated in the precentral region. Development of cerebral hyperperfusion syndrome was determined using perioperative changes of symptoms and brain N-isopropyl-p-[123I]-iodoamphetamine SPECT performed after surgery. RCVCRhypocap was significantly lower in the 6 patients with cerebral hyperperfusion syndrome (-2.85 ± 1.10%/mmHg) than in the 13 patients without cerebral hyperperfusion syndrome (0.18 ± 1.97%/mmHg; p = 0.0050). Multivariate analysis demonstrated low RCVCRhypocap as an independent predictor of cerebral hyperperfusion syndrome (95% confidence interval, 0.04-0.96; p = 0.0433). Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease.

Effects of acute controlled changes in end-tidal carbon dioxide on the diameter of the optic nerve sheath: a transorbital ultrasonographic study in healthy volunteers.

Transorbital ultrasonographic measurement of the diameter of the optic nerve sheath is a non-invasive, bed-side examination for detecting raised intracranial pressure. However, the ability of the optic nerve sheath diameter to predict acute changes in intracranial pressures remains unknown. The aim of this study was to examine the dynamic changes of the optic nerve sheath diameter in response to mild fluctuations in cerebral blood volume induced by changes in end-tidal carbon dioxide. We studied 11 healthy volunteers. End-tidal carbon dioxide was controlled by a model-based prospective end-tidal targeting system (RespirAct™). The volunteers' end-tidal carbon dioxide was targeted and maintained for 10 min each at normocapnia (baseline); hypercapnia (6.5 kPa); normocapnia (baseline 1); hypocapnia (3.9 kPa) and on return to normocapnia (baseline 2). A single investigator repeatedly measured the optic nerve sheath diameter for 10 min at each level of carbon dioxide. With hypercapnia, there was a significant increase in optic nerve sheath diameter, with a mean (SD) increase from baseline 4.2 (0.7) mm to 4.8 (0.8) mm; p < 0.001. On return to normocapnia, the optic nerve sheath diameter rapidly reverted back to baseline values. This study confirms dynamic changes in the optic nerve sheath diameter with corresponding changes in carbon dioxide, and their reversibly with normocapnia.

Heterogeneous patterns of vasoreactivity in the middle cerebral and internal carotid arteries.

This study compared changes in cross-sectional area (CSA) and flow (Q) between the middle cerebral artery (MCA) and the internal carotid artery (ICA) at baseline and during 5 min of hypercapnia (HC; 6% CO2) and hypocapnia (HO; hyperventilation) and quantified how these changes contribute to estimates of cerebrovascular reactivity (CVR). Measures of MCA CSA were made using 3T magnetic resonance imaging. On a separate day, MCA flow velocity was measured with transcranial Doppler ultrasound and ICA diameters and flow velocity were measured with duplex ultrasound. Fourteen subjects (23 ± 3 yr, 7 females) participated, providing data for 11 subjects during HC and 9 subjects during HO. An increase in MCA CSA (P < 0.05) was observed within the first minute of HC. During HO, the decrease in MCA CSA (P < 0.05) was delayed until minute 4. No changes were observed in ICA CSA during HC or HO. The relative changes in QICA and QMCA were similar during HC and HO. Therefore, the MCA, but not ICA, dilates and constricts during 5 min of HC and HO, respectively. The consequent impact on QMCA significantly affects estimates of CVR, and reactivity cannot be attributed solely to changes in smaller arterioles.

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI.

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.

Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia.

To establish the accuracy of transcranial Doppler ultrasound (TCD) measures of middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) as a surrogate of cerebral blood flow (CBF) during hypercapnia (HC) and hypocapnia (HO), we examined whether the cross-sectional area (CSA) of the MCA changed during HC or HO and whether TCD-based estimates of CBFV were equivalent to estimates from phase contrast (PC) magnetic resonance imaging. MCA CSA was measured from 3T magnetic resonance images during baseline, HO (hyperventilation at 30 breaths/min), and HC (6% carbon dioxide). PC and TCD measures of CBFV were measured during these protocols on separate days. CSA and TCD CBFV were used to calculate CBF. During HC, CSA increased from 5.6 ± 0.8 to 6.5 ± 1.0 mm(2) (P < 0.001, n = 13), while end-tidal carbon dioxide partial pressure (PETCO2) increased from 37 ± 3 to 46 ± 5 Torr (P < 0.001). During HO, CSA decreased from 5.8 ± 0.9 to 5.3 ± 0.9 mm(2) (P < 0.001, n = 15), while PetCO2 decreased from 36 ± 4 to 23 ± 3 Torr (P < 0.001). CBFVs during baseline, HO, and HC were compared between PC and TCD, and the intraclass correlation coefficient was 0.83 (P < 0.001). The relative increase from baseline was 18 ± 8% greater (P < 0.001) for CBF than TCD CBFV during HC, and the relative decrease of CBF during HO was 7 ± 4% greater than the change in TCD CBFV (P < 0.001). These findings challenge the assumption that the CSA of the MCA does not change over modest changes in PETCO2.

Cerebral blood flow and transcranial doppler sonography measurements of CO2-reactivity in acute traumatic brain injured patients.

BACKGROUND: Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI. METHOD: CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia. MAIN FINDING AND CONCLUSION: Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

A computerized decision support system to predict the variations in the cerebral blood flow of mechanically ventilated infants.

A computerized decision support system is described to predict the changes in the cerebral blood flow (CBF) of mechanically ventilated infants in response to different ventilatory settings. A CBF controller was developed and combined with a mathematical model of the infant's respiratory system to simulate the effects of ventilatory settings on the infant's CBF. The performance of the system was examined under various ventilatory treatments and the results were compared with available experimental data. The comparisons showed good agreement between the simulation results and experimental data for preterm infants. These included the results obtained under conditions of hypoventilation, hyperventilation, hypoxia, and hyperoxia. The presented decision support system has the potential to be used as an aide to the intensivist in choosing appropriate ventilation treatments for infants to prevent the untoward consequences of hazardous changes in CBF in mechanically ventilated infants such as hypoxic-ischemic brain injuries.

Cerebral vasomotor reactivity during hypo- and hypercapnia in sedentary elderly and Masters athletes.

Physical activity may influence cerebrovascular function. The objective of this study was to determine the impact of life-long aerobic exercise training on cerebral vasomotor reactivity (CVMR) to changes in end-tidal CO2 (EtCO2) in older adults. Eleven sedentary young (SY, 27±5 years), 10 sedentary elderly (SE, 72±4 years), and 11 Masters athletes (MA, 72±6 years) underwent the measurements of cerebral blood flow velocity (CBFV), arterial blood pressure, and EtCO2 during hypocapnic hyperventilation and hypercapnic rebreathing. Baseline CBFV was lower in SE and MA than in SY while no difference was observed between SE and MA. During hypocapnia, CVMR was lower in SE and MA compared with SY (1.87±0.42 and 1.47±0.21 vs. 2.18±0.28 CBFV%/mm Hg, P<0.05) while being lowest in MA among all groups (P<0.05). In response to hypercapnia, SE and MA exhibited greater CVMR than SY (6.00±0.94 and 6.67±1.09 vs. 3.70±1.08 CBFV1%/mm Hg, P<0.05) while no difference was observed between SE and MA. A negative linear correlation between hypo- and hypercapnic CVMR (R(2)=0.37, P<0.001) was observed across all groups. Advanced age was associated with lower resting CBFV and lower hypocapnic but greater hypercapnic CVMR. However, life-long aerobic exercise training appears to have minimal effects on these age-related differences in cerebral hemodynamics.

Regional brain blood flow in man during acute changes in arterial blood gases.

Despite the importance of blood flow on brainstem control of respiratory and autonomic function, little is known about regional cerebral blood flow (CBF) during changes in arterial blood gases.We quantified: (1) anterior and posterior CBF and reactivity through a wide range of steady-state changes in the partial pressures of CO2 (PaCO2) and O2 (PaO2) in arterial blood, and (2) determined if the internal carotid artery (ICA) and vertebral artery (VA) change diameter through the same range.We used near-concurrent vascular ultrasound measures of flow through the ICA and VA, and blood velocity in their downstream arteries (the middle (MCA) and posterior (PCA) cerebral arteries). Part A (n =16) examined iso-oxic changes in PaCO2, consisting of three hypocapnic stages (PaCO2 =∼15, ∼20 and ∼30 mmHg) and four hypercapnic stages (PaCO2 =∼50, ∼55, ∼60 and ∼65 mmHg). In Part B (n =10), during isocapnia, PaO2 was decreased to ∼60, ∼44, and ∼35 mmHg and increased to ∼320 mmHg and ∼430 mmHg. Stages lasted ∼15 min. Intra-arterial pressure was measured continuously; arterial blood gases were sampled at the end of each stage. There were three principal findings. (1) Regional reactivity: the VA reactivity to hypocapnia was larger than the ICA, MCA and PCA; hypercapnic reactivity was similar.With profound hypoxia (35 mmHg) the relative increase in VA flow was 50% greater than the other vessels. (2) Neck vessel diameters: changes in diameter (∼25%) of the ICA was positively related to changes in PaCO2 (R2, 0.63±0.26; P<0.05); VA diameter was unaltered in response to changed PaCO2 but yielded a diameter increase of +9% with severe hypoxia. (3) Intra- vs. extra-cerebral measures: MCA and PCA blood velocities yielded smaller reactivities and estimates of flow than VA and ICA flow. The findings respectively indicate: (1) disparate blood flow regulation to the brainstem and cortex; (2) cerebrovascular resistance is not solely modulated at the level of the arteriolar pial vessels; and (3) transcranial Doppler ultrasound may underestimate measurements of CBF during extreme hypoxia and/or hypercapnia.

How does moderate hypocapnia affect cerebral autoregulation in response to changes in perfusion pressure in TBI patients?

In traumatic brain injury, the hypocapnic effects on blood pressure autoregulation may vary from beneficial to detrimental. The consequences of moderate hypocapnia (HC) on the autoregulation of cerebral perfusion pressure (CPP) have not been monitored so far.Thirty head injured patients requiring sedation and mechanical ventilation were studied during normocapnia (5.1 ± 0.4 kPa) and moderate HC (4.4 ± 3.0 kPa). Transcranial Doppler flow velocity (Fv) of the middle cerebral arteries (MCA), invasive arterial blood pressure, and intracranial pressure were monitored. CPP was calculated. The responsiveness of Fv to slow oscillations in CPP was assessed by means of the moving correlation coefficient, the Mx autoregulatory index. Hypocapnic effects on Mx were increasing with its deviation from normal baseline (left MCA: R (2) = 0.67; right MCA: R (2) = 0.51; p < 0.05). Mx indicating normal autoregulation (left: -0.23 ± 0.23; right: -0.21 ± 0.24) was not significantly changed by moderate HC. Impaired Mx autoregulation, however, (left: 0.37 ± 0.13; right: 0.33 ± 0.26) was improved (left: 0.12 ± 0.25; right: -0.0003 ± 0.19; p < 0.01) during moderate HC. Mx was adjusted to normal despite no significant change in CPP levels. Our study showed that short-term moderate HC may optimize the autoregulatory response to spontaneous CPP fluctuations with only a small CPP increase. Patients with impaired autoregulation seemed to benefit the most.

Transcranial Doppler pulsatility index: what it is and what it isn't.

BACKGROUND: Transcranial Doppler (TCD) pulsatility index (PI) has traditionally been interpreted as a descriptor of distal cerebrovascular resistance (CVR). We sought to evaluate the relationship between PI and CVR in situations, where CVR increases (mild hypocapnia) and decreases (plateau waves of intracranial pressure-ICP). METHODS: Recordings from patients with head-injury undergoing monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), and TCD assessed cerebral blood flow velocities (FV) were analyzed. The Gosling pulsatility index (PI) was compared between baseline and ICP plateau waves (n = 20 patients) or short term (30-60 min) hypocapnia (n = 31). In addition, a modeling study was conducted with the "spectral" PI (calculated using fundamental harmonic of FV) resulting in a theoretical formula expressing the dependence of PI on balance of cerebrovascular impedances. RESULTS: PI increased significantly (p < 0.001) while CVR decreased (p < 0.001) during plateau waves. During hypocapnia PI and CVR increased (p < 0.001). The modeling formula explained more than 65% of the variability of Gosling PI and 90% of the variability of the "spectral" PI (R = 0.81 and R = 0.95, respectively). CONCLUSION: TCD pulsatility index can be easily and quickly assessed but is usually misinterpreted as a descriptor of CVR. The mathematical model presents a complex relationship between PI and multiple haemodynamic variables.

Aging blunts hyperventilation-induced hypocapnia and reduction in cerebral blood flow velocity during maximal exercise.

Cerebral blood flow (CBF) increases from rest to ∼60% of peak oxygen uptake (VO(2peak)) and thereafter decreases towards baseline due to hyperventilation-induced hypocapnia and subsequent cerebral vasoconstriction. It is unknown what happens to CBF in older adults (OA), who experience a decline in CBF at rest coupled with a blunted ventilatory response during VO(2peak). In 14 OA (71 ± 10 year) and 21 young controls (YA; 23 ± 4 years), we hypothesized that OA would experience less hyperventilation-induced cerebral vasoconstriction and therefore an attenuated reduction in CBF at VO(2peak). Incremental exercise was performed on a cycle ergometer, whilst bilateral middle cerebral artery blood flow velocity (MCA V (mean); transcranial Doppler ultrasound), heart rate (HR; ECG) and end-tidal PCO(2) (P(ET)CO(2)) were monitored continuously. Blood pressure (BP) was monitored intermittently. From rest to 50% of VO(2peak), despite greater elevations in BP in OA, the change in MCA V(mean) was greater in YA compared to OA (28% vs. 15%, respectively; P < 0.0005). In the YA, at intensities >70% of VO(2peak), the hyperventilation-induced declines in both P(ET)CO(2) (14 mmHg (YA) vs. 4 mmHg (OA); P < 0.05) and MCA V(mean) (-21% (YA) vs. -7% (OA); P < 0.0005) were greater in YA compared to OA. Our findings show (1), from rest-to-mild intensity exercise (50% VO(2peak)), elevations in CBF are reduced in OA and (2) age-related declines in hyperventilation during maximal exercise result in less hypocapnic-induced cerebral vasoconstriction.

Cerebral vasoreactivity in hypocapnia and hypercapnia in patients with diabetes mellitus type 2 with or without arterial hypertension.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is an in-dependent risk factor for cardiovascular diseases. The origin of diabetic microangiopathy is multifactorial; it affects all layers of the artery wall, causing endothelial and vasoreactivity impairment. The incidence of cerebral vasoreactivity failure in diabetic patients without stroke history is not precisely determined yet. The aim of the study was to assess the cerebrovascular reactivity in hypocapnia and hypercapnia in patients with type 2 DM with or without arterial hypertension without artery stenosis and stroke history, with the use of transcranial Doppler examination. MATERIAL AND METHODS: The mean blood flow velocity, pulsatility index and parameters of cerebrovascular reactivity were measured in 53 patients with type 2 DM (aged 42-72 years, mean 59.5 ± 7.9) and in 27 healthy volunteers (aged 36- 74 years, mean 57.0 ± 10.4). Diabetics were further divided into two subgroups according to the presence or absence of arterial hypertension. RESULTS: The index of cerebrovascular reactivity in hypocapnia and hypercapnia was significantly worse and time needed to normalization of blood flow velocity was significantly longer in patients with DM in comparison with healthy volunteers. CONCLUSIONS: Most DM type 2 patients without stroke history had decreased values of cerebral vasoreactivity parameters, which suggests the presence of microangiopathy.

Hypocapnia induced vasoconstriction significantly inhibits the neurovascular coupling in humans.

BACKGROUND/AIMS: Previous studies proved that vasodilation, caused by hypercapnia or acetazolamide, does not inhibit the visually evoked flow velocity changes in the posterior cerebral arteries. Our aim was to determine whether vasoconstriction induced by hypocapnia affects the neurovascular coupling. METHODS: By using a visual cortex stimulation paradigm, visually evoked flow velocity changes were detected by transcranial Doppler sonography in both posterior cerebral arteries of fourteen young healthy adults. The control measurement was followed by the examination under hyperventilation. Visual-evoked-potentials were also recorded during the control and hyperventilation phases. RESULTS: The breathing frequency increased from 16 ± 2 to 37 ± 3/min during hyperventilation, resulting in a decrease of the end-tidal CO(2) from 37 ± 3 to 25 ± 3 mm Hg and decrease of resting peak systolic flow velocity from 58 ± 11 to 48 ± 11 cm/s (p<0.01). To allow comparisons between volunteers, relative flow velocity was calculated in relation to baseline. Repeated measures analysis of variance revealed significant difference between the relative flow velocity time courses during hyper- and normoventilation (p<0.001). The maximum changes of visually evoked relative flow velocities were 26 ± 7% and 12 ± 5% during normoventilation and hyperventilation, respectively (p<0.01). Visual-evoked-potentials did not differ in the control and hyperventilation phases. CONCLUSION: The significantly lower visually evoked flow velocity changes but preserved visual-evoked-potential during hyperventilation indicates that the hypocapnia induced vasoconstriction significantly inhibits the neuronal activity evoked flow response.