Changes In Cerebrovascular Resistance Research Articles

Static and dynamic analysis of cerebral blood flow in fifty-six large arterial vessel networks

Objective. The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset. Approach. We analysed a publicly available vessel dataset from a cohort of 56 (32/24F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort. Main results. Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (<6°) between blood pressure and blood flow at the cardiac frequency. Significance. These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

Mean arterial pressure during cerebral perfusion MRI: An arterial spin‐labeling study in younger and older adults

AbstractBackgroundHigh blood pressure (BP) and low cerebral blood flow (CBF) have been independently related to Alzheimer’s disease (AD) pathophysiology. Increased cerebrovascular resistance index (CVRi), the ratio of mean arterial pressure (MAP) to CBF, has also been linked to AD risk in older adults. Autoregulatory mechanisms maintain steady perfusion across a range of MAP values through changes in cerebrovascular resistance in healthy individuals. Age‐dependent cerebrovascular stiffening can disrupt cerebrovascular resistance, leaving the brain vulnerable to hypoperfusion with increased MAP. No studies have evaluated MAP during perfusion MRI to further evaluate whether high BP may be related to lower CBF, and whether this relationship is age‐dependent. We studied MAP during perfusion MRI in a sample of younger and older adults using an MRI‐compatible device to continuously monitor MAP.MethodCommunity‐dwelling older adults (n=21; age 56‐87) free of dementia or stroke, and healthy younger adults (n=16; age 18‐34) underwent resting pseudo‐continuous arterial spin‐labelling (pCASL)‐MRI to quantify CBF during simultaneous in‐scanner, continuous MAP monitoring. Average MAP and CBF were calculated over the 5 minute scan. Multiple linear regression examined the relationship between MAP and CBF for younger and older adults, controlling for age and sex.ResultOlder adults with higher MAP during perfusion MRI exhibited significantly lower CBF levels (R2 = .49, β = ‐.23, p = .02). MAP showed no significant relationship with CBF in younger adults.ConclusionThis is the first study to evaluate MAP during perfusion MRI. Findings indicate that higher MAP is correlated with lower CBF in real time in older adults only. We hypothesize that higher MAP may cause decreased CBF through chronic increases in cerebrovascular resistance. Our approach utilizes pCASL‐MRI, capturing CBF to capillaries and smaller arterioles that are susceptible to age‐related microvascular injury. It remains unclear whether the relationship between MAP and microvascular perfusion plays a role in the increased dementia risk associated with high CVRi, but increased CVRi and decreased CBF are associated with dementia. Future work will explore the role of BP during perfusion MRI and whether it may contribute to diagnosis, prognosis or treatment decision‐making to help prevent dementia.

Pulling back on the push-pull effect: use of lower body negative pressure to protect against drops in cerebral perfusion during airflight manoeuvres.

Pulling back on the push-pull effect: use of lower body negative pressure to protect against drops in cerebral perfusion during airflight manoeuvres.

Dissociation of Cerebral Blood Flow and Femoral Artery Blood Pressure Pulsatility After Cardiac Arrest and Resuscitation in a Rodent Model: Implications for Neurological Recovery.

BackgroundImpaired neurological function affects 85% to 90% of cardiac arrest (CA) survivors. Pulsatile blood flow may play an important role in neurological recovery after CA. Cerebral blood flow (CBF) pulsatility immediately, during, and after CA and resuscitation has not been investigated. We characterized the effects of asphyxial CA on short‐term (<2 hours after CA) CBF and femoral arterial blood pressure (ABP) pulsatility and studied their relationship to cerebrovascular resistance (CVR) and short‐term neuroelectrical recovery.Methods and ResultsMale rats underwent asphyxial CA followed by cardiopulmonary resuscitation. A multimodal platform combining laser speckle imaging, ABP, and electroencephalography to monitor CBF, peripheral blood pressure, and brain electrophysiology, respectively, was used. CBF and ABP pulsatility and CVR were assessed during baseline, CA, and multiple time points after resuscitation. Neuroelectrical recovery, a surrogate for neurological outcome, was assessed using quantitative electroencephalography 90 minutes after resuscitation. We found that CBF pulsatility differs significantly from baseline at all experimental time points with sustained deficits during the 2 hours of postresuscitation monitoring, whereas ABP pulsatility was relatively unaffected. Alterations in CBF pulsatility were inversely correlated with changes in CVR, but ABP pulsatility had no association to CVR. Interestingly, despite small changes in ABP pulsatility, higher ABP pulsatility was associated with worse neuroelectrical recovery, whereas CBF pulsatility had no association.ConclusionsOur results reveal, for the first time, that CBF pulsatility and CVR are significantly altered in the short‐term postresuscitation period after CA. Nevertheless, higher ABP pulsatility appears to be inversely associated with neuroelectrical recovery, possibly caused by impaired cerebral autoregulation and/or more severe global cerebral ischemia.

The Cerebrovascular Resistance in Combined Traumatic Brain Injury with Intracranial Hematomas.

The aim was to evaluate changes in cerebrovascular resistance (CVR) in combined traumatic brain injury (CTBI) in groups with and without intracranial hematomas (IH). Treatment outcomes in 70 patients with CTBI (42 males and 28 females) were studied. Mean age was 35.5 ± 14.8 years (range, 15-73). The patients were divided into two groups: group 1 included 34 CTBI patients without hematomas; group 2 comprised 36 patients with CTBI and IH. The severity according to the Glasgow Coma Scale averaged 10.4 ± 2.6 in group 1, and 10.6 ± 2.8 in group 2. All patients underwent perfusion computed tomography (CT) and transcranial Doppler of both middle cerebral arteries. Cerebral perfusion pressure and CVR were calculated. The mean CVR values in each group (both with and without hematomas) appeared to be statistically significantly higher than the mean normal value. Intergroup comparison of CVR values showed statistically significant increase in the CVR level in group 2 on the side of the removed hematoma (р = 0.037). CVR in the perifocal zone of the removed hematoma remained significantly higher compared with the symmetrical zone in the contralateral hemisphere (p = 0.0009). CVR in patients with CTBI is significantly increased compared to the normal value and remains elevated after evacuation of hematoma in the perifocal zone compared to the symmetrical zone in the contralateral hemisphere. This is indicative of certain correlation between the mechanisms of cerebral blood flow autoregulation and maintaining CVR.

Lack of linear correlation between dynamic and steady-state cerebral autoregulation.

Key points For correct application and interpretation of cerebral autoregulation (CA) measurements in research and in clinical care, it is essential to understand differences and similarities between dynamic and steady‐state CA.The present study found no correlation between dynamic and steady‐state CA indices in healthy older adults.There was variability between individuals in all (steady‐state and dynamic) autoregulatory indices, ranging from low (almost absent) to highly efficient CA in this healthy population.These findings challenge the assumption that assessment of a single CA parameter or a single set of parameters can be generalized to overall CA functioning. Therefore, depending on specific research purposes, the choice for either steady‐state or dynamic measures or both should be weighed carefully. The present study aimed to investigate the relationship between dynamic (dCA) and steady‐state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid artery (ICA) and vertebral artery (VA) and CBF velocity at the middle cerebral artery (MCA). With CVR = BP/CBF, Slope‐CVRICA, Slope‐CVRVA and Slope‐CVRiMCA were derived. dCA was assessed (i) in supine rest, analysed with transfer function analysis (gain and phase) and autoregulatory index (ARI) fit from spontaneous oscillations (ARIBaseline), and (ii) with transient changes in BP using a bolus injection of SNP (ARISNP) and PhE (ARIPhE). Comparison of sCA and dCA parameters (using Pearson's r for continuous and Spearman's ρ for ordinal parameters) demonstrated a lack of linear correlations between sCA and dCA measures. However, comparisons of parameters within dCA and within sCA were correlated. For sCA slope‐CVRVA with Slope‐CVRiMCA (r = 0.45, P < 0.03); for dCA ARISNP with ARIPhE (ρ = 0.50, P = 0.03), ARIBaseline (ρ = 0.57, P = 0.03) and PhaseLF (ρ = 0.48, P = 0.03); and for GainVLF with GainLF (r = 0.51, P = 0.01). By contrast to the commonly held assumption based on an earlier study, there were no linear correlations between sCA and dCA. As an additional observation, there was strong inter‐individual variability, both in dCA and sCA, in this healthy group of elderly, in a range from low to high CA efficiency.

Changes in arterial cerebral blood volume during lower body negative pressure measured with MRI

Cerebral Autoregulation (CA), defined as the ability of the cerebral vasculature to maintain stable levels of blood flow despite changes in systemic blood pressure, is a critical factor in neurophysiological health. Magnetic resonance imaging (MRI) is a powerful technique for investigating cerebrovascular function, offering high spatial resolution and wide fields of view (FOV), yet it is relatively underutilized as a tool for assessment of CA. The aim of this study was to demonstrate the potential of using MRI to measure changes in cerebrovascular resistance in response to lower body negative pressure (LBNP). A Pulsed Arterial Spin Labeling (PASL) approach with short inversion times (TI) was used to estimate cerebral arterial blood volume (CBVa) in eight healthy subjects at baseline and −40mmHg LBNP. We estimated group mean CBVa values of 3.13 ± 1.00 and 2.70 ± 0.38 for baseline and lbnp respectively, which were the result of a differential change in CBVa during −40mmHg LBNP that was dependent on baseline CBVa. These data suggest that the PASL CBVa estimates are sensitive to the complex cerebrovascular response that occurs during the moderate orthostatic challenge delivered by LBNP, which we speculatively propose may involve differential changes in vascular tone within different segments of the arterial vasculature. These novel data provide invaluable insight into the mechanisms that regulate perfusion of the brain, and establishes the use of MRI as a tool for studying CA in more detail.

Dopamine therapy does not affect cerebral autoregulation during hypotension in newborn piglets.

BackgroundHypotensive neonates who have been treated with dopamine have poorer neurodevelopmental outcome than those who have not been treated with dopamine. We speculate that dopamine stimulates adrenoceptors on cerebral arteries causing cerebral vasoconstriction. This vasoconstriction might lead to a rightward shift of the cerebral autoregulatory curve; consequently, infants treated with dopamine would have a higher risk of low cerebral blood flow at a blood pressure that is otherwise considered “safe”.MethodsIn anaesthetized piglets, perfusion of the brain, monitored with laser-doppler flowmetry, and cerebral venous saturation was measured at different levels of hypotension. Each piglet was studied in two phases: a phase with stepwise decreases in MAP and a phase with stepwise increases in MAP. We randomized the order of the two phases, whether dopamine was given in the first or second phase, and the infusion rate of dopamine (10, 25, or 40 μg/kg/min). In/deflation of a balloon catheter, placed in vena cava, induced different levels of hypotension. At each level of hypotension, fluctuations in MAP were induced by in/deflations of a balloon catheter in descending aorta.ResultsDuring measurements, PaCO2 and arterial saturation were stable. MAP levels ranged between 14 and 82 mmHg. Cerebral autoregulation (CA) capacity was calculated as the ratio between %-change in cerebrovascular resistance and %-change in MAP induced by the in/deflation of the arterial balloon. A breakpoint in CA capacity was identified at a MAP of 38±18 mmHg without dopamine and at 44±18, 31±14, and 24±14 mmHg with dopamine infusion rates of 10, 25, and 40 μg/kg/min (p = 0.057). Neither the index of steady-state cerebral perfusion nor cerebral venous saturation were affected by dopamine infusion.ConclusionDopamine infusion tended to improve CA capacity at low blood pressures while an index of steady-state cerebral blood flow and cerebral venous saturation were unaffected by dopamine infusion. Thus, dopamine does not appear to impair CA in newborn piglets.

Change in Cerebrovascular Resistance as Diagnostic Index of Cerebral Hemodynamics in Patients with Severe Combined Traumatic Brain Injury

Change in Cerebrovascular Resistance as Diagnostic Index of Cerebral Hemodynamics in Patients with Severe Combined Traumatic Brain Injury

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66±6years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR=MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11±7% during SNP, and increased by 21±8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the VA; no differences in CA were found between the ICA and VA. CA slopes measured at the VA had positive correlations with the total and periventricular WMH volume (r=0.55 and 0.59, P<0.01). Collectively, these findings demonstrated the presence of large individual variability of CA in older adults, and that, when measured in the posterior cerebral circulation, it is the higher rather than lower CA reactivity that is associated with WMH severity.

Effects of a Dietary Beetroot Juice Treatment on Systemic and Cerebral Haemodynamics- A Pilot Study.

Beetroot Juice (BJ) contains dietary nitrates that increase the blood Nitric Oxide (NO) level, decrease Blood Pressure (BP), increase athletic performance and improve cognitive functions but the mechanism remains unclear. Ultrasonographic measurement of middle cerebral artery blood flow velocity with computation of Cerebral Augmentation Index (CAIx) is a measure of the reflected flow signal, modulated by changes in cerebrovascular resistance and compliance. This pilot study tests the hypothesis that ingestion of an amount of BJ sufficient to raise the blood NO level two-to three-fold, decreases Transcranial Doppler (TCD) measured CAIx. Ten healthy young-adult African-American women were studied at two levels of submaximal exercise, 40% and 80% of their predetermined peak oxygen consumptions. The subjects ingested nitrate-free orange juice (OJ, control) and an isocaloric BJ beverage (1.5 mg/mL nitrate, 220 Cal), on different days, 1-2 weeks apart. The BJ treatment increased blood NO and decreased systolic BP at rest and at the two levels of exercise. The BJ treatment decreased CAIx only at the two levels of exercise (from 79 ± 2% to 62 ± 2% and from 80 ± 2% to 60 ± 3%, p<0.05). Exercise increased TCD-measured resistance and pulsatility indices (RIx, PIx) without changing AIx. The BJ treatment had no effect on RIx and PIx. These findings suggest that decreased CAIx associated with aerobic exercise reflects the change in cerebral haemodynamics resulting from dietary nitrate supplementation. Future studies should determine whether the BJ-induced decrement in CAIx is correlated with an improvement in brain function.

Monitoring of cerebral autoregulation.

Pressure autoregulation is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure (CPP). Static autoregulation represents how far cerebrovascular resistance changes when CPP varies, and dynamic autoregulation represents how fast these changes happen. Both have been monitored in the setting of neurocritical care to aid prognostication and contribute to individualizing CPP targets in patients. Failure of autoregulation is associated with a worse outcome in various acute neurological diseases. Several studies have used transcranial Doppler ultrasound, intracranial pressure (ICP with vascular reactivity as surrogate measure of autoregulation), and near-infrared spectroscopy to continuously monitor the impact of spontaneous fluctuations in CPP on cerebrovascular physiology and to calculate derived variables of autoregulatory efficiency. Many patients who undergo such monitoring demonstrate a range of CPP in which autoregulatory efficiency is optimal. Management of patients at or near this optimal level of CPP is associated with better outcomes in traumatic brain injury. Many of these studies have utilized the concept of the pressure reactivity index, a correlation coefficient between ICP and mean arterial pressure. While further studies are needed, these data suggest that monitoring of autoregulation could aid prognostication and may help identify optimal CPP levels in individual patients.

Assessing cerebrovascular autoregulation from critical closing pressure and resistance area product during upright posture in aging and hypertension.

Static cerebral autoregulation (sCA) is believed to be resistant to aging and hypertensive pathology. However, methods to characterize autoregulation commonly rely on beat-by-beat mean hemodynamic measures and do not consider within-beat pulse wave characteristics that are impacted by arterial stiffening. We examined the role of critical closing pressure (CrCP) and resistance area product (RAP), two measures derived from the pulse wave, across supine lying, sitting, and standing postures in young adults, normotensive older adults, and older adults with controlled and uncontrolled hypertension (N = 80). Traditional measures of sCA, using both intracranial and extracranial methods, indicated similar efficiency across all groups, but within-beat measures suggested different mechanisms of regulation. At rest, RAP was increased in hypertension compared with young adults (P < 0.001), but CrCP was similar. In contrast, the drop in CrCP was the primary regulator of change in cerebrovascular resistance upon adopting an upright posture. Both CrCP and RAP demonstrated group-by-posture interaction effects (P < 0.05), with older hypertensive adults exhibiting a rise in RAP that was absent in other groups. The posture-related swings in CrCP and RAP were related to changes in both the pulsatile and mean components of arterial pressure, independent of age, cardiac output, and carbon dioxide. Group-by-posture differences in pulse pressure were mediated in part by an attenuated heart rate response in older hypertensive adults (P = 0.002). Examination of pulsatile measures in young, elderly, and hypertensive adults identified unique differences in how cerebral blood flow is regulated in upright posture.

Dynamic cerebral pressure‐flow relationships in aging and long‐term heart transplant recipients (1068.11)

Long‐term heart transplant recipients (HTR) provide a unique opportunity to examine the relationship between the cerebrovascular and cardiovascular systems. We examined the hypothesis that HTR would have cerebral pressure‐flow responses more comparable to control subjects matched to the age of their cerebrovasculature than their donor hearts. Eight male clinically stable HTR (62 ± 8 yrs of age and 9 ± 7 yrs post transplant), 9 male age‐matched controls (AM: 63 ± 8 yrs) and 10 male donor controls (DC: 27 ± 5 yrs), were tested. Each test involved: seated rest (5‐min), and squat‐stand maneuvers at 0.05 and 0.10 Hz. The BRS and pressure‐flow responses were assessed with TFA. BRS TFA revealed that the HTR had reductions in R‐R interval PSD and LF gain (P&lt;0.01) compared to both control groups. There were comparable TFA cerebral pressure‐flow responses for all groups at all frequencies with coherence and phase. The pressure‐flow gain was significantly greater in DC than both AM and HTR at all frequencies (P&lt;0.05). Cerebrovascular resistance (CVR) was negatively correlated with pressure‐flow gain at all frequencies (P&lt;0.05). These results reveal that pressure‐flow coherence and phase are comparable throughout aging, potentially helping HTR compensate for reductions in BRS. Although pressure‐flow gain did decrease in the HTR and AM, it was related to changes in CVR highlighting the need cautiously interpret this metric.Grant Funding Source: Supported by NSERC

Cerebral autoregulation, individual variability, and white matter hyperintensity (1069.1)

Purpose: To assess regional cerebral autoregulation (CA) and its association with white matter hyperintensities (WMH) in older adults.Methods: Twenty‐seven healthy older subjects (13 females, 68 ± 6 yr) underwent fluid‐attenuated inversion recovery MRI to measure WMH. Cerebral blood flow (CBF) in the internal carotid (ICA) and vertebral arteries (VA) was measured using color‐coded duplex ultrasonography. CA was assessed during steady‐state changes in mean arterial pressure (MAP) from ‐11 ± 7% to 21 ± 8% (relative to baseline) and quantified by a linear regression slope between percentage changes in cerebrovascular resistance (CVR=MAP/CBF) and MAP. Multiple linear regression analysis was used to explore the relationship between regional CA and WMH.Results: Substantial individual CA variability was found in both ICA and VA with the regression slopes of CVR to MAP ranged from 0.366 to 2.198 in the ICA and from 0.172 to 3.175 in the VA. CA measured in the VA had a positive correlation (r = 0.741, P &lt; 0.001) with periventricular WMH (PWMH), after adjustment for age, central arterial stiffness, sex and resting blood pressure. Of note, individuals with more PWMH (&gt; 0.3 % intracranial volume) showed a hyper‐reactivity of CA (i.e., a paradoxical reduction in CBF during increases in arterial pressure) at the VA. Interpretation: Large individual CA variability exists in healthy older adults. The association between the hyper‐reactivity of posterior CA and PWMH suggests that the presence of small cerebral vessel disease may lead to hypoperfusion in the posterior cerebral circulation during acute increase in blood pressure.Grant Funding Source: NIH grant R01AG033106‐01 and R01HL102457.

Cerebrovascular time constant in patients suffering from hydrocephalus

Objectives: We studied possible link between cerebrospinal fluid (CSF) compensation and indices describing pulsatile inflow of cerebral arterial blood.Methods: A total of 50 infusion tests performed in patients with symptoms of normal pressure hydrocephalus (NPH) were examined retrospectively. Waveforms of CSF pressure, noninvasive arterial blood pressure (ABP), and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) were used to estimate relative changes in cerebral arterial compliance (Ca) and cerebrovascular resistance (CVR). Product of Ca and CVR, called cerebral arterial time constant (τ, unit: seconds), was calculated at the baseline and plateau phase of the test and compared with CSF compensatory parameters such as resistance to CSF outflow, elasticity, slope of amplitude–pressure line, and pulse amplitude of CSF pressure.Results: Neither of CSF compensatory parameters correlated with hemodynamic indices. However, the change in cerebral perfusion pressure (CPP) provoked change in τ (R = 0·33; P = 0·017) secondary to a change in CVR (R = 0·81; P < 0·0001). Changes in CVR and Ca had a reciprocal character (R = −0·64; P < 0·0001) with magnitude of variation in CVR (68%) prevailing over magnitude of changes in Ca (49%).Discussion: Hemodynamics of pulsatile inflow of cerebral arterial blood assessed by cerebral arterial time constant is not directly linked to dynamics of CSF circulation and pressure–volume compensation but is sensitive to changes in CPP during infusion test.

Noninvasive Autoregulation Monitoring in a Swine Model of Pediatric Cardiac Arrest

Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest. Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n = 8) or 2 days (n = 8), or that had undergone sham surgery with 2 days of recovery (n = 8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n = 5) or sham surgery (n = 5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter. The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percentage change in cerebrovascular resistance divided by the percentage change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury. In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA in comparison with laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension.

Cerebrovascular time constant: dependence on cerebral perfusion pressure and end-tidal carbon dioxide concentration

Objective: The cerebrovascular time constant (τ) describes the time to establish a change in cerebral blood volume after a step transient in arterial blood pressure (ABP). We studied the relationship between τ, ABP, intracranial pressure (ICP), and end-tidal carbon dioxide concentration (EtCO2).Method: Recordings from 46 anaesthetized, paralysed and ventilated New Zealand rabbits were analysed retrospectively. ABP was directly monitored in the femoral artery, transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) from the basilar artery, and ICP using an intraparenchymal sensor. In nine animals end-tidal CO2 (EtCO2) was monitored continuously. ABP was decreased with injection of trimetophan (n = 11) or haemorrhage (n = 6) and increased by boluses of dopamine (n = 11). ICP was increased by infusion of normal saline into the lumbar cerebrospinal fluid space (n = 9). Changes in cerebral compliance (Ca) were estimated as a ratio of the pulse amplitude of the cerebral arterial blood volume (CBV) and the pulse amplitude of ABP. Changes in cerebrovascular resistance (CVR) were expressed as mean ABP or cerebral perfusion pressure (CPP) divided by mean CBFV. Time constant τ was calculated as the product of CVR and Ca.Results: The time constant changed inversely to the direction of the change in ABP (during arterial hypo- and hypertension) and CPP (during intracranial hypertension). Ca increased with decreasing CPP, while CVR decreased. During a decrease in CPP, changes in Ca exceeded changes in CVR. In contrast, during hypercapnia, the decrease in CVR was more pronounced than the increase in Ca, resulting in a decreasein τ.Conclusion: Cerebrovascular time constant τ is modulated by ABP, ICP, and EtCO2.

Increases in cerebrovascular impedance in older adults

This study explored a novel method for measuring cerebrovascular impedance to quantify the relationship between pulsatile changes in cerebral blood flow (CBF) and arterial pressure. Arterial pressure in the internal or common carotid artery (applanation tonometry), CBF velocity in the middle cerebral artery (transcranial Doppler), and end-tidal CO(2) (capnography) were measured in six young (28 ± 4 yr) and nine elderly subjects (70 ± 6 yr). Transfer function method was used to estimate cerebrovascular impedance. Under supine resting conditions, CBF velocity was reduced in the elderly despite the fact that they had higher arterial pressure than young subjects. As expected, cerebrovascular resistance index was increased in the elderly. In both young and elderly subjects, impedance modulus was reduced gradually in the frequency range of 0.78-8 Hz. Phase was negative in the range of 0.78-4.3 Hz and fluctuated at high frequencies. Compared with the young, impedance modulus increased by 38% in the elderly in the range of 0.78-2 Hz and by 39% in the range of 2-4 Hz (P < 0.05). Moreover, increases in impedance were correlated with reductions in CBF velocity. Collectively, these findings demonstrate the feasibility of assessing cerebrovascular impedance using the noninvasive method developed in this study. The estimated impedance modulus and phase are similar to those observed in the systemic circulation and other vascular beds. Moreover, increases in impedance in the elderly suggest that arterial stiffening, besides changes in cerebrovascular resistance, contributes to reduction in CBF with age.

Renin Angiotensin System Gene Polymorphisms and Cerebral Blood Flow Regulation

Our objective was to investigate the associations between polymorphisms in representative genes of the renin angiotensin system with measures of cerebral blood flow regulation in older adults. Participants in this analysis were white subjects (n=335) in the MOBILIZE Boston study (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston), an observational study of community-dwelling elders who underwent transcranial Doppler while sitting and standing and during hypercapnea and hypocapnea. Autoregulation phenotype was the change in cerebrovascular resistance from sit to stand. Vasoreactivity phenotype was the slope of the change in cerebrovascular conductance versus change in end-tidal CO2. A total of 33 tagged single nucleotide polymorphisms were selected in the angiotensinogen gene, the angiotensin converting enzyme gene, and the angiotensin receptor gene. Regression analyses adjusted for age, gender, body mass index, mean arterial blood pressure, stroke, and use of antihypertensives were conducted for each single nucleotide polymorphism and outcome. Bonferroni corrections were used to adjust P values for multiple testing. In the angiotensinogen gene, only the rs699 single nucleotide polymorphism was associated with vasoreactivity after Bonferroni correction (P=0.00028). Homozygous carriers of the CC genotype of this single nucleotide polymorphism had lower vasoreactivity compared with the CT or TT genotypes. There were no significant associations with autoregulation measures. None of the single nucleotide polymorphisms in the other genes were associated with our phenotypes. This analysis suggests that the angiotensinogen gene may be involved in vasoreactivity independent of blood pressure. Larger studies are needed to confirm the role of this gene in cerebrovascular health and aging.