Differences In Cerebral Autoregulation Research Articles

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Holding up under pressure: a complex interplay between cerebral blood flow and ventilatory responses to alterations in carbon dioxide.

Holding up under pressure: a complex interplay between cerebral blood flow and ventilatory responses to alterations in carbon dioxide.

Comparison of Autoregulation Index during Sit‐To‐Stand in Young Healthy Individuals across Races

Cerebral autoregulation is an important mechanism to protect the brain by maintaining the brain perfusion over varying blood pressures. The cerebral blood flow velocity response to Sit‐To‐ Stand maneuver has been widely used to assess dynamic cerebral autoregulation. Previous work has demonstrated sex differences in autoregulation; however, little is known about the impact of race. Potential racial differences in cerebral autoregulation may contribute to different incidences of cerebrovascular events between different races. Therefore, the purpose of this study was to compare the Autoregulatory index between four different racial groups. We enrolled 55 young healthy subjects (aged 18~35 years) with four racial groups, i.e. White/Caucasian (Age 27±5; n=11; 5 Males), Black/African American (Age 28±6; n=8; 4 Males), Latino (Age 28±6; n=6; 2 Males), and Asian (Age 27±3; n=30; 15 Males). The transcranial Doppler was used to continuously record the cerebral blood flow velocity at middle cerebral artery during 3 repeated sit‐to‐stand maneuvers, with simultaneous measurements of blood pressure, heart rate, and end‐tidal CO2 (ETCO2). There was no difference in demographic variables across groups except for BMI (24±4, 26±4, 27±5, and 23±3; kg/m2, P=0.043). Similarly, there were no differences in baseline cerebral blood flow velocity, blood pressure or heart rate with the exception of ETCO2 (35±3, 40±4, 35±3, and 38±3 mmHg, P=0.003). We found no differences between groups in the physiological response during sit‐to‐stand. Similarly, autoregulatory index was similar across all racial groups (3.6±2.4, 3.9±1.2, 3.3±2.6, and 3.6±1.5, P=0.948). These data suggest that cerebral autoregulation is similar in young healthy individuals across different races. However, these findings must be interpreted with caution due to the small number of participants in the various racial groups. Future studies are warranted to include larger sample size, older subjects and also to consider sex differences within each race.Support or Funding InformationSupported by the Funding from Rutgers University and U.S. Department of Defense.

Sex differences in cerebral autoregulation are unaffected by menstrual cycle phase in young, healthy women.

Sex is known to affect the prevalence of conditions such as stroke. However, effects of sex on cerebral blood flow regulation are still not well understood. Critical to this understanding is how fluctuations in hormones across the menstrual cycle affect cerebral autoregulation. We measured autoregulation in the early follicular, late follicular, and midluteal phases during spontaneous and induced blood pressure oscillations in 26 young, healthy individuals (13 women and 13 men, age: 26 ± 4 yr). Men participated three times, ~1-3 wk apart. Beat-by-beat blood pressure, heart rate, end-tidal CO2, and transcranial Doppler ultrasonography of the middle (MCA) and anterior (ACA) cerebral arteries were obtained. We did not find a difference in cerebral autoregulation across the menstrual cycle in women but found significantly improved autoregulation in the MCA and ACA of women compared with men. Women demonstrated significantly lower MCA gain (0.97 ± 0.13 vs. 1.17 ± 0.14%/mmHg, P = 0.001), higher MCA phase (46.1 ± 12.6 vs. 35.8 ± 7.9°, P = 0.019), and higher ACA phase (40.5 ± 10.8 vs 31.5 ± 8.5°, P = 0.040) during repeated squat-to-stand maneuvers. Women also had lower MCA gain (1.50 ± 0.11 vs. 1.72 ± 0.30%/mmHg, P = 0.029) during spontaneous fluctuations in pressure while standing and less of a decrease in MCA flow velocity (-18.7 ± 2.7 vs. -23.2 ± 6.0%, P = 0.014) during sit-to-stand maneuvers. Our results suggest that young women have improved cerebral autoregulation compared with young men regardless of menstrual cycle phase and that autoregulation is relatively robust to acute fluctuations in female sex hormones. NEW & NOTEWORTHY This is the first study to investigate thoroughly the effects of menstrual cycle phase and sex differences in cerebral autoregulation in young, healthy individuals. Cerebral autoregulation was unaffected by menstrual cycle phase during both repeated squat-to-stand and sit-to-stand maneuvers. However, women demonstrated significantly improved cerebral autoregulation in the middle and anterior cerebral arteries, suggesting women were able to maintain cerebral blood flow during changes in blood pressure more efficiently than men.

Are there differences in cerebral autoregulation between small increases or decreases of blood pressure? (1184.7)

Cerebral blood flow velocity (CBFV) in the middle cerebral and arterial blood pressure (ABP) were recorded while a pseudorandom sequence of lower body negative pressure (LBNP) steps was applied for approximately 5 minutes in 31 healthy adult volunteers (53 recodings). The LBNP provoked ABP changes of 4.5 ± 4.1 mmHg (mean ± standard deviation). Cerebral autoregulation (CA) was quantified from phase at 0.1 Hz, calculated over the whole recording (Pwhole) and then only over segments with increasing or decreasing LBNP (Plbnp2, Plbnp1), respectively. Phase was also estimated over all signal segments with only increasing (or only decreasing) ABP (Pabp1, Pabp2) ‐ whether spontaneous or provoked. The results showed small, but significant differences between the estimates (Friedman, p<0.0001), with the largest mean values for Pabp1 and Pabp2. There was no significant difference (Wilcoxon) between Pabp1 and Pabp2, or between Plbnp1 and Plbnp2, but all were significantly different to Pwhole. There was no significant difference in dispersion from the mean, between phase estimates from different signal segments. The results thus indicate that the response to small increases or decreases in LBNP and ABP are similar. The data also provides further evidence that some signal segments within a recording are more suitable for CA analysis than others. Selection of only the segments with increasing or decreasing LBNP was not beneficial.Grant Funding Source: Supported by EPSRC (UK)

Hemispheric Differences in Cerebral Autoregulation in Children with Moderate and Severe Traumatic Brain Injury

To examine hemispheric differences in cerebral autoregulation in children with traumatic brain injury (TBI). After IRB approval and consent, subjects underwent static cerebral autoregulation testing during the first 9 days after PICU admission. Cerebral autoregulation was quantified using the autoregulatory index (ARI). Forty-two (27 M:15 F) children (10 +/- 5 years) with TBI and admission Glasgow coma scale score (5 +/- 2) were enrolled. Seven (54%) of the 13 children with focal TBI and 8 (28%) of 29 children with diffuse TBI had impairment or absence of cerebral autoregulation of at least one hemisphere. In patients with isolated focal TBI, ARI was lower (0.40 +/- 0.40 vs. 0.67 +/- 0.40; P = 0.03) in the side of TBI than in the unaffected hemisphere, but cerebral autoregulation was often impaired on the side without TBI or shift (5/13) on head CT. There was no difference in ARI between hemispheres in children with diffuse TBI, with or without superimposed focal lesions (P = 0.17). Patients with bilateral intact cerebral autoregulation tended to have higher 6 month Glasgow Outcome Score (GOS) than patients with either unilateral or bilateral cerebral autoregulation impairment (GOS 4.0 +/- 0.60 vs. 3.6 +/- 0.80; P = 0.08). Hemispheric differences in cerebral autoregulation were common in children with isolated focal TBI. Absence of TBI on CT was not always associated with intact cerebral autoregulation. Patients with bilaterally intact cerebral autoregulation tended to have better outcomes.

Gender Differences in Cerebral Blood Flow Velocity and Autoregulation between the Anterior and Posterior Circulations in Healthy Children

There is little information on gender differences in cerebral autoregulation. The purpose of this study was to compare autoregulation of the anterior and posterior circulations using the tilt test method in healthy boys and girls who were 10-16 y of age. Transcranial Doppler was used to measure middle cerebral artery and basilar artery flow velocities (Vmca and Vbas). Cerebral autoregulation (ARI) of the middle cerebral (ARImca) and basilar arteries (ARIbas) was examined using the tilt test method. An ARI <0.4 indicates impaired autoregulation. Among the 13 boys and 13 girls, Vmca and Vbas were higher in girls. All children demonstrated intact autoregulation, but boys had higher ARImca than girls, whereas girls had higher ARIbas than boys. Girls demonstrated greater autoregulation in the basilar artery, whereas boys demonstrated greater autoregulation in the middle cerebral artery. Girls had higher flow velocities in both vessels. This study provides normative data on cerebral autoregulation of the posterior circulation in healthy, awake boys and girls.

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Altered cerebral circulation, as reported during normal pregnancy, and in patients with pre-eclampsia, can be associated with changes in cerebral vascular reactivity and/or cerebral autoregulation. The aim of our study was to perform a comparative assessment of cerebral haemodynamics, including vascular reactivity and autoregulation, in pre-eclamptic patients, healthy pregnant women, and healthy non-pregnant women. Thirty patients with pre-eclampsia were recruited. Age- and height-matched healthy pregnant (n=30) and non-pregnant control (n=30) groups were also recruited. Monitoring included transcranial Doppler ultrasonography, end-tidal carbon dioxide and non-invasive arterial pressure measurement. Cerebral autoregulation was assessed by performing the transient hyperaemic response (THR) test. The cerebrovascular reactivity to carbon dioxide (CRCO(2)) was assessed by measuring middle cerebral artery blood flow velocity (MCAFV) after induced changes in end-tidal carbon dioxide. Estimated cerebral perfusion pressure (eCPP) and critical closing pressure (CrCP) were calculated using established formulae. Statistical analysis included ANOVA with Tukey's pairwise comparisons. Mean arterial pressure (MAP) was increased in pre-eclampsia (P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05), but in pre-eclampsia it was similar to the non- pregnant group. When compared with the non-pregnant group, mean eCPP was higher in the healthy pregnant and pre-eclamptic groups (P<0.05). There were no meaningful differences in cerebral autoregulation or CRCO(2). Healthy pregnancy increases eCPP, presumably by decreasing CrCP. In pre-eclampsia, eCPP is maintained at the same level as in healthy pregnancy despite an increased MAP. Pre-eclampsia has no significant effect on cerebral autoregulation or CRCO(2).

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Altered cerebral circulation, as reported during normal pregnancy, and in patients with pre-eclampsia, can be associated with changes in cerebral vascular reactivity and/or cerebral autoregulation. The aim of our study was to perform a comparative assessment of cerebral haemodynamics, including vascular reactivity and autoregulation, in pre-eclamptic patients, healthy pregnant women, and healthy non-pregnant women.Thirty patients with pre-eclampsia were recruited. Age- and height-matched healthy pregnant (n=30) and non-pregnant control (n=30) groups were also recruited. Monitoring included transcranial Doppler ultrasonography, end-tidal carbon dioxide and non-invasive arterial pressure measurement. Cerebral autoregulation was assessed by performing the transient hyperaemic response (THR) test. The cerebrovascular reactivity to carbon dioxide (CRCO(2)) was assessed by measuring middle cerebral artery blood flow velocity (MCAFV) after induced changes in end-tidal carbon dioxide. Estimated cerebral perfusion pressure (eCPP) and critical closing pressure (CrCP) were calculated using established formulae. Statistical analysis included ANOVA with Tukey's pairwise comparisons.Mean arterial pressure (MAP) was increased in pre-eclampsia (P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05), but in pre-eclampsia it was similar to the non- pregnant group. When compared with the non-pregnant group, mean eCPP was higher in the healthy pregnant and pre-eclamptic groups (P<0.05). There were no meaningful differences in cerebral autoregulation or CRCO(2).Healthy pregnancy increases eCPP, presumably by decreasing CrCP. In pre-eclampsia, eCPP is maintained at the same level as in healthy pregnancy despite an increased MAP. Pre-eclampsia has no significant effect on cerebral autoregulation or CRCO(2).

Cerebral blood flow and resistances during hypotensive haemorrhage in the rabbit: transcranial Doppler and laser‐Doppler flowmetry

Transcranial Doppler (TCD) determined cerebral blood flow velocity and laser Doppler flowmetry (LDF) measured cortical perfusion were simultaneously assessed during hypotensive haemorrhage in 15 anaesthetized rabbits. Systolic (Fsys), diastolic (Fdia) and mean (Fmean) blood flow velocities were recorded into the intracranial internal carotid (ICA) and basilar artery (BA). Resistance (RI = Fsys-Fdia/Fsys) and pulsatility (PI = Fsys-Fdia/Fmean) indices were calculated. Step decreases of 10 mmHg of mean arterial pressure (MAP) from 80 to less than 30 mmHg provoked a fall of LDF signal below 50 mmHg. Blood velocities decreased into BA below 40 mmHg, and below 50 mmHg into ICA indicating regional differences in cerebral autoregulation. Cortical resistances (resLDF = MAP/LDF) fell below 60 mmHg whereas RI and PI increased when MAP decreased into BA below 40 mmHg and ICA below 50 mmHg. A weak correlation was found between Fmean and LDF (BA: r = 0.55, P < 0.01 and ICA = 0.46, P < 0.01). Both RI and PI were poorly correlated to resLDF into BA (RI-resLDF: r = -0.39, P < 0.01; PI-resLDF: r = -0.39, P < 0.01) and ICA (RI-resLDF: r = -0.18, ns; PI-resLDF: r = -0.22, ns). Pulse pressure (systolic-diastolic pressure) correlated with RI (ICA: r = -0.62, P < 0.001; BA: r = -0.61, P < 0.001) and PI (ICA: r = -0.61, P < 0.001; BA: r = -0.62, P < 0.001). In conclusion, during haemorrhagic shock, TCD correlates with LDF and indicates regional differences in autoregulatory settings. However, Doppler indices do not reflect the changes in cerebral resistances because they are influenced by the changes in pulsatile pressure.