Reduction In Cerebral Blood Flow Velocity Research Articles

Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion.

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Effect of CGRP inhibitors on interictal cerebral hemodynamics in individuals with migraine.

Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics. In 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated. CA was similar off and on treatment, in the MCA (p = 0.42) and PCA (p = 0.72). CVR was also unaffected by treatment, in the MCA (p = 0.38) and PCA (p = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1-12.4; p = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9-10.3; p = 0.04). Dynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test

BackgroundThe physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood.Methods and ResultsWe evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end‐tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30‐minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5‐minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age‐ and sex‐matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P≥0.4). The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (−7.8% versus −1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P=0.027) and a greater increase in symptom scores at study completion (interaction, P<0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end‐tidal carbon dioxide) did not differ between groups after PCST (all P>0.05).ConclusionsReduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.

Reduction of Cerebral Mean Blood Flow Velocity and Oxygenation After High-Volume (1.5 mL kg−1) Caudal Block in Infants

Background We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined ‘the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. Methods Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (CRSO2) were followed during 5 min after the initial caudal injection (1.5 ml kg−1, ropivacaine 0.2%) in 12 infants Results The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation CRSO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. Conclusion High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to ‘the CSF rebound mechanism' for secondary spread of high-volume caudal block.

Brain blood flow and hyperventilation on cold water immersion: can treading water help control these symptoms of cold shock?

Cold-water immersion (CWI) elicits the cold shock response (CSR). The hyperventilatory component of the CSR causes a decrease in cerebral blood flow velocity (CBFv) potentially causing sensations of dizziness and increasing the risk of becoming unconscious and consequently drowning [1]. In these early minutes of CWI the current advice is to 'float first' and remain stationary [2] yet this strategy may not have any effect on ventilation and therefore brain CBFv. We tested the hypothesis that leg only exercise could offset the reduction in CBFv in a resting CWI (H1) and be absent in warm water immersion.

Cerebral oxygenation in health and disease.

Monitoring cerebral blood flow (CBF) and oxygenation has implications for both clinical practice and research interests; e.g., to provide insight into functional neurovascular coupling, to better understand orthostatic hypotension, and to evaluate the influence of vasopressors on cerebral oxygenation during anesthesia and/or surgery. These topics, and others, are addressed in this e-book by presenting original research, reviews, and opinion papers covering new, exciting but also controversial issues related to cerebral oxygenation in health and disease as evaluated by near-infrared spectroscopy (NIRS).

Reduction of cerebral mean blood flow velocity and oxygenation after high-volume (1.5 ml kg−1) caudal block in infants

We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined 'the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (C(R)SO2) were followed during 5 min after the initial caudal injection (1.5 ml kg(-1), ropivacaine 0.2%) in 12 infants <3 months of age. The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation C(R)SO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to 'the CSF rebound mechanism' for secondary spread of high-volume caudal block.

Difference in cerebral blood flow velocity in neonates with and without hyperbilirubinemia

PurposeTo evaluate the difference in cerebral blood flow velocity (CBFV) in neonates with and without hyperbilirubinemia. MethodsCBFV of 70 healthy late-preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the threshold of phototherapy requirement was compared with 70 gestational- and postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in internal carotid, vertebral and middle cerebral arteries by transcranial color Doppler ultrasound at the beginning of phototherapy, after 48–72h of starting phototherapy and at 5–7days after its stoppage. In controls CBFV was assessed once at inclusion. ResultsBoth the groups were comparable. An increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was observed in the UCH group. A further increase in CBFV was noticed after 48h of phototherapy. After 5–7days of stoppage of phototherapy, though there was a significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ⩽25mg/dL), in severe UCH (serum bilirubin >25mg/dL), CBFV remained increased. Four neonates developed features of acute bilirubin encephalopathy and had significantly higher CBFV compared to those with normal outcome. ConclusionsAn increase in CBFV was observed in neonates with UCH compared to those without hyperbilirubinemia.

Exercise plus volume loading prevents orthostatic intolerance but not reduction in cerebral blood flow velocity after bed rest

This study tested the hypothesis that reduction in cerebral blood flow (CBF) during orthostatic stress after bed rest can be ameliorated with volume loading, exercise, or both. Transcranial Doppler was used to measure changes in CBF velocity during lower body negative pressure (LBNP) before and after an 18-day bed rest in 33 healthy subjects. Subjects were assigned into four groups with similar age and sex: 1) supine cycling during bed rest (Exercise group; n = 7), 2) volume loading with Dextran infusion after bed rest to restore reduced left ventricular filling pressure (Dextran group; n = 7), 3) exercise combined with volume loading to prevent orthostatic intolerance (Ex-Dex group; n = 7), and 4) a control group (n = 12). LBNP tolerance was measured using a cumulative stress index (CSI). After bed rest, CBF velocity was reduced at a lower level of LBNP in the Control group, and the magnitude of reduction was greater in the Ex-Dex group. However, reduction in orthostatic tolerance was prevented in the Ex-Dex group. Notably, volume loading alone prevented greater reductions in CBF velocity after bed rest, but CSI was reduced still by 25%. Finally, decreases in CBF velocity during LBNP were correlated with reduction in cardiac output under all conditions (r(2) = 0.86; P = < 0.001). Taken together, these findings demonstrate that volume loading alone can ameliorate reductions in CBF during LBNP. However, the lack of associations between changes in CBF velocity and orthostatic tolerance suggests that reductions in CBF during LBNP under steady-state conditions by itself are unlikely to be a primary factor leading to orthostatic intolerance.

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.

Intensive Blood Pressure Control Affects Cerebral Blood Flow in Type 2 Diabetes Mellitus Patients

Type 2 diabetes mellitus is associated with microvascular complications, hypertension, and impaired dynamic cerebral autoregulation. Intensive blood pressure (BP) control in hypertensive type 2 diabetic patients reduces their risk of stroke but may affect cerebral perfusion. Systemic hemodynamic variables and transcranial Doppler-determined cerebral blood flow velocity (CBFV), cerebral CO2 responsiveness, and cognitive function were determined after 3 and 6 months of intensive BP control in 17 type 2 diabetic patients with microvascular complications (T2DM+), in 18 diabetic patients without (T2DM-) microvascular complications, and in 16 nondiabetic hypertensive patients. Cerebrovascular reserve capacity was lower in T2DM+ versus T2DM- and nondiabetic hypertensive patients (4.6±1.1 versus 6.0±1.6 [P<0.05] and 6.6±1.7 [P<0.01], Δ%mean CBFV/mm Hg). After 6 months, the attained BP was comparable among the 3 groups. However, in contrast to nondiabetic hypertensive patients, intensive BP control reduced CBFV in T2DM- (58±9 to 54±12 cm·s(-1)) and T2DM+ (57±13 to 52±11 cm·s(-1)) at 3 months, but CBFV returned to baseline at 6 months only in T2DM-, whereas the reduction in CBFV progressed in T2DM+ (to 48±8 cm·s(-1)). Cognitive function did not change during the 6 months. Static cerebrovascular autoregulation appears to be impaired in type 2 diabetes mellitus, with a transient reduction in CBFV in uncomplicated diabetic patients on tight BP control, but with a progressive reduction in CBFV in diabetic patients with microvascular complications, indicating that maintenance of cerebral perfusion during BP treatment depends on the progression of microvascular disease. We suggest that BP treatment should be individualized, aiming at a balance between BP reduction and maintenance of CBFV.

Relationship Between Ventilatory Threshold and Cerebral Blood Flow During Maximal Exercise in Humans

Background: This work studied the relationship between changes in cerebral blood flow velocity (CBFV) through the middle cerebral artery (MCA) with non-invasive ventilatory threshold (VT) measurements determined by gas- exchange during upright maximal cycle ergometry. Methods: Fourteen (M=8, F=6) healthy, young (23.1 ± 3.9 yr) participants volunteered for this study and performed a cy- cle ergometer protocol to maximal exertion. The CBFV was monitored continuously through the MCA by transcranial Doppler ultrasound and was assessed at rest, VT, and at maximal exertion (VO2max). Ventilatory threshold was assessed using three common methods: 1) V-slope, 2) nadir of the ventilatory equivalent for carbon dioxide production (VE/VCO2), and 3) maximal partial pressure of carbon dioxide (PETCO2). Results: Analysis of variance demonstrated significant (p<0.001) main effects for CBFV, volume of oxygen consumed (VO2), volume of carbon dioxide produced (VCO2), and PETCO2. Bonferroni post hoc analysis demonstrated an increase in CBFV from rest to a peak CBFV (p<0.01) with a decrease from peak CBFV to VO2max (p<0.01). Stepwise linear re- gression suggest the only predictor of a reduction in CBFV during maximal exercise is the nadir of VE/VCO2 (p<0.01). Conclusion: These data demonstrate an increase in CBFV during dynamic upright exercise up to approximately 78% VO2max after which CBFV decreases significantly to VO2max. This decrease in CBFV was closely related to common non-invasive measures of ventilatory threshold suggesting a close relationship between cerebral blood flow and the threshold for ventilatory compensation.

Hypohydration and prior heat stress exacerbates decreases in cerebral blood flow velocity during standing

Hypohydration is associated with orthostatic intolerance; however, little is known about cerebrovascular mechanisms responsible. This study examined whether hypohydration reduces cerebral blood flow velocity (CBFV) in response to an orthostatic challenge. Eight subjects completed four orthostatic challenges (temperate conditions) twice before (Pre-EU and Pre-Hyp) and following recovery from passive heat stress ( approximately 3 h at 45 degrees C, 50% relative humidity, 1 m/s air speed) with (Post-EU) or without (Post-Hyp) fluid replacement of sweat losses (-3% body mass loss). Measurements included CBFV, mean arterial pressure (MAP), heart rate (HR), end-tidal CO(2), and core and skin temperatures. Test sessions included being seated (20 min) followed by standing (60 s) then resitting (60 s) with metronomic breathing (15 breaths/min). CBFV and MAP responses to standing were similar during Pre-EU and Pre-Hyp. Standing Post-Hyp exacerbated the magnitude (-28.0 +/- 1.4% of baseline) and duration (9.0 +/- 1.6 s) of CBFV reductions and increased cerebrovascular resistance (CVR) compared with Post-EU (-20.0 +/- 2.1% and 6.6 +/- 0.9 s). Standing Post-EU also resulted in a reduction in CBFV, and a smaller decrease in CVR compared with Pre-EU. MAP decreases were similar for Post-EU (-18 +/- 4 mmHg) and Post-Hyp (-21 +/- 5 mmHg) from seated to standing. These data demonstrate that despite similar MAP decreases, hypohydration, and prior heat stress (despite apparent recovery) produce greater CBFV reduction when standing. These observations suggest that hypohydration and prior heat stress are associated with greater reductions in CBFV with greater CVR, which likely contribute to orthostatic intolerance.

Cerebral effects of nitrous oxide during isoflurane-induced hypotension in the pig

We have studied the effects of nitrous oxide on cerebral blood flow (CBF), cerebral blood flow velocity (CBFV) and intracranial pressure (ICP) during isoflurane-induced hypotension in 10 pigs. CBF was measured using laser Doppler flowmetry, CBFV in the right middle cerebral artery was calculated using Doppler ultrasound and ICP was measured using an extradural ICP monitor. Each animal was studied under four conditions, examined sequentially: (i) mean intra-arterial pressure (MAP) 85 mm Hg, maintained with isoflurane, (ii) MAP 50-55 mm Hg, induced by isoflurane only, (iii) MAP 85 mm Hg, maintained with isoflurane and 50% nitrous oxide, and (iv) MAP 50-55 mm Hg, induced by isoflurane and 50% nitrous oxide. No significant differences were noted between conditions with respect to ICP. There was a significant difference in CBF during condition (ii) compared with (i) (mean 75(SD 21) vs 100(0)%) and during condition (iv) compared with (iii) (90(26) vs 109(13)%). Animals under condition (iv) exhibited a 20% reduction in CBFV compared with those under condition (iii) (57 vs 69 cm s-1). For animals under normotensive conditions, addition of nitrous oxide to isoflurane resulted in a 16% increase in CBFV (69 vs 60 cm s-1). Comparing isoflurane-induced hypotension ((ii) vs (iv)), there was no statistical difference in either CBF or CBFV on addition of 50% nitrous oxide. The correlation between changes in CBF and CBFV was not significant. We conclude that the use of nitrous oxide during isoflurane-induced hypotension has no significant effect on CBF, CBFV or ICP compared with the use of isoflurane alone.

Aminophylline therapy and cerebral blood flow velocity in preterm infants.

Pulsed Doppler ultrasound was used to evaluate the cerebral blood flow velocity (CBFV), in the middle and anterior cerebral arteries in 10 infants before and after the administration of aminophylline (7.5 mg/kg). Mean CBFV, heart rate, blood pressure, oxygen and carbon dioxide tensions were recorded before the loading dose, and then at 1, 2, 6 and 24 h after completion of the infusion. Mean CBFV in the middle and anterior cerebral arteries were 16.8 cm/s and 10.8 cm/s respectively prior to the infusion. There was a significant decrease (P < 0.05) in velocities in both arteries at 1 and 2h post drug therapy, which returned to base values by 6 h, and remained as such at 24 h. The heart rate increased (P < 0.05) after the infusion, while no consistent changes were observed in blood pressure or oxygen tension. Carbon dioxide levels were significantly reduced (P < 0.05) at 2 h. The reduction in CBFV, however, was more than would be expected on the basis of the change in carbon dioxide levels alone, suggesting that other factors may be exerting an influence. While no adverse effects were noted in the infants studied, it is suggested that aminophylline should be used judiciously in sick preterm infants at highest risk from ischaemic brain injury.

Aminophylline Reduces Cerebral Blood Flow Velocity in Low-Birth-Weight Infants

Cerebral blood flow decreases substantially in the adult after a single bolus injection of aminophylline. To determine if the cerebral circulation of the low-birth-weight infant behaves in a similar manner, we measured cerebral blood flow velocity (CBFV) in the anterior cerebral arteries of nine infants treated with an intravenous bolus dose of 5 mg/kg of body weight of aminophylline. A reduction in CBFV of 21% and 17% was observed at 60 and 120 minutes following the aminophylline administration. There was a concurrent substantial reduction in PCO2 from 45 +/- 7 to 39 +/- 7 mm Hg before and 120 minutes after the aminophylline administration, respectively. The reduction in CBFV may be the result of a reduction in PCO2 resulting from aminophylline treatment.