Cerebral Blood Flow Index Research Articles

Transcranial Doppler Identification of Changing Autoregulatory Thresholds after Autoregulatory Impairment

OBJECTIVE Transcranial Doppler (TCD) flow velocity (FV) assessment may provide a useful index of autoregulatory impairment after severe head injury. It may define a therapeutic end point against which cerebral perfusion pressure (CPP) can be titrated. This study examines the relationship between cerebral blood flow (CBF) and TCD FV indices in a laboratory model before and after autoregulatory impairment. METHODS CPP, CBF, and middle cerebral artery TCD FV were measured continuously in nine anesthetized and ventilated sheep. CPP was decreased by hemorrhagic hypotension. The process was repeated after impairment of autoregulation by cisternal infusion, which maintained CPP at 0 mm Hg for 15 minutes. Points of significant change (i.e., breakpoints) from baseline values for each of the measured flow parameters were identified by using a ratio of variance technique. RESULTS Before any significant change in CBF or systolic TCD, diastolic TCD FV decreased (mean breakpoint, 69 mm Hg; range, 56–78 mm Hg) as CPP was reduced. This divergence of diastolic and systolic TCD FV, which occurred before autoregulatory failure, was associated with an increasing TCD pulsatility index (mean breakpoint, 63 mm Hg; range, 53–70 mm Hg). At diastolic TCD FV congruent with 10 cm/s, systolic TCD FV (mean breakpoint, 48 mm Hg; range, 46–53 mm Hg) and CBF (mean breakpoint, 49 mm Hg; range, 47–51 mm Hg) decreased rapidly, indicating autoregulatory failure. After autoregulatory impairment, the breakpoints for all four indices shifted to higher CPP values (mean, 16 mm Hg). CONCLUSION TCD FV assessment identified two CPP thresholds of autoregulatory loss. Before autoregulatory failure, an earlier phase of autoregulatory disturbance may be detected by divergent systolic and diastolic TCD FVs. It is important to note that this phase may be detected before CBF decreases. These TCD FV breakpoints depend on the state of autoregulatory impairment and may provide potential targets for CPP-directed therapy.

Transcranial Doppler Identification of Changing Autoregulatory Thresholds after Autoregulatory Impairment

Transcranial Doppler (TCD) flow velocity (FV) assessment may provide a useful index of autoregulatory impairment after severe head injury. It may define a therapeutic end point against which cerebral perfusion pressure (CPP) can be titrated. This study examines the relationship between cerebral blood flow (CBF) and TCD FV indices in a laboratory model before and after autoregulatory impairment. CPP, CBF, and middle cerebral artery TCD FV were measured continuously in nine anesthetized and ventilated sheep. CPP was decreased by hemorrhagic hypotension. The process was repeated after impairment of autoregulation by cisternal infusion, which maintained CPP at 0 mm Hg for 15 minutes. Points of significant change (i.e., breakpoints) from baseline values for each of the measured flow parameters were identified by using a ratio of variance technique. Before any significant change in CBF or systolic TCD, diastolic TCD FV decreased (mean breakpoint, 69 mm Hg; range, 56-78 mm Hg) as CPP was reduced. This divergence of diastolic and systolic TCD FV, which occurred before autoregulatory failure, was associated with an increasing TCD pulsatility index (mean breakpoint, 63 mm Hg; range, 53-70 mm Hg). At diastolic TCD FV congruent with 10 cm/s, systolic TCD FV (mean breakpoint, 48 mm Hg; range, 46-53 mm Hg) and CBF (mean breakpoint, 49 mm Hg; range, 47-51 mm Hg) decreased rapidly, indicating autoregulatory failure. After autoregulatory impairment, the breakpoints for all four indices shifted to higher CPP values (mean, 16 mm Hg). TCD FV assessment identified two CPP thresholds of autoregulatory loss. Before autoregulatory failure, an earlier phase of autoregulatory disturbance may be detected by divergent systolic and diastolic TCD FVs. It is important to note that this phase may be detected before CBF decreases. These TCD FV breakpoints depend on the state of autoregulatory impairment and may provide potential targets for CPP-directed therapy.

Prediction of secondary ischemic lesions with diffusion-weighted imaging after transient middle cerebral artery occlusion in rats

P75 Background and Purpose: Previous studies demonstrated that secondary ischemic lesions documented by diffusion-weighted imaging might be smaller than, larger than or similar to initial lesions that occur during ischemia. The purpose of this study was to investigate if the size of secondary lesions can be predicted. Methods: Twelve rats underwent 30 minutes of transient middle cerebral artery occlusion with the intraluminal suture method. Diffusion- and perfusion-weighted images were performed just before reperfusion, 90 minutes and 24 hours after reperfusion. The ischemic lesion size was calculated by tracing visual abnormalities on the apparent diffusion coefficient (ADC) maps. Cerebral blood flow index (CBF i ) ratio was calculated by dividing the ipsilateral CBF i by the contralateral CBF i . Based on difference between initial and secondary lesion volume, rats were assigned to reperfusion-benefit group (n=6) where secondary lesions were smaller than initial lesions (less than 85% of initial lesions) and reperfusion-nonbenefit group (n=6) where secondary lesions were similar to or larger than initial lesions (more than 85% of initial lesions). Results: At 90 minutes after reperfusion, the initial ischemic lesions almost disappeared in both groups. At 24 hours, secondary lesions were 54±11% (mean±SD) of the initial lesions in the reperfusion-benefit group and 100±14% of the initial lesions in the reperfusion-nonbenefit group (p<0.001). There was no difference in ADC values (47±2×10 -5 mm 2 /s vs 46±5×10 -5 mm 2 /s, p=0.7) and CBF i ratio (0.62±0.06 vs 0.67±0.04, p=0.2) between the two groups before reperfusion. However, the initial lesion volume was significantly smaller in the reperfusion-benefit group than in the reperfusion-nonbenefit group (125±54 mm 3 vs 195±36 mm 3 , p=0.037). Conclusions: Changes of ADC values and CBF before reperfusion are unable to predict if initial ischemic lesions will eventually shrink or not after reperfusion. Smaller size of initial lesions may suggest that secondary lesions will be smaller than initial lesions.

Temporal evolution of Diffusion / Perfusion Mismatch in a Rat Stroke Model

P69 Background and Purpose: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke. Studies show that lesions by PWI are sometimes larger than those of DWI in patients with acute ischemic stroke, suggests that the mismatch between DWI and PWI is potentially predictive of tissue at high risk for evolving into infarction. The aims of this study were to detect the evolution of the DWI/PWI mismatch in permanent focal experimental ischemia and transient focal experimental ischemia. Methods: Rats were subjected to permanent (n=8) and 60 minutes of temporary ischemia (n=8) using the intraluminal middle cerebral artery occlusion method and then underwent DWI and PWI after occlusion. Rats in the transient ischemic experiments were reperfused 60 minutes after occlusion. An apparent diffusion coefficient map and a cerebral blood flow index map were used to calculate the percent hemispheric lesion volume (%HLV) for each MRI parameter. Results: In permanent ischemia, %HLVs by DWI were 21%, 45%, 60%, 87%, and 101% of %HLV by PWI at 15, 30, 60, 90 and 120 minutes after ischemia, respectively. The ratio did not change after 120 minutes. With 60 minutes of temporary ischemia, the changes were almost the same as those in permanent ischemia before reperfusion. After reperfusion the lesions on PWI were smaller than those on DWI. The DWI lesion did not increase after reperfusion, and was the almost the same size as just before reperfusion. Conclusions: The DWI/PWI mismatch disappears at 2 hours after permanent ischemia, and the region of DWI/PWI mismatch can be saved from ischemic damage if reperfused early, but ischemic lesions seen on DWI can not be reduced by reperfusion after 60 minutes of temporary ischemia in this rat stroke model.

Human middle cerebral artery blood velocity during sexual intercourse.

Although the augmentation of central hemodynamics during human sexual intercourse is well established, dynamic changes in human regional cerebral blood flow have not been reported. Noninvasive transcranial Doppler ultrasonography has been well validated and allows direct, continuous measurement of phasic blood velocity in the human middle cerebral artery (a linear index of regional cerebral blood flow). The middle cerebral artery supplies the premotor and primary sensorimotor cortical regions for the arms, upper and lower trunk, and head. Blood velocities in this vessel have been shown to increase significantly with sensory stimuli and physical stresses. Accordingly, we tested the hypothesis that human sexual intercourse increases middle cerebral artery blood velocity. We used noninvasive, transcranial Doppler ultrasonography (95% confidence limits for precision +/- 7%) to measure blood velocity in the left middle cerebral artery of 10 male and 10 female, sexually acquainted, healthy adults (age range, 23 to 47 years; mean, 30 years). To eliminate signal artifacts and allow complete freedom of motion, a modified low profile, temporal fossa transducer was secured by minimal unobtrusive forehead strapping. Continuous measurements of phasic blood velocity and heart rate were made in a private bedroom setting during rest (control), preexcitement, excitation, prepenetration, penetration, preorgasm, orgasm, and resolution with the untethered instrumented subject in the supine missionary position. Heart rate and blood velocity responses were similar in both sexes. During orgasm, the maximal heart rate increased significantly (P < 0.05): 49 +/- 44% in women, 65 +/- 32% in men, and 58 +/- 38% combined from a combined resting value of 77 +/- 11 standard deviations SD beats per minute. Importantly, blood velocity in the middle cerebral artery of the 20 subjects remained unchanged (P > 0.10) from a resting value of 56 +/- 15 cm/s. In conclusion, in both sexes, human middle cerebral artery blood velocity, a linear index of human regional cerebral blood flow, does not increase significantly (P > 0.10) during human sexual intercourse.

Evaluation of the cerebral hemodynamic response to rhythmic handgrip.

The response of the cerebral circulation to exercise has been studied with transcranial Doppler ultrasound (TCD) because this modality provides continuous measurements of blood velocity and is well suited for the exercise environment. The use of TCD as an index of cerebral blood flow, however, requires the assumption that the diameter of the insonated vessel is constant. Here, we examine this assumption for rhythmic handgrip using a spectral index designed to measure trends in vessel flow. Nineteen normal subjects were studied during 5 min of volitional maximum rhythmic right handgrip at 1 Hz. TCD velocities from both middle arteries (left and right), blood pressure, and end-tidal PCO(2) were recorded every 10 s. A spectral weighted sum was also calculated as a flow index (FI). Averages were computed from the last 2 min of handgrip. Relative changes in velocity, FI, and pressure were calculated. The validity of FI was tested by comparing the change in diameter derived from equations relating flow and diameter. Mean blood pressure increased 23.8 +/- 17.8% (SD), and velocity increased 13.3 +/- 9.8% (left) and 9.6 +/- 8.3% (right). Although the mean change in FI was small [2.0 +/- 18. 2% (left) and 4.7 +/- 29.7% (right)], the variation was high: some subjects showed a significant increase in FI and others a significant decrease. Diameter estimates from two equations relating flow and luminal area were not significantly different. Decreases in FI were associated with estimated diameter decreases of 10%. Our data suggest that the cerebral blood flow (CBF) response to rhythmic handgrip is heterogeneous and that middle cerebral artery flow can decrease in some subjects, in agreement with prior studies using the Kety-Schmidt technique. We speculate that the velocity increase is due to sympathetically mediated vasoconstriction rather than a ubiquitous flow increase. Our data suggest that the use of ordinary TCD velocities to interpret the CBF response during exercise may be invalid.

Hypothermia for fulminant hepatic failure: A cool approach to a burning problem

Background Increased intracranial pressure as a complicationof acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. Methods We studied seven consecutivepatients aged 16–48 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32–33°C. Patients who were not suitable candidates for OLT (patients 1–3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37°C. Patients who were suitable candidates for OLT (patients 4–7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. Findings The four patients who were candidates for OLTwere successfully maintained until transplantation with 13 h (range 10–14 h) of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25–49 mm Hg) and was reduced in all patients to 16 (13–17) mm Hg (p < 0.05). Cerebral blood flow decreased from 103 (25–134) ml 100 g −1 mint before cooling to 44 (24–75) ml 100 g −1 min −1 after cooling (p < 0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 mm Hg (37–56) mm Hg to 70 (60–78) mm Hg (p < 0.05) and for cardiac index a decrease from 9.8 (7–13) to 5.1 (4.3–6.1) L per min per m 2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. Interpretation Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Temporal evolution of ischemic injury evaluated with diffusion-, perfusion-, and T2-weighted MRI.

Ischemic lesions seen on diffusion-weighted imaging (DWI) are reversible if reperfusion is performed within minutes after the onset of ischemia. This study was designed to determine whether acute reversibility of DWI abnormalities is transient following brief temporary focal brain ischemia and to characterize the temporal evolution of in vivo ischemic lesions. Eight rats were subjected to 30 minutes of temporary middle cerebral artery occlusion and underwent diffusion-, perfusion-, and T2-weighted MRI during occlusion; immediately after reperfusion; 30, 60, and 90 minutes after reperfusion; and 12, 24, 48, and 72 hours after reperfusion. Average apparent diffusion coefficient (ADCav) values and the cerebral blood flow index (CBFi) ratio were calculated in both the lateral caudoputamen and overlying cortex at each time point. The size of the in vivo ischemic abnormalities was calculated from the ADCav and the T2 maps. Postmortem triphenyltetrazolium chloride (TTC) staining was used to verify ischemic injury. Both the CBFi ratio and ADCav values declined significantly in the two regions during occlusion. The CBFi ratio recovered immediately after reperfusion and remained unchanged over 72 hours. However, ADCav values returned to normal at 60 to 90 minutes and secondarily decreased at 12 hours after reperfusion as compared with those in the contralateral hemisphere. The extent of the in vivo ischemic lesions maximized at 48 hours and was highly correlated with TTC-derived lesion size. Acute recovery of initial ADCav-defined lesions after reperfusion is transient, and secondary ADCav-defined lesions develop in a slow and delayed fashion.

Continuous assessment of cerebral autoregulation--clinical verification of the method in head injured patients.

Previously, using transcranial Doppler ultrasonography, we investigated whether the hemodynamic response to spontaneous variations in cerebral perfusion pressure (CPP) provides reliable information about cerebral autoregulatory reserve. In the present study we have verified this method in 166 patients after head trauma. Waveforms of intracranial pressure (ICP), arterial pressure and transcranial Doppler flow velocity (FV) were captured daily over 0.5-2.0 hour periods. Time-averaged mean flow velocity (FV) and CPP were resolved. The correlation coefficient indices between FV and CPP (Mx) were calculated over 3 minutes epochs, and averaged for each investigation. An index of CBF (flow velocity diastolic to mean ratio) was calculated independently for each investigation. Mx depended on CPP (p < 0.0001) increasing to positive values when CPP decreased below 60 mm Hg. This threshold coincided with an averaged breakpoint for autoregulation, expressed by the index of CBF. Mx depended on outcome following head injury stronger than the Glasgow Coma Score on admission (ANOVA, F values 18 and 15 respectively; N = 166). In patients who died, cerebral autoregulation was disturbed during the first two days following injury. These results indicate an important role for the continuous monitoring of autoregulation following head trauma.

Prediction of secondary ischemic lesions with diffusion-weighted imaging after transient middle cerebral artery occlusion in rats

P75 Background and Purpose: Previous studies demonstrated that secondary ischemic lesions documented by diffusion-weighted imaging might be smaller than, larger than or similar to initial lesions that occur during ischemia. The purpose of this study was to investigate if the size of secondary lesions can be predicted. Methods: Twelve rats underwent 30 minutes of transient middle cerebral artery occlusion with the intraluminal suture method. Diffusion- and perfusion-weighted images were performed just before reperfusion, 90 minutes and 24 hours after reperfusion. The ischemic lesion size was calculated by tracing visual abnormalities on the apparent diffusion coefficient (ADC) maps. Cerebral blood flow index (CBF i ) ratio was calculated by dividing the ipsilateral CBF i by the contralateral CBF i . Based on difference between initial and secondary lesion volume, rats were assigned to reperfusion-benefit group (n=6) where secondary lesions were smaller than initial lesions (less than 85% of initial lesions) and reperfusion-nonbenefit group (n=6) where secondary lesions were similar to or larger than initial lesions (more than 85% of initial lesions). Results: At 90 minutes after reperfusion, the initial ischemic lesions almost disappeared in both groups. At 24 hours, secondary lesions were 54±11% (mean±SD) of the initial lesions in the reperfusion-benefit group and 100±14% of the initial lesions in the reperfusion-nonbenefit group (p -5 mm 2 /s vs 46±5×10 -5 mm 2 /s, p=0.7) and CBF i ratio (0.62±0.06 vs 0.67±0.04, p=0.2) between the two groups before reperfusion. However, the initial lesion volume was significantly smaller in the reperfusion-benefit group than in the reperfusion-nonbenefit group (125±54 mm 3 vs 195±36 mm 3 , p=0.037). Conclusions: Changes of ADC values and CBF before reperfusion are unable to predict if initial ischemic lesions will eventually shrink or not after reperfusion. Smaller size of initial lesions may suggest that secondary lesions will be smaller than initial lesions.

Temporal evolution of Diffusion / Perfusion Mismatch in a Rat Stroke Model

P69 Background and Purpose: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke. Studies show that lesions by PWI are sometimes larger than those of DWI in patients with acute ischemic stroke, suggests that the mismatch between DWI and PWI is potentially predictive of tissue at high risk for evolving into infarction. The aims of this study were to detect the evolution of the DWI/PWI mismatch in permanent focal experimental ischemia and transient focal experimental ischemia. Methods: Rats were subjected to permanent (n=8) and 60 minutes of temporary ischemia (n=8) using the intraluminal middle cerebral artery occlusion method and then underwent DWI and PWI after occlusion. Rats in the transient ischemic experiments were reperfused 60 minutes after occlusion. An apparent diffusion coefficient map and a cerebral blood flow index map were used to calculate the percent hemispheric lesion volume (%HLV) for each MRI parameter. Results: In permanent ischemia, %HLVs by DWI were 21%, 45%, 60%, 87%, and 101% of %HLV by PWI at 15, 30, 60, 90 and 120 minutes after ischemia, respectively. The ratio did not change after 120 minutes. With 60 minutes of temporary ischemia, the changes were almost the same as those in permanent ischemia before reperfusion. After reperfusion the lesions on PWI were smaller than those on DWI. The DWI lesion did not increase after reperfusion, and was the almost the same size as just before reperfusion. Conclusions: The DWI/PWI mismatch disappears at 2 hours after permanent ischemia, and the region of DWI/PWI mismatch can be saved from ischemic damage if reperfused early, but ischemic lesions seen on DWI can not be reduced by reperfusion after 60 minutes of temporary ischemia in this rat stroke model.

Persistence of cerebral hemodynamic changes in patients with eclampsia: A report of three cases

Objective: This study was undertaken to compare the persistence of changes in estimated cerebral perfusion pressure and the resistance area product, an index of cerebrovascular resistance, in women with preeclampsia and women with eclampsia. Study Design: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasonography in 6 patients with severe preeclampsia and 3 women with eclampsia, and cerebral blood flow velocities were determined. Estimated cerebral perfusion pressure was calculated according to the following equation: Estimated cerebral perfusion pressure = Mean cerebral blood flow velocity/(Mean cerebral blood flow velocity – Diastolic cerebral blood flow velocity) × (Mean blood pressure – Diastolic blood pressure). Because the diameters of the vessels could not be measured directly, an index of resistance was calculated according to the following equation: Resistance area product = Mean blood pressure/Mean cerebral blood flow velocity. We calculated an index of cerebral blood flow according to the following equation: Index = Estimated cerebral perfusion pressure/Resistance area product. Patients were reassessed at 24 and 48 hours after delivery. Results: At the initial assessment the estimated cerebral perfusion pressure was higher in women with eclampsia than in those with severe preeclampsia. In addition, cerebrovascular resistance was significantly decreased in the eclampsia group, and it remained decreased as long as 4 days in 1 patient with eclampsia. Conclusions: Preeclampsia is associated with increases in cerebral perfusion pressure counterbalanced by increases in cerebrovascular resistance, with no change in cerebral blood flow. In eclampsia a significant increase in cerebral perfusion pressure occurs, but a significant fall in cerebrovascular resistance also occurs and a loss of autoregulation results in cerebral overperfusion similar to that of hypertensive encephalopathy. This may persist for as long as 4 days. (Am J Obstet Gynecol 1999;181:1162-5.)

Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure

Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.e.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 7 2 in the i. v. (+) group, 14 in the i. v.{-) group, 73 in the i. c.( + ) group, 7 5 in the i. c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. ( + ) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. ( + ), i.v.(-) and i.e. (-) groups and this change was mitigated in i.e. ( + ) group. HbO was reduced in i.e. (-) group and this decrease was attenuated in i.e. ( + ) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-a level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis. [Neurol Res 1999; 21: 391-398]

Prolonged dysequilibrium between blood and brain concentrations of propofol during infusions in sheep.

Previous work had shown dysequilibrium between the arterial blood and brain concentrations of the intravenous anaesthetic agent propofol following its rapid administration over 2 min to sheep. The extent of dysequilibrium was examined following slower administration as a constant rate 45-min infusion (10 mg/min). Six sheep were prepared with arterial and sagittal sinus (effluent from the brain) blood sampling catheters and a Doppler flow probe for measuring an index of cerebral blood flow. Propofol concentrations in arterial and sagittal sinus blood during and after the infusions were measured using high-performance liquid chromatography with fluorescence detection. Brain concentrations were calculated from these concentrations and cerebral blood flow using direct mass balance methods. There was dysequilibrium between the arterial blood and brain concentrations until approximately 30 min after the start of the infusion, with marked hysteresis between the arterial blood and brain concentrations for the duration of the study. The equilibrium half-life between the blood and the brain was 3.5 min, which is comparable to the value of 4.3 min derived from the earlier rapid administration data, suggesting there was no time dependency in the kinetics of cerebral uptake. The mass of propofol entering the brain via arterial blood was the same as the mass leaving the brain via sagittal sinus blood, suggesting minimal metabolism of propofol in the brain of sheep. It is clear that pharmacokinetic analysis based on arterial blood concentrations alone cannot accurately account for the concentrations of propofol at its site of action in the brain.

Changes in cerebral perfusion pressure in puerperal women with preeclampsia

Objective: To determine the variation in the estimated maternal cerebral perfusion and cerebrovascular resistance (the resistance area product) in the puerperium. Methods: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasound in ten women 2 days before labor, in 21 women in early labor and at 24 and 48 hours postpartum, and in 6 women at 1 week postpartum. Cerebral blood flow velocities were determined. Women were diagnosed initially with mild preeclampsia. Estimated cerebral perfusion pressure was V mean/[V mean − V diastolic] [BP mean − BP diastolic]. Because the diameter of the vessels could not be measured directly, an index of resistance was calculated: the resistance area product = BP mean/velocity mean. We calculated an index of cerebral blood flow to be estimated cerebral perfusion pressure divided by resistance area product. Our study had a power of 80% to detect a 16-cm/second increase in middle cerebral blood flow velocity. Results: Estimated maternal cerebral perfusion was maintained for up to 1 week postpartum. Cerebrovascular resistance did not change in the puerperium. Cerebral blood flow index (±standard deviation) was significantly increased at 1 week postpartum compared with early labor levels (28.3 ± 6.9 versus 46.7 ± 15.6, respectively) ( P < .05). Conclusion: Cerebral blood flow 1 week postpartum increased significantly over early labor values. These persistent changes in the cerebral vasculature might put patients at risk for seizures up to 1 week postpartum.

Changes in Cerebral Perfusion Pressure in Puerperal Women With Preeclampsia

In Brief Objective To determine the variation in the estimated maternal cerebral perfusion and cerebrovascular resistance (the resistance area product) in the puerperium. Methods The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasound in ten women 2 days before labor, in 21 women in early labor and at 24 and 48 hours postpartum, and in 6 women at 1 week postpartum. Cerebral blood flow velocities were determined. Women were diagnosed initially with mild preeclampsia. Estimated cerebral perfusion pressure was Vmean/[Vmean – Vdiastolic] [BPmean – BPdiastolic]. Because the diameter of the vessels could not be measured directly, an index of resistance was calculated: the resistance area product = BPmean/velocitymean. We calculated an index of cerebral blood flow to be estimated cerebral perfusion pressure divided by resistance area product. Our study had a power of 80% to detect a 16-cm/second increase in middle cerebral blood flow velocity. Results Estimated maternal cerebral perfusion was maintained for up to 1 week postpartum. Cerebrovascular resistance did not change in the puerperium. Cerebral blood flow index (±standard deviation) was significantly increased at 1 week postpartum compared with early labor levels (28.3 ± 6.9 versus 46.7 ± 15.6, respectively) (P < .05). Conclusion Cerebral blood flow 1 week postpartum increased significantly over early labor values. These persistent changes in the cerebral vasculature might put patients at risk for seizures up to 1 week postpartum. Changes in cerebral blood flow are maintained up to 1 week after delivery.

Efficacy of the stump pressure ratio as a guide to the safety of permanent occlusion of the internal carotid artery

To determine whether the absolute value for the stump pressure might be a useful index of symmetrical cerebral blood flow (CBF), and to examine correlations with the stump pressure ratio (initial mean stump pressure,preocclusion mean arterial pressure), fifty candidates for ICA injury or permanent occlusion were evaluated preoperatively. Each was continuously monitored for mean stump pressure and arterial pressure before, during (for a total of 20 min), and after balloon test occlusion. During the occlusion, CBF was measured by 99m Tc-hexamethyl-propyleneamine oxime (99m Tc-HMPAO) single photon emission computed tomography (SPECT). The stump pressure and the stump pressure ratio were then compared with the results of 99m Tc-HMPAO SPECT. Patients who failed to tolerate even briefperiods ofcarotid occlusion and showed asymmetric decreases in CBF on SPECT were divided into high and moderate risk groups. Those with no significant changes in CBF on the occluded site formed the minimum risk group. Mean stump pressure was over 50 mmHg in 10 of a total of25 patients in the high and moderate risk groups, and below 50 mmHg in 5 of the 25 patients in the minimum risk group. The stump pressure ratio did not exceed 56% in any bu~ two patients in the high and moderate risk groups, and values were at least 60% in all patients of the minimum. risk group. Decrease ofCBF in two moderate risk group cases was localized in the posterior circulation. Difference in symmetrical CBF between the stump pressure ratio vs. the absolute value ofmean stump pressure were statistically significant (p < 0.01, Fisher,s Exact Test). Maintenance ofa stump pressure ratio of60% or more during test occlusion may be a more useful index for a good collateral circulation than any absolute value for mean stump pressure. [Neural Res 1998; 20: 732–736]

The cerebral hemodynamic response to asphyxia and hypoxia in the near-term fetal sheep as measured by near infrared spectroscopy.

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.

Variation in cerebral perfusion pressure with different hypertensive states in pregnancy

Objective: Our purpose was to compare the estimated maternal cerebral perfusion pressure and an index of vascular resistance, the resistance area product, in nonpregnant women with hypertensive pregnant women. Study Design: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasonography in 17 nonpregnant women, 17 pregnant normotensive patients, 20 pregnant patients with chronic hypertension, and 21 pregnant patients with pre-eclampsia (defined by The American College of Obstetricians and Gynecologists criteria) and cerebral blood flow velocities were determined. We calculated estimated cerebral perfusion pressure as [Estimated cerebral perfusion pressure = V mean/(V mean = V diastolic) (Mean blood pressure – Diastolic blood pressure)] modified from Aaslid et al, 1986. Because the diameter of the vessels could not be measured directly, an index of resistance, the resistance area product, was calculated. Resistance area product = Mean blood pressure/mean velocity (Evans et al, 1988). We calculated an index of cerebral blood flow (Cerebral blood flow index) = Estimated cerebral perfusion pressure/resistance area product. Results: Women who were chronically hypertensive and those with pre-eclampsia showed a significant increase in estimated cerebral perfusion pressure and resistance area product compared with nonpregnant and pregnant normotensive women. An estimate of cerebral blood flow (cerebral blood flow index) in nonpregnant women showed that pregnancy resulted in a nonsignificant 18% increase in cerebral blood flow. Conclusions: Women with chronic hypertension and pre-eclampsia behave similarly by demonstrating significant increases in cerebral perfusion pressure (estimated cerebral perfusion pressure) and cerebrovascular resistance (resistance area product) compared with normotensive and nonpregnant women. Pregnant patients have a minimal increase in cerebral blood flow (18%). (Am J Obstet Gynecol 1998;179:1200-3.)