Cerebral Cortical Oxygenation Research Articles

Meta-Analysis of the Correlation between Postoperative Cognitive Dysfunction and Intraoperative Cerebral Oxygen Saturation.

Objective This study is aimed at performing a meta-analysis for discussing the association between postoperative cognitive dysfunction (POCD) and cerebral cortical oxygen saturation after surgery (rSO2). Method Search common English databases such as Cochrane Library, PubMed, and Embase databases to evaluate the quality of all references. According to the normalized mean difference (SMD) and 95% confidence interval calculated by the revman5 software, the correlation between reported POCD and rSO2 was evaluated. The retrieval time is up to February 1, 2021. Results A total of 7 randomized controlled trials and 564 POCD patients were included in the study, with follow-up duration of 1-12 months. All patients were divided into control and operation subgroups. In the subgroup analysis of elderly patients, abdominal surgery, and orthopedic surgery, the mean intraoperative cerebral oxygen saturation of patients with POCD was significantly lower than those of patients without POCD (I2 = 55%, SMD = −0.57). Conclusion Lower intraoperativersO2 was associated with reduced incidence of neurological complications and renal alure as well as the length of stay in the intensive care unit and the total hospital stay.

Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults

Cocoa flavanols protect humans against vascular disease, as evidenced by improvements in peripheral endothelial function, likely through nitric oxide signalling. Emerging evidence also suggests that flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized double-blind within-subject acute study in healthy young adults, we link these two lines of research by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation responses to hypercapnia, as well as higher performance only when cognitive demand is high. Individual difference analyses further show that participants who benefit from flavanols intake during hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They further show the importance of studies combining physiological and graded cognitive challenges in young adults to investigate the actions of dietary flavanols on brain function.

Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis

Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48 h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins, but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective.

Cerebral hemodynamics during graded Valsalva maneuvers.

The Valsalva maneuver (VM) produces large and abrupt changes in mean arterial pressure (MAP) that challenge cerebral blood flow and oxygenation. We examined the effect of VM intensity on middle cerebral artery blood velocity (MCAv) and cortical oxygenation responses during (phases I–III) and following (phase IV) a VM. Healthy participants (n = 20 mean ± SD: 27 ± 7 years) completed 30 and 90% of their maximal VM mouth pressure for 10 s (order randomized) whilst standing. Beat-to-beat MCAv, cerebral oxygenation (NIRS) and MAP across the different phases of the VM are reported as the difference from standing baseline. There were significant interaction (phase * intensity) effects for MCAv, total oxygenation index (TOI) and MAP (all P < 0.01). MCAv decreased during phases II and III (P < 0.01), with the greatest decrease during phase III (−5 ± 8 and −19 ± 15 cm·s−1 for 30 and 90% VM, respectively). This pattern was also evident in TOI (phase III: −1 ± 1 and −5 ± 4%, both P < 0.05). Phase IV increased MCAv (22 ± 15 and 34 ± 23 cm·s−1), MAP (15 ± 14 and 24 ± 17 mm Hg) and TOI (5 ± 6 and 7 ± 5%) relative to baseline (all P < 0.05). Cerebral autoregulation, indexed, as the %MCAv/%MAP ratio, showed a phase effect only (P < 0.001), with the least regulation during phase IV (2.4 ± 3.0 and 3.2 ± 2.9). These data illustrate that an intense VM profoundly affects cerebral hemodynamics, with a reactive hyperemia occurring during phase IV following modest ischemia during phases II and III.

Assessment of dynamic cerebral autoregulation and cerebrovascular CO2 reactivity in ageing by measurements of cerebral blood flow and cortical oxygenation

With ageing, cerebral blood flow velocity (CBFV) decreases; however, to what extent dynamic cerebral autoregulation and cerebrovascular CO2 reactivity are influenced by ageing is unknown. The aim was to examine the dynamic responses of CBFV and cortical oxygenation to changes in blood pressure (BP) and arterial CO2 across different ages. Fifty-eight participants in three age groups were included, as follows: young (n=20, 24±2years old), elderly (n=20, 66±1years old), and older elderly (n=18, 78±3years old). The CBFV was measured using transcranial Doppler ultrasound, simultaneously with oxyhaemoglobin (O2Hb) using near-infrared spectroscopy and beat-to-beat BP measurements using Finapres. Postural manoeuvres were performed to induce haemodynamic fluctuations. Cerebrovascular CO2 reactivity was tested with hyperventilation and CO2 inhalation. With age, CBFV decreased (young 59±12cms(-1), elderly 48±7cms(-1) and older elderly 42±9cms(-1), P<0.05) and cerebrovascular resistance increased (1.46±0.58, 1.81±0.36 and 1.98±0.52mmHgcm(-1)s(-1), respectively, P<0.05). Normalized gain (autoregulatory damping) increased with age for BP-CBFV (0.88±0.18, 1.31±0.30 and 1.06±0.34, respectively, P<0.05) and CBFV-O2Hb (0.10±0.09, 0.12±0.04 and 0.17±0.08, respectively, P<0.05) during the repeated sit-stand manoeuvre at 0.05Hz. Even though the absolute changes in CBFV and cerebrovascular resistance index during the cerebrovascular CO2 reactivity were higher in the young group, the percentage changes in CBFV, cerebrovascular resistance index and O2Hb were similar in all age groups. In conclusion, there was no decline in dynamic cerebral autoregulation and cerebrovascular CO2 reactivity with increasing age up to 86years. Despite the decrease in cerebral blood flow velocity and increase in cerebrovascular resistance with advancing age, CBFV and cortical oxygenation were not compromised in these elderly humans during manoeuvres that mimic daily life activities.

Cerebral Near-Infrared Spectroscopy to Evaluate Anti-G Straining Maneuvers in Centrifuge Training

Over the past decade, near-infrared spectroscopy (NIRS) has emerged as an easily manageable noninvasive method for the continuous monitoring of cerebral cortical oxygenation during +Gz exposure. NIRS is also used to evaluate pilot trainees' ability to adequately perform anti-G straining maneuvers in the course of centrifuge training. This study aimed to determine the general patterns and individual differences in NIRS recordings during +Gz exposure. There were 22 healthy male cadets who participated in the study. The centrifuge training profiles included a gradual onset run (GOR, onset rate of 0.1 Gz x s(-1)) and short-term repeated exposures, with Gz levels from 4 to 7 Gz at an onset rate of 1.0 Gz x s(-1) (rapid onset run, ROR). Cortical tissue hemoglobin saturation (tissue oxygenation index, TOI) and changes in the concentration of oxygenated hemoglobin (O2Hb) were recorded from the right forehead during the period of Gz exposure. Most of the subjects successfully performed an anti-G straining maneuver and maintained or increased the cerebral oxygenation level during Gz exposure. In four subjects, however, oxygenation decline was observed at levels over 4 Gz, even though their anti-G systems were functioning. In contrast to the O2Hb response, TOI, which reflects intracranial oxygenation changes, was decreased during the anti-G straining maneuver at Gz onset or during the countdown to a ROR exposure. Although NIRS is an effective tool for monitoring anti-G straining maneuver performance, it should be carefully evaluated in terms of intracranial oxygenation results.

Oscillations in cerebral blood flow and cortical oxygenation in Alzheimer's disease

In Alzheimer's disease (AD) cerebrovascular function is at risk. Transcranial Doppler, near-infrared spectroscopy, and photoplethysmography are noninvasive methods to continuously measure changes in cerebral blood flow velocity (CBFV), cerebral cortical oxygenated hemoglobin (O(2)Hb), and blood pressure (BP). In 21 patients with mild to moderate AD and 20 age-matched controls, we investigated how oscillations in cerebral blood flow velocity (CBFV) and O(2)Hb are associated with spontaneous and induced oscillations in blood pressure (BP) at the very low (VLF = 0.05 Hz) and low frequencies (LF = 0.1 Hz). We applied spectral and transfer function analysis to quantify dynamic cerebral autoregulation and brain tissue oxygenation. In AD, cerebrovascular resistance was substantially higher (34%, AD vs. control: Δ = 0.69 (0.25) mm Hg/cm/second, p = 0.012) and the transmission of very low frequency (VLF) cerebral blood flow (CBF) oscillations into O(2)Hb differed, with increased phase lag and gain (Δ phase 0.32 [0.15] rad; Δ gain 0.049 [0.014] μmol/cm/second, p both < 0.05). The altered transfer of CBF to cortical oxygenation in AD indicates that properties of the cerebral microvasculature are changed in this disease.

β2 Adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats

Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats. Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)]. Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus. Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension.

Evaluation of Cerebral Oxygenation During Electrophysiological Studies

To assess cerebral cortical oxygenation and cellular homeostasis during EPS and RF ablation, using near infrared spectroscopy. Standard EPS was performed in 11 sedated patients (female = 6, mean age = 45 ± 11 years) with symptomatic SVT documented on ECG and no pre-existing cardiovascular or cerebrovascular disease. A NIRO-300 spectrophotometer was used to continuously measure absolute changes in the concentrations of chromophores which reflect intravascular and mitochondrial levels of oxygenation, namely oxygenated haemoglobin (hbo2), deoxygenated haemoglobin (Hb) and the net redox status of cytochrome c oxidase (cyt-a,a3). MABP was monitored simultaneously. RF ablations were performed on 10 patients [AV nodal reentrant tachycardia=6; AV reentrant tachycardia= 4; cycle length = 348 ± 69 msec (range: 225-425 msec)]. No significant changes occurred in hbo2, Hb and cyt-a,a3 during atrial and ventricular EPS pacing protocols, induced SVT, or RF ablation. MABP decreased during pacing at cycle lengths < 400 msec (p<0.005). Cellular energy dynamics were stable during atrial and ventricular pacing, SVT, and RF ablation. This data suggests that overall cerebral tissue oxygenation is preserved during EPS.

Cerebral Oxygenation During Defibrillator Threshold Testing of Implantable Cardioverter Defibrillators

The induction of ventricular fibrillation (VF) during defibrillator threshold testing of implantable cardioverter defibrillators (ICD) provokes global cerebral hypoperfusion and impaired oxygen delivery. Limited data are available on the neurophysiological effects of defibrillator threshold testing. Near infrared spectroscopy (NIRS) can noninvasively measure changes in specific chromophores, which reflect cerebral oxygenation at the intravascular and mitochondrial levels. We performed a prospective trial using NIRS to analyze cerebral cortical oxygenation during defibrillator threshold testing. Eleven patients (men = 9; age = 64 +/- 11 years: LVEF = 44 +/- 11%) underwent subpectoral ICD implantation and defibrillator threshold testing under general anesthesia. A NIRO 300 spectrometer was used to measure the absolute changes in the concentrations of oxyhemoglobin, de-oxyhemoglobin, and cytochrome c oxidase copper moiety during each procedure. The mean arterial blood pressure was monitored simultaneously. The mean number of defibrillator threshold tests was two (range 2-6). Twenty-six episodes of VF (duration 13.1 +/- 9.7 seconds; cycle length 230.2 +/- 20.8 ms) and two episodes of VT (duration 15 +/- 2.8 seconds; cycle length 320 +/- 11.3 ms) were induced. Each episode of VF and VT resulted in a decrease in the mean arterial blood pressure to 23.9 +/- 7.5 mmHg (p < or = 0.05) and oxyhemoglobin (-4.2 +/- 1.7 micromol/L; p < or = 0.05) and an increase in de-oxyhemoglobin (2.7 +/- 1.4 micromol/L). There was no change in the cytochrome c oxidase copper moiety redox status (0.09 +/- 0. 30 micromol/L). Our results suggest that impaired oxygen delivery during induced VF and VT does not affect oxygen availability at the cellular intra-mitochondrial level.

Effect of cardiopulmonary bypass on cortical cerebral oxygenation during coronary artery bypass grafting.

To investigate the changes in cerebral oxygenation during coronary artery bypass grafting (CABG) with normothermic cardiopulmonary bypass (CPB) using near infrared spectroscopy. Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated haemoglobin [HHb], oxygenated haemoglobin [O(2)Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue haemoglobin index (THI). Measurements were performed in 19 consecutive patients undergoing normothermic (34-36 degrees C) CPB. Data were recorded at 0.5s intervals and averaged into 30 s epochs. Data analysis was carried at baseline, 1, 20, and 40 min after start of CPB, at rewarming, on weaning from CPB, and at closing of chest. There were no in-hospital death, neurological deficits, or myocardial infarcts. Compared to baseline, during the entire CPB duration, there was a marked reduction in [O(2)Hb] and CBV which reached their worst level 40 min after initiation of CPB (from -3.03+/-5.1 to -9.25+/-7.20 micromol/l for [O(2)Hb], and a 24% reduction for CBV (both P<0.0001). The deterioration in [O(2)Hb] was recovered by the end of surgery, while the changes in CBV persisted. No significant changes occurred with respect to [HHb], [Cyt-Ox], and TOI. Conventional CABG is responsible for deterioration in [O(2)Hb], and CBV, which peak at 40-60 min following initiation of CPB. The changes in [O(2)Hb] are reversible whereas the reduction of CBV persists to the end of the surgery. This suggests a transient impairment in the autoregulatory mechanisms controlling cerebral blood flow following discontinuation of cardiopulmonary bypass.

Cerebral cortical oxygenation: a pilot study.

Cerebral hypoxia (cerebral cortical oxygenation [Pbro2] < 20 mm Hg) monitored by direct measurement has been shown in animal and small clinical studies to be associated with poor outcome. We present our preliminary results observing Pbro2 in patients with traumatic brain injury (TBI). A prospective observational cohort study was performed. Institutional review board approval was obtained. All patients with TBI who required measurement of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbro2 because of a Glasgow Coma Scale score < 8 were enrolled. Data sets (ICP, CPP, Pbro2, positive end-expiratory pressure (PEEP), Pao2, and Paco2) were recorded during routine manipulation. Episodes of cerebral hypoxia were compared with episodes without. Results are displayed as mean +/- SEM; t test, chi2, and Fisher's exact test were used to answer questions of interest. One hundred eighty-one data sets were abstracted from 20 patients. Thirty-five episodes of regional cerebral hypoxia were identified in 14 patients. Compared with episodes of acceptable cerebral oxygenation, episodes of cerebral hypoxia were noted to be associated with a significantly lower mean Pao2 (144 +/- 14 vs. 165 +/- 8; p < 0.01) and higher mean PEEP (8.8 +/- 0.7 vs. 7.1 +/- 0.3; p < 0.01). Mean ICP and CPP measurements were similar between groups. In a univariate analysis, cerebral hypoxic episodes were associated with Pao2 < or = 100 mm Hg (p < 0.01) and PEEP > 5 cm H2O (p < 0.01), but not ICP > 20 mm Hg, CPP < or = 65 mm Hg, or Pac2 < or = 35 mm Hg. Cerebral oxymetry is confirmed safe in the patient with multiple injuries with TBI. Occult cerebral hypoxia is present in the traumatic brain injured patient despite normal traditional measurements of cerebral perfusion. Further research is necessary to determine whether management protocols aimed at the prevention of cerebral cortical hypoxia will affect outcome.

Cerebral cortical oxygenation changes during OPCAB surgery

Background We investigated the changes occurring in cerebral cortical oxygenation during off-pump coronary artery bypass (OPCAB) surgery using near infrared spectroscopy (NIRS). Methods Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated hemoglobin [HHb], oxygenated hemoglobin [O 2Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue hemoglobin index (THI). Measurements were performed in 23 consecutive patients during grafting of: left anterior descending (LAD setup 1; n = 23), posterior descending (PDA setup 2; n = 17), and Circumflex (Cx setup 3; n = 19) coronary arteries. Measurements were performed before any surgical manipulation (baseline), following positioning of the pressure stabilizer during construction of the distal anastomosis and 2 minutes after the completion of each distal anastomosis with the heart returned to its natural position. Results There were no in-hospital deaths, neurologic deficits, or myocardial infarcts. Compared to baseline, during LAD grafting there was a marked reduction in [O 2Hb] [−1.08 (−1.77 to −0.39), mean difference (95% CI) ( p < 0.0008)], without a significant change in [HHb]. There was also a 4% reduction in cerebral saturation and a 3% fall in CBV (both p < 0.05). Setup 2 (PDA) was associated with a marked decrease of [O 2Hb] [−1.92 (−2.95 to −0.88) mean difference (95% CI) ( p < 0.0025)], which was accompanied by an increase in [HHb] [1.89 (1.00 to 2.77) mean difference (95% CI) ( p < 0.0025)], and a 4% reduction in cerebral saturation ( p < 0.0008). Grafting of the Cx was associated with a marked increase in [HHb] [2.85 (1.46 to 4.2) mean difference (95% CI) ( p < 0.0025)], with no changes in [O 2Hb], a 6% reduction in cerebral saturation, and a 12% increase in CBV (both p < 0.05). In all 3 settings, however, the changes were not associated with a modification in the redox state of [Cyt-Ox]. On returning to baseline condition, the changes in [O 2Hb] and TOI observed in setup 1 persisted, and a significant reduction was observed in the redox state of the [Cyt-Ox] when compared with baseline [−0.08 (−0.14 to −0.02) mean difference (95% CI) ( p < 0.002)]. For setups 2 and 3 there was recovery of the cerebral cortical oxygenation. Conclusions Grafting of the LAD on the beating heart is responsible for changes in cerebral cortical oxygenation which persist early after returning the heart to its natural position. Grafting of the Cx and PDA result in transient reversible changes. Trendelenburg positioning and right lateral tilting of the operating table during grafting of lateral and posterior walls might have a protective role in preventing cerebral cortical ischemia. Further studies are needed to assess the clinical importance of these observations.

Norepinephrine in the Rat Cortex before and after Occlusion of Chronic Arteriovenous Fistulae: A Microdialysis Study in an Animal Model of Cerebral Arteriovenous Malformations

In an animal model, we tested the hypothesis that intracerebral, extracellular norepinephrine (NE) influences cerebral blood flow (CBF) in the presence of cerebral arteriovenous malformations (AVMs). A microdialysis (MD) probe was implanted into the cortices of Sprague-Dawley rats 3 months after the creation of extracranial arteriovenous fistulae (AVFs; n = 19), carotid ligation (n = 10), and cervical vessel preparation (sham operations; n = 8). Ipsilateral regional cortical oxygen saturation (microspectrophotometry) and regional cerebral blood flow (laser Doppler flowmetry) were scanned with simultaneous MD sampling for NE (high-performance liquid chromatography). Local CBF and cortical capillary oxygen saturation (SO2) were recorded continuously with serial MD sampling after fistula occlusion for 100 minutes. The scanning protocol was repeated after 120 minutes. Values were compared by analysis of variance and Duncan's test (P < 0.05; values expressed as mean +/- standard deviation). NE was highest in sham-operated animals and lowest after carotid ligation as compared with before and after the creation of the AVFs (sham operations, 5.9 +/- 2.3 nmol/L; common carotid artery ligation, 2.4 +/- 1 nmol/L; before creation of AVF, 4.1 +/- 1.9 nmol/L; after creation of AVF, 4.1 +/- 2.3 nmol/L). Regional cortical oxygen saturation differed significantly between all groups; regional cerebral blood flow was lower only in sham-operated animals (sham operations, 210 +/- 75 laser Doppler units [LDU], 71 +/- 13% SO2; common carotid artery ligation, 250 +/- 82 LDU, 62 +/- 19% SO2; before creation of AVF, 249 +/- 96 LDU, 65 +/- 14% SO2; after creation of AVF, 256 +/- 82 LDU, 74 +/- 10% SO2). After fistula occlusion, a sustained CBF increase for 100 minutes up to 40% above baseline (i.e., regional cerebral blood flow and regional cortical oxygen saturation before occlusion) was observed. SO2 increased to 16% after 120 minutes. Peaks of NE concentrations occurred 40 minutes and 100 minutes after fistula occlusion. The model seems to be valid for the simulation of events that occur before and after the obliteration of human cerebral AVMs in most cases, but not in those prone to hyperperfusion syndromes. The results provide evidence that cerebral sympathetic nervous system activity can be monitored by in vivo MD and that NE may play a role in CBF control before and after the obliteration of AVFs.

Simultaneous measurements of cerebral oxygenation changes during brain activation by near‐infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.

Functional cerebral hyperemia is unaffected by isovolemic hemodilution.

The cerebral hyperemic effect of hemodilution is well known; however, its mechanism and potential modifying effect on the functional hyperemic response to neuronal activation are unclear. The authors investigated the effects of isovolemic hemodilution on vibrissal stimulation-induced changes in cerebrocortical laser Doppler flow and tissue oxygen tension in the rat. The hyperemic response to whisker stimulation was assessed in the whisker barrel cortex of 12 rats anesthetized with chloralose-urethane before and after hemodilution. Graded, isovolemic hemodilution was performed by three repeated withdrawals of 3 ml blood with replacement of equal volume of 5% serum albumin. Measured systemic hematocrit values were 39.3 +/- 1.3% (control), 29.5 +/- 1.0%, 22.3 +/- 1.5%, and 17.0 +/- 1.6% (after the three hemodilution steps). Arterial blood pressure was maintained at control levels with an infusion of methoxamine. Unilateral whisker stimulation was performed with a mechanical actuator at 8 Hz, and 10 cycles of 10 s on-30 s off periods. In six control animals, shed blood was immediately reinfused, resulting in no change in hematocrit, and whisker stimulation was performed using the same timeline as in the other animals. In six additional experiments, resting cerebral cortical oxygen tension was measured using the phosphorescence quenching technique following the same hemodilution protocol. Graded hemodilution increased baseline laser Doppler flow by 5.5 +/- 0.9%, 13 +/- 1.6%, and 23.7 +/- 2.2%. Vibrissal stimulation transiently increased laser Doppler flow by 17.0 +/- 2.0%. The hyperemic response was unchanged after hemodilution and was identical to that seen in the control group in all conditions. Tissue oxygen tension increased slightly but significantly with hemodilution at a rate of 1.4 mmHg per 10% hematocrit change (r = 0.83). Mean arterial pressure, arterial oxygen tension, carbon dioxide tension, and pH were within normal limits in each experimental group and were not different from control during hemodilution. The results suggest that an increase in baseline flow during hemodilution maintains cortical oxygen supply and consequently preserves the normal functional hyperemic response.

Neuroprotection of S(+) ketamine isomer in global forebrain ischemia

The non-competitive N-methyl- d-aspartate (NMDA) receptor antagonist ketamine can block the action of excitotoxic amino acids in the central nervous system. S(+) ketamine has a 2–3 times higher anesthetic potency compared with the ketamine-racemate and also shows a higher neuroprotective efficacy in vitro. To determine the neuroprotective activity of S(+) ketamine compared with its R(−) stereoisomer in vivo, we examined the functional and neurohistological outcome in rats treated 15 min after global forebrain ischemia with S(+) ketamine in different dosages compared with R(−) ketamine. Influence of the treatment on regional cerebral blood flow (rCBF) and cortical oxygen saturation (HbO 2) was monitored over 1 h after the ischemia using laser doppler flowmetry and microphotospectrometry respectively. Sixty and ninety mg/kg of S(+) ketamine but not R(−) ketamine significantly reduced neuronal cell loss in the cortex compared with the saline treated group. No significant neuroprotection was observed in the hippocampus. Although no significant change in rCBF was found, S(+) ketamine restored the cortical HbO 2 to preischemic values. These results indicate that S(+) ketamine in higher dosages can reduce neuronal damage in the cortex after cerebral ischemia, possibly by improving the ratio of oxygen supply to consumption in the postischemic tissue.

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older.

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day-to-day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70-84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6.7 +/- 15.4 mmHg (P<0.05, mean +/- SD) and 8.2 +/- 6.4 mmHg (P<0.01), respectively, whereas HR increased by 9.5 +/- 5.0 bpm (P<0.01) and SV decreased by -8.3 +/- 7.4 ml (P<0.01) during standing on the first occasion. [O2Hb] decreased by -3.9 +/- 2.9 micromol l-1 (P<0.01), while [HHb] increased by 1.8 +/- 2.2 micromol l-1 (P<0.01). Group-averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group-averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day-to-day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.

Effect of AMPA on cerebral cortical oxygen balance of ischemic rat brain.

We tested the hypothesis that the excitatory neurotransmitter receptor agonist, alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), would worsen cerebral cortical oxygen supply/consumption balance during focal ischemia. In this study, we compared regional cerebral blood flow, arterial and venous O2 saturation, O2 extraction and oxygen consumption of ischemic and AMPA treated ischemic and control regions of rat brain. Ischemia was induced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthetized Wistar rats. Twenty minutes after MCA occlusion, 10(-5) M AMPA was applied to the ischemic cortex (IC) for a period of 40 min; the fluid was changed every 10 min. After 1 hr of ischemia, animals were sacrificed and regional cerebral blood flow (rCBF) was determined using the C14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. In control, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 46 +/- 20 vs. 81 +/- 39 ml/min/100g, O2 consumption: 2.8 +/- 1.4 vs. 3.6 +/- 1.4 ml O2/min/100g). 10(-5) M AMPA did not significantly alter regional cerebral blood flow and oxygen consumption of the IC, but did decrease the average venous O2 saturation of the IC from 50.2 +/- 3.9% to 46.7 +/- 1.6%. AMPA also significantly increased the frequency of small veins with less than 45% O2 saturation in the IC (8 out of 56 veins in IC vs. 18 out of 56 veins in AMPA treated IC). Thus, topical application of 10(-5) M AMPA to the ischemic area worsens cerebral O2 balance and suggests that excitatory amino acids contribute to the degree of cerebral ischemia.

The effects of induced apneic episodes on cerebral cortical oxygenation in newborn piglets

The effect of different inspiratory oxygen levels (FiO 2) on cortical oxygenation ( pO 2) during and after recovery from apnea, was investigated in 18 anesthetized, paralyzed, and mechanically ventilated newborn piglets. Heart rate (HR) and mean arterial blood pressure (MABP) were continuously monitored as the piglets were subjected to repeated episodes of apnea initiated by disconnecting the ventilator and terminated when HR decreased to less than 80 beats/min by reconnecting the ventilator. A closed cranial window was placed over the parietal cortex of the animals and cortical pO 2 was measured optically by phosphorescence quenching. Apneic episodes induced in animals ventilated with 15%, 22% and 40% oxygen had mean duration's of apnea (time before HR decreased to less than 80 beats/min) of 80, 128 and 134 s, respectively. By the end of the apnea the MABP decreased to 82%, 64%, and 54% of control, respectively. The cortical pO 2 decreased from control values of 24.1, 32.3 and 38.3 Torr at 15%, 22% and 40% oxygen, respectively, to 1.7 to 3.2 Torr at the end of the apneic episode. The duration of apnea necessary for the cortical pO 2 to drop below 20.3 Torr was 18, 44 and 81 s at 15%, 22% and 40% oxygen, respectively. There was an inverse correlation between the rate of decline of cortical pO 2 and baseline FiO 2 levels. With reventilation, the cortical pO 2 reached maximal values of 42.8, 51.9 and 57.2 Torr at 15%, 22%, and 40% oxygen, respectively, before returning to the pre-apnea values. The present results show that apnea of less than 30 s duration at an FiO 2 of 22% do not result in significant cortical hypoxia in hemodynamically stable piglets. Increasing the FiO 2 to above 22% may possibly increase the rate of recovery of tissue oxygenation but it also may facilitate post-hypoxic cortical hyperoxia, a factor that may predispose the immature brain to free radical injury.