Measurement Of Local Cerebral Blood Flow Research Articles

Discordant results from global versus local cerebral blood flow measurements in response to rhythmic handgrip exercise

BackgroundThe cerebral blood flow (CBF) response to exercise can be measured in a larger vessel such as the middle cerebral artery (MCA; e.g. by transcranial Doppler; TCD) and at tissue level by e.g. arterial spin labeling MRI (ASL). The reported changes in total CBF between artery flow and tissue flow approaches are, however, inconsistent [1]. The aim of the current study was to evaluate TCD and ASL measurements in response to the same protocol of rhythmic handgrip exercise in the same subjects, to determine into what degree large vessel blood flow measurements conform to local perfusion measures. As a second aim, the assumption of constant vessel cross‐sectional area (CSA) during handgrip exercise was assessed by high resolution MRI.MethodsOn 2 different sessions separated by 1 week, heart rate (HR) and end‐tidal CO2 (PETCO2) were recorded in 11 subjects (5 female) during rhythmic handgrip. Three 5‐minutes runs of rhythmic handgripping at 60% of maximal voluntary contraction were alternated with 5 minutes of rest. During the first session regional CBF velocity (CBFv) was measured in the MCA by TCD and during the second session tissue perfusion (CBFt) was determined with ASL (3T Philips MRI, 17 slices). The CSA of the contralateral MCA was assessed with the same exercise protocol in a separate cohort of subjects (n=11, 5 female) using direct 7 Tesla MRI observations (following [2]).ResultsIn response to rhythmic handgrip exercise, an increase in regional CBFv (5±6%, p<0.01) and motor area CBFt (10±6%, p<0.01) was demonstrated, while whole brain gray matter CBFt did not change (1±8% p=0.75). During both sessions, the increase in HR was similar (11±6% vs. 15±8%, p=0.81) whereas PETCO2 did not change. No differences in absolute resting values for HR (p=0.09) and mean arterial pressure (p=0.27) were observed. Resting PetCO2 was slightly higher (2.3mmHg, p<0.01) during the MRI session.High resolution MR imaging demonstrated a decrease in the MCA CSA (−4.0±0.6%; p<0.001) in response to handgrip, together with an increase in HR (11±1%, p<0.001) whereas PETCO2 remained constant (p=0.72).DiscussionThe 10% CBFt increase as detected with ASL was restricted to the motor cortex, which represents only 2% of the total MCA flow‐territorial volume. When extrapolated to the total flow‐change within the MCA flow territory, this would represent only a 0.2% increase, as also confirmed by the non‐significant change of whole brain gray matter flow (1±8%). However, our TCD measurements indicated a 5% CBFv increase of the entire flow territory. These measures of CBF were therefore inconsistent and differed by a factor 25. The present findings could be explained by the observed vasoconstriction of the MCA, but also other physiological phenomena, such as arteriovenous shunts, or a breakdown of other assumptions of the applied technologies, such as flow profile changes might be involved. A limitation is that the two sub‐studies were performed in different subjects.ConclusionThis study demonstrates discordant results from global (TCD) and local (ASL) cerebral blood flow measurements in response to rhythmic handgrip exercise. The observed reduction in MCA CSA implicates that the blood flow velocity changes measured by TCD overestimate the effects of mild exercise on CBF. Further pinpointing the nature of these discordant results will help interpretation of TCD and ASL studies concerning regulation of CBF.Support or Funding InformationThis study is supported by the Rembrandt Institute of Cardiovascular Science

Preventing flow-metabolism uncoupling acutely reduces axonal injury after traumatic brain injury.

We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via ¹⁸F-fluorodeoxyglucose and ¹⁴C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of β-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3-24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons.

Effect of stage 2 kindling on local cerebral blood flow rates in rats with genetic absence epilepsy

Genetic absence epilepsy rats from Strasbourg (GAERS) are resistant to the progression of kindling seizures. We studied local cerebral blood flow (LCBF) changes in brain regions involved in seizures in both GAERS and nonepileptic rats (NEC) to map the differences that may be related to the resistance to kindling. Electrodes were implanted in the amygdala of adult NEC and GAERS male rats, which were stimulated to reach stage 2. Quantitative autoradiographic measurements of LCBF were performed by the [(14)C]-iodoantipyrine ([(14)C]IAP) autoradiographic technique allowing the precise mapping of regional perfusion changes. LCBF rates were measured bilaterally in 43 brain regions. The tracer infusion lasted for 60 s and started at 15 s before seizure induction. Rates of LCBF increased in stimulated GAERS and NEC groups compared to nonstimulated controls. The LCBF increase in stimulated GAERS was larger and more widespread than that observed in stimulated NEC. The LCBF increase in the somatosensory cortex, ventrobasal and anterior thalamic nuclei, hypothalamus, subthalamic nucleus, piriform, entorhinal and perirhinal cortex, amygdala, CA2 region of hippocampus, and substantia nigra was statistically significantly larger in stimulated GAERS compared to stimulated NEC rats. The results show that more brain regions are activated by kindling stimulation in GAERS. This widespread activation in GAERS involves the somatosensory cortex and thalamus, which are both known to be involved in the expression of absence seizures as well as numerous limbic regions thought not to play a role in the expression of absence seizures, suggesting an interaction between corticothalamocortical and limbic circuitries.

Local Cerebral Blood Flow is Preserved in Sepsis

Sepsis is often complicated by encephalopathy, neuroendocrine dysfunction and cardiovascular autonomic failure. The cause of septic brain dysfunction is not fully understood. The aim of the present study is to explore whether septic brain dysfunction in a common septic model in the rat correlates with abnormalities either of local cerebral blood flow (LCBF) of defined brain areas or of whole brain blood flow (CBF). 45 male Wistar rats (320+/-13 g) were randomly assigned to a sepsis group (31 rats, cecal ligature and puncture, CLP) or a control group (14 rats, sham operation). Of these 45 rats, 16 rats were used for blood analysis; the remaining 29 rats were used for CBF/LCBF measurements. LCBF measurements were performed 24h after initial surgery using quantitative autoradiography with 4-iodo[N-methyl-(14)C]antipyrine, which allows to analyze CBF on a regional/local and global basis. In 42 different brain regions bilateral optical density measurements were performed. Septic rats (vs. control) presented tachycardia (507+/-37 vs. 452+/-44 min(-1), P<0.05), leukocytopenia (2.96+/-2.37 vs. 8.83+/-2.9710(9) x L(-1), P<0.05), hypocapnia (29.3+/-4.6 vs. 36.4+/-3.9 mmHg, P<0.05), and higher serum lactate concentrations (5.7+/-3.9 vs. 2.2+/-2.0 mmol x L(-1), P<0.05). LCBF of all 42 areas, as well as, CBF (116+/-59 vs. 115+/-52 m x 100 g(-1)min(-1), n.s.) did not differ. The results showed that severe sepsis (mortality rate of 43 %) did not induce alterations in mean CBF and LCBF. It is concluded that brain dysfunction is not reflected in changes of CBF during severe sepsis.

Uncoupling of cerebral blood flow and metabolism after cerebral contusion in the rat.

Positron emission tomography scans of patients with head injuries often show discrete areas of increased 18F-fluorodeoxyglucose uptake ("hot spots") when performed hours to days after the initial ictus. Using quantitative autoradiographic methods, the authors have investigated whether cerebral blood flow and glucose metabolism are uncoupled 2 hours after controlled head injury in an animal model, and whether any "hot spots" are accompanied by changes in cerebral glucose concentration. Experiments were performed on 18 anesthetized, ventilated (1.5% halothane in 2:1 nitrous oxide:oxygen) Sprague-Dawley rats weighing 300 to 330 g. A burr hole was made over the left parietal cortex, and all animals received a piston impact on the intact dura (2 mm in diameter, 2.0 m/sec, 2 mm in depth). All animals remained anesthetized and ventilated for a further 2 hours, after which quantitative autoradiography was used to determine either (1) local cerebral blood flow (LCBF) using 14C-iodoantipyrine, (2) local cerebral glucose utilization (LCGU) using 14C-deoxyglucose, or (3) local cerebral glucose content (LCGC) using 14C-methylglucose. Local CBF, LCGU, and LCGC were measured in five regions adjacent to the contusion, and values then were normalized on the contralateral cortex. Normalized LCBF, LCGU, or LCGC varied in parallel in ipsilateral cortex (no change) and in the ischemic core of the contusion (reduced). However, there were marked changes in the patterns observed in the boundary zone (within 1 mm of the contusion). In all six rats used for LCGU measurement, there were discrete areas of high metabolism, whereas in all six rats used for LCBF measurement, flow was universally depressed in the boundary zone. Of the six rats used for LCGC determination, there was a discrete area of high signal in only one. The authors conclude that there are discrete areas of uncoupling of cerebral blood flow and metabolism after head injury within 2 hours of cerebral contusion in the rat that cannot be explained by changes in cerebral glucose content in the majority of animals.

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats.

The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.

Quantitative Measurement of Local Cerebral Blood Flow in the Anesthetized Mouse Using Intraperitoneal [14C]Iodoantipyrine Injection and Final Arterial Heart Blood Sampling

Autoradiographic measurement of local cerebral blood flow (CBF) with [14C]iodoantipyrine (IAP) is limited in mice by the difficulty in cannulating vessels and the blood loss for repeated blood sampling. The authors modified and validated the method to measure local CBF with [14C]IAP in mice by combining intraperitoneal tracer application with a single blood sampling from the heart at the end of the experiment. Experiments were carried out in male SV129 mice under halothane anesthesia. After intraperitoneal administration of 15 microCi [14C]IAP, arterial blood samples were collected repeatedly and anesthetized animals were immersed in liquid nitrogen. In addition, frozen blood from the heart was sampled to obtain the final blood [14C]radioactivity. Correlation analysis between the sampling time and [14C]radioactivity of the arterial blood revealed a highly significant linear relationship (P < 0.001, r = 0.978) and a lag time of the [14C]tracer in arterial blood of 3.3 +/- 0.6 seconds. [14C]radioactivity of the final arterial blood sample (444 +/- 264 nCi/mL) was almost equal to that of the heart blood (454 +/- 242 nCi/mL), and the absolute difference in each animal was 3.3 +/- 4.2% (mean +/- SD). The convolution integrals for the CBF calculation were determined either by integrating the radioactivity of individual arterial blood samples or by assuming a linear rise from [14C]tracer lag time after intraperitoneal [14C]IAP injection to the value measured in the blood sample from the frozen heart. Regional flow values calculated by the two methods differed by less than 11% (not significant). This method allows the quantitative measurement of local CBF in anesthetized mice without any vessel catheterization and will make mutant mice a more powerful tool to elucidate the molecular mechanisms of brain injuries by combining flow studies with molecular-biological methods.

Laser Doppler scanning: how many measurements are required to assess regional cerebral blood flow?

This study was initiated to determine the optimal number of measuring sites necessary to estimate regional cerebral blood flow (CBF) under pathophysiological conditions. 25 rats were exposed to 15 minutes of global cerebral ischemia. Local CBF was sequentially measured by laser Doppler (LD) at 32 locations during baseline conditions, ischemia and reperfusion using a computer-controlled scanning technique. A simulation study was performed based on 800 local measurements at each time point: random samples (size 1-100) were repeatedly drawn to estimate the variability of median flow. Accuracy was defined as probability that the simulated median differed less than +/- 5 LD-units from the true median of the 800 data. Above a single location, CBF was measured with an accuracy of 21.6 +/- 0.4% (baseline conditions, n = 100 simulations, mean +/- SEM), 85.8 +/- 0.4% (ischemia) and 11.1 +/- 0.3% (30th min. reperfusion). Accuracy increases to 75.2 +/- 0.5% (baseline conditions), 100 +/- 0% (ischemia) and 41.8 +/- 0.6% (30th min. reperfusion) if 24 locations are scanned. Scanning, therefore, improves accuracy and reduces variability of CBF measurements. With enough local CBF measurements laser Doppler assessment of regional CBF is possible. Single location CBF assessment is sufficiently accurate only during ischemia. During reperfusion, when accuracy is half reduced compared to baseline conditions, larger sample sizes are required.

Measurement of Local Cerebral Blood Flow By Magnetic Resonance Imaging: In Vivo Autoradiographic Strategy Using 17O-Labeled Water

Local cerebral blood flow (LCBF) was measured in cats by magnetic resonance imaging (MRI), using 17O-labeled water (H 2 17O) as a tracer. Cat brain images were obtained using a 256 × 240 matrix fast spin-echo sequence with a total acquisition time of 124 seconds per image. Intravenous injection of H 2 17O and sampling of arterial blood were simultaneously performed during the MRI scan. Injection of H 2 17O over 40 seconds caused a transient decrease in brain signal intensity, from which the changes in H 2 17O concentration of brain tissue were calculated. The concentration of H 2 17O in arterial blood was measured directly by 17O nuclear magnetic resonance (NMR) spectroscopy, and used as an input function for the calculation of LCBF. LCBF was successfully determined using an in vivo autoradiographic strategy in a total of three cats. In one, LCBF measurements were also performed under hypercapnic conditions, and LCBF maps of the cat brain during normocapnia and hypercapnia were constructed. These LCBF maps reflected well the changes in LCBF induced by hypercapnia, which indicated the validity of the used method.

The relationship of blood velocity as measured by transcranial doppler ultrasonography to cerebral blood flow as determined by stable xenon computed tomographic studies after aneurysmal subarachnoid hemorrhage.

Transcranial doppler (TCD) ultrasonography is often used to guide the management of patients with subarachnoid hemorrhage (SAH). However, the correlation between increased blood velocity as measured by TCD ultrasonography and angiographic vasospasm was established before the routine use of hypervolemia/hemodilution and administration of nimodipine and did not address blood flow. The relationship of blood velocity as measured by TCD ultrasonography and local cerebral blood flow (LCBF) in SAH managed with these modalities is unknown. Patients presenting with aneurysmal SAH between January 1992 and September 1993 who underwent TCD ultrasonography and xenon computed tomographic (Xe/CT) LCBF studies within 12 hours were retrospectively studied. Fifty patients underwent a total of 94 paired studies, encompassing 709 vascular territories. All were treated with nimodipine and hypervolemia/hemodilution. Hematocrit, blood pressure, and partial carbon dioxide pressure were similar at the time of TCD ultrasonography and Xe/CT measurement of LCBF. When LCBF in the middle cerebral artery (MCA) was < or = 31 ml/100 g/min, the corresponding peak systolic velocity measured by TCD ultrasonography was 119 cm/s, whereas those > 31 ml/100 g/min had a velocity of 169 cm/s (P = 0.006). High LCBF was associated with high velocity in all vascular territories, reaching significance in all but the internal carotid artery. At the time of each study, 41 neurological examinations were focal and 53 were nonfocal. The Xe/CT measurement of LCBF in the MCA contralateral to a deficit was significantly less than in territories without corresponding clinical deficits (P = 0.01), whereas peak systolic velocities in the MCA were not significantly different (P = 0.71). Territories with increases in blood velocity in the MCA of > 50 cm/s/24 h did not have statistically different LCBF (P = 0.183). Our results suggest that increased blood velocity revealed by TCD ultrasonography correlates with increased LCBF and not with ischemia. No difference in LCBF was found in territories with and without rapid increases in blood velocity in the MCA. Furthermore, although focal neurological deficits corresponded with decreased contralateral LCBF in the MCA, increased velocity did not correlate with neurological findings. Therapeutic decisions based solely on blood velocity revealed by TCD ultrasonography might be inappropriate and potentially harmful. Xe/CT studies of LCBF are useful in guiding the management of SAH.

Cerebrovascular responsiveness to NG-nitro-L-arginine methyl ester in spontaneously diabetic rats.

1. There is evidence that endothelial dysfunction is associated with diabetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in spontaneously diabetic insulin-dependent BioBred (BB) rats. 2. Diabetic rats, and non-diabetic controls, were treated with L-NAME (30 mg kg-1, i.v.) or saline, 20 min prior to the measurement of LCBF by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. There were no significant differences in physiological parameters (blood pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response to L-NAME between diabetic and non-diabetic rats. 4. In diabetic rats, a global reduction in basal LCBF was observed, although significant reductions (between -20 and -30%) were found in only 5 (mainly subcortical) out of the 13 brain regions measured. Following L-NAME injection, significant reductions in LCBF (between -20 and -40%) were found in the non-diabetic animals. In diabetic animals treated with L-NAME, a significant reduction in LCBF was measured only in the hypothalamus (-33%). 5. The cerebrovascular response to acute L-NAME is attenuated in spontaneously diabetic insulin-dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be associated with diabetes mellitus and it is possible that a loss of NO-induced dilator tone, amongst other factors, may underlie the observed reductions of basal LCBF in these animals.

In vivo production of nitric oxide correlates with NMDA-induced cerebral hyperemia in newborn sheep

Stimulation of N-methyl-D-aspartate (NMDA) receptors in brain increases nitric oxide production in vitro. We tested the hypothesis that nitric oxide participates in the increase in local cerebral blood flow (CBF) caused by infusion of NMDA in anesthetized newborn sheep. We used the combined hydrogen clearance and microdialysis technique for simultaneous measurement of local CBF, infusion of drugs, and measurement of interstitial levels of L-[14C]citrulline in the parietal cortex. Release of L-[14C]citrulline into the dialysate during continuous infusion of L-[14C]arginine was used as a marker of nitric oxide production in vivo. Citrulline recovery and CBF were measured hourly during a 4-h infusion of cerebrospinal fluid containing either 1) no additional drugs, 2) 1 mM NMDA, 3) 1 mM NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), 4) 1 mM NMDA + 1 mM L-NAME, 5) 0.1 mM 2-chloroadenosine (adenosine receptor agonist), or 6) 0.1 mM 2-chloroadenosine + 1 mM L-NAME. At 240 min of perfusion, CBF (ml.min-1.100 g-1; means +/- SE) was as follows: control 52 +/- 3, NMDA 116 +/- 11, L-NAME 32 +/- 5, NMDA+L-NAME 40 +/- 4,2-chloroadenosine 201 +/- 63, and 2-chloroadenosine+L-NAME 129 +/- 18. Citrulline recovery (fmol/min) at 240 min of perfusion was as follows: control 38 +/- 12, NMDA 149 +/- 21, L-NAME 9 +/- 1, NMDA+L-NAME 39 +/- 5, 2-chloroadenosine 13 +/- 5, and 2-chloroadenosine+L-NAME 17 +/- 1.(ABSTRACT TRUNCATED AT 250 WORDS)

MAC of xenon and halothane in rhesus monkeys.

Local cerebral blood flow (LCBF) maps produced by 33% xenon-enhanced computed tomographic scanning (Xe/CT LCBF) are useful in the clinical diagnosis and management of patients with cerebrovascular disorders. However, observations in humans that 25-35% xenon (Xe) inhalation increases cerebral blood flow (CBF) have raised concerns that Xe/CT LCBF measurements may be inaccurate and that Xe inhalation may be hazardous in patients with decreased intracranial compliance. In contrast, 33% Xe does not increase CBF in rhesus monkeys. To determine whether this interspecies difference in the effect of Xe on CBF correlates with an interspecies difference in the anesthetic potency of Xe, we measured the minimum alveolar concentration (MAC) of Xe preventing movement to a tail-clamp stimulus in rhesus monkeys. Using a standard protocol for the determination of MAC in animals, we first measured the MAC of halothane (n = 5), and then used a combination of halothane and Xe to measure the MAC of Xe (n = 7). The halothane MAC was 0.99 +/- 0.12% (M +/- SD), and the Xe MAC was 98 +/- 15%. These results suggest that the MAC of Xe in rhesus monkeys is higher than the reported human Xe MAC value of 71%. Thus the absence of an effect of 33% Xe on CBF in the rhesus monkey may be related to its lower anesthetic potency.

Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats.

There have been few investigations of brain edema formation after intracerebral hemorrhage (ICH), despite the fact that mass effect and edema are important clinical complications. The present study was designed to investigate the time course for the formation and resolution of brain edema and to determine how changes in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability are temporally related to edema formation following ICH. Anesthetized adult rats received a sterile injection of 100 microliters of autologous blood into the caudate nucleus. Water and ion contents were measured immediately, at 4 and 12 hours, and daily to Day 7 (10 time points, six rats at each time) after experimental ICH. The water content of the ipsilateral basal ganglia increased progressively (p < 0.002) over the first 24 hours, then remained constant until after Day 5, when the edema began to resolve. Edema was most severe in the tissue immediately surrounding the hemorrhage; however, it was also present in the ipsilateral cortex, the contralateral cortex, and the basal ganglia. Measurements of local CBF (using [14C]-iodoantipyrine) and BBB permeability (using [3H]-alpha-aminoisobutyric acid) were obtained in separate groups of six to eight rats at various time intervals between 1 and 48 hours after ICH. Cerebral blood flow was reduced to 50% of control at 1 hour, returned to control values by 4 hours, but then decreased to less than 50% of control between 24 and 48 hours after ICH. The BBB permeability increased significantly prior to the occurrence of significant edema in the tissue surrounding the clot. However, BBB permeability in the more distant structures remained normal despite the development of edema. These results demonstrate a time course for the formation and resolution of brain edema following ICH similar to that observed during focal ischemia. Brain edema forms in the immediate vicinity of the clot as a result of both BBB disruption and the local generation of osmotically active substances and then spreads to adjacent structures. While local ischemia, due to the mass effect of the hemorrhage, may play a role in producing cytotoxic and vasogenic edema, the release of toxic substances from the clot should also be considered. Since edema is nearly maximal by 24 hours after ICH, therapy directed at reducing edema formation must be instituted within the 1st day.

Acute cerebral blood flow response to dopamine-induced hypertension after subarachnoid hemorrhage.

The effects of dopamine-induced hypertension on local cerebral blood flow (CBF) were investigated in 13 patients suspected of suffering clinical vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The CBF was measured in multiple vascular territories using xenon-enhanced computerized tomography (CT) with and without dopamine-induced hypertension. A territorial local CBF of 25 ml/100 gm/min or less was used to define ischemia and was identified in nine of the 13 patients. Raising mean arterial blood pressure from 90 +/- 11 mm Hg to 111 +/- 13 mm Hg (p < 0.05) via dopamine administration increased territorial local CBF above the ischemic range in more than 90% of the uninfarcted territories identified on CT while decreasing local CBF in one-third of the nonischemic territories. Overall, the change in local CBF after dopamine-induced hypertension was correlated with resting local CBF at normotension and was unrelated to the change in blood pressure. Of the 13 patients initially suspected of suffering clinical vasospasm, only 54% had identifiable reversible ischemia. The authors conclude that dopamine-induced hypertension is associated with an increase in flow in patients with ischemia after SAH. However, flow changes associated with dopamine-induced hypertension may not be entirely dependent on changes in systemic blood pressure. The direct cerebrovascular effects of dopamine may have important, yet unpredictable, effects on CBF under clinical pathological conditions. Because there is a potential risk of dopamine-induced ischemia, treatment may be best guided by local CBF measurements.

Local cerebral blood flow measured by stable xenon CT during fentanyl-diazepam anesthesia.

We assessed the local cerebral blood flow (LCBF) in 40 patients under fentanyl-diazepam anesthesia. The measurement of LCBF was made using 50%-70% stable xenon with 20 min of inhalation interval and a shuttle method for computed tomography imaging. All patients were anesthetized with 5.95±1.76 μg·kg-1 fentanyl and 0.22±0.07 mg·kg-1 diazepam under mechanical ventilation during CBF measurement. The values and distribution of LCBF on non-affected hemisphere appeared to be unaltered by fentanyldiazepam anesthesia. We also assessed the cerebral carbon dioxide reactivity in 6 patients. The cerebral carbon dioxide reactivity, expressed as percentage change in LCBF per unit change in arterial carbon dioxide partial pressure, was 5.39±1.07, and there were no significant differences of reactivity among regions studied. In conclusion, we showed reference values of LCBF and carbon dioxide reactivity, measured by stable xenon-enhanced computed tomography, in patients under fentanyl-diazepam anesthesia. Carbon dioxide reactivity was preserved in all regions including gray matter, white matter, and basal ganglia.

Regional cerebral blood flow response to acute hypoxia changes with postnatal age in the rat

The quantitative autoradiographic [ 14C]iodoantipyrine technique was applied to measure the effects of an acute hypoxic exposure on rates of local cerebral blood flow (LCBF) in the 10 (P10)-, 14 (P14)- and 21 (P21)-day-old rat. The animals were exposed to hypoxic (7% O 2/93% N 2) or control gas mixtures (21% O 2/79% N 2) for 40 min before the initiation of the 1-min LCBF measurement. At P10, hypoxia induced a 142–415% increase in LCBF over in LCBF were noticed in posterior midbrain and brainstem regions. These increases are in good accordance with hypoxia-induced increases in LCBF recorded during acute hypoxia exposure in both newborn and adult animals. At P14 and P21, rates of LCBF decreased with hypoxia. These decreases were significant in 23 and 21 brain regions, respectively, belonging to all systems studied. These changes in LCBF are in quite good correlation with our previous data on the effects of acute hypoxia exposure on cerebral glucose utilization but the decrease in LCBF is of higher amplitude than the one in cerebral glucose utilization translating into a relative hypoperfusion at a constant metabolic level at P14 and P21. However, arterial blood pressure was reduced by 16 mmHg and arterial pCO 2 was significantly decreased at the two latter ages in hypoxic animals compared to controls. These two systemic factors, and mainly hypocapnia, are rather responsible for the cerebral hypoperfusion recorded at P14 and P21 in hypoxic rats whereas the circulatory response seems to be predominantly hypoxic at P10.

Deuterium chemical shift imaging for the estimation of cerebral perfusion in rabbit infarction model

In order to develop a new technique for the measurement of local cerebral blood flow (CBF), the deuterium chemical shift imaging (2H-CSI) technique, an application of in vivo nuclear magnetic resonance (NMR), was used for the estimation of cerebral perfusion in rabbit infarction model. The 2H chemical shift images of rabbit brain were obtained every 30 seconds before and after intravenous injection of deuterated saline. The changes in 2H NMR signal intensity documented that the cerebral perfusion in the damaged area due to infarction decreased obviously compared to that in the intact area. These findings indicate that the 2H-CSI technique can be applied to the measurement of local CBF. The readily availability and limited toxicity of deuterated water may make possible to use this method in clinical cases.

Effects of Prostaglandin E1 or Trimethaphan on Local Cerebral Blood Flow and Carbon Dioxide Reactivity During Cerebral Aneurysm Surgery

Effects of prostaglandin E1 (PGE1) or trimethaphan (TMP) on local cerebral blood flow (LCBF) and carbon dioxide (CO2) reactivity were studied in 26 patient undergoing cerebral aneurysm surgery for subarachnoid hemorrhage (SAH) under isoflurane anesthesia. Measurement of LCBF was made using a thermal gradient blood-flow meter. Hypotension was induced with a continuous i.v. infusion of PGE1 or TMP. The dose of PGE1 or TMP was adjusted to maintain the MAP at about 70 mm Hg, and CO2 reactivity was studied during and after PGE1 or TMP administration. PaCO2 was changed by the controlled hyperventilation. CO2 reactivity was evaluated by the following formula: % delta LCBF/delta PaCO2% mm Hg. Hypotensive drugs were discontinued at the completion of aneurysm clipping. Mean arterial pressure (MAP) decreased immediately after the start of either PGE1 or TMP. Heart rate (HR) did not change significantly in either group. LCBF decrease at 30 min after start of TMP administration (p < 0.05 compared with preinfusion value), whereas LCBF was unchanged during PGE1 administration. Neither PGE1 nor TMP affected CO2 reactivity during cerebral aneurysm surgery, whereas CO2 reactivity showed a close correlation with presurgical neurological status: before, rs = -0.523, p < 0.01; during, rs = -0.794, p < 0.01; after, rs = -0.643, p < 0.01. Comparison of the outcomes after aneurysm surgery demonstrated no significant difference between groups; however, there was a close correlation between presurgical neurological status and outcome in both groups (rs = 0.829, p < 0.01). These results suggest that PGE1 is preferable to TMP in inducing hypotension for cerebral aneurysm surgery because this drug maintains both LCBF and CO2 reactivity.

The Effect of Nicardipine on Carotid Blood Flow Velocity, Local Cerebral Blood Flow, and Carbon Dioxide Reactivity During Cerebral Aneurysm Surgery

We studied the effects of nicardipine (initial infusion rate 0.5 μ·kg−1·min−1) on blood flow velocity in the internal carotid artery, local cerebral blood flow (LCBF), and carbon dioxide reactivity in 20 patients undergoing craniotomy for cerebral aneurysm clipping under isoflurane anesthesia. The blood flow velocity in the internal carotid artery was measured at T0 and T3 by a 20-MHz pulsed ultrasound Doppler flowmeter. LCBF was measured by the thermal gradient blood flow meter. Group A consisted of 10 patients with a good neurologic status (Hunt and Kosnik Grade I); Group B consisted of 10 patients with a poor status (Grades II-IV). Nicardipine was infused until the mean arterial blood pressure decreased to about 75% of the initial value and was maintained at this level until the completion of aneurysm clipping. The measurements of hemodynamics and LCBF were performed after the exposure of the internal carotid artery (T0), and 10 and 30 min after the start of nicardipine (T1 and T2, respectively), before aneurysm clipping (T3), and 30 min after its discontinuation (T4). Carbon dioxide reactivity [% ÂLCBF/ÂPaCO2 (% / mm Hg)] was evaluated at T0, T3, and T4. Mean arterial blood pressure decreased after nicardipine infusion in both groups. LCBF did not change during nicardipine infusion in either group. Blood flow velocity increased significantly in Group A after nicardipine infusion from 45.1 ± 6.9 to 51.5 ± 6.4 cm/s (P < 0.05), but in Group B flow velocity did not change. Carbon dioxide reactivity did not change after nicardipine infusion but correlated with LCBF before (r2 = 0.495, P < 0.05), during (r2 = 0.706, P < 0.01), and after hypotension (r2 = 0.555, P < 0.05). These results suggest that nicardipine may be a useful drug to treat intraoperative hypertension during cerebral aneurysm surgery. (Anesth Analg 1993;76:1227-33)