CBF Changes Research Articles

CBF changes during brain activation: fMRI vs. PET

The changes in regional cerebral blood flow (rCBF) associated with the changes in neuronal activity are routinely measured both by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) techniques. However, direct comparison has not been performed to determine similarities and differences of PET and fMRI techniques in determining the rCBF response to brain activation. In the present study, a quantitative comparison of the functional rCBF maps obtained by PET and fMRI are made by performing an activation study in a single group of subjects under precisely controlled conditions and using identical visual stimuli. Twelve healthy volunteers participated in the activation study using the visual checkerboard stimulation with flip frequency at 8 Hz. By selecting the conjunctive pixels which activated on both PET and fMRI maps, the change in rCBF measured by fMRI was 36.95 ± 2.54%, whereas the value measured by PET was 38.79 ± 2.63%. Our results have demonstrated that there is no statistically significant difference ( P = 0.22) in the measurements of rCBF change between MRI and PET methods.

Electrical stimulation of the dorsal periaqueductal gray decreases volume of the brain infarction independently of accompanying hypertension and cerebrovasodilation

We investigated whether selective stimulation of neurons of the sympathoinhibitory ventral periaqueductal gray (VPAG), or sympathoexcitatory dorsal periaqueductal gray (DPAG), differentially modulates CBF and EEG and exerts neuroprotection. Electrical stimulation of either regions of PAG comparably elevated AP and CBF, whereas chemical stimulation with the d, l-homocysteine produced either sympathoinhibition accompanied by decrease in CBF from ventral region or sympathoexcitation accompanied by increase in CBF from dorsal region in nonspinalized rats. The CBF effects evoked from DPAG and VPAG by chemical stimulation were preserved in spinalized rats supporting that the evoked CBF responses result directly from stimulation and are not secondary to AP changes. Stimulation of either region, whether chemical or electrical, synchronized the EEG. To explore whether PAG stimulation might protect the brain against ischemic injury, in other rats the VPAG or DPAG were stimulated for 1 h (50 Hz, 1 s on/1 s off, 75–100 μA) and the middle cerebral artery occluded 72 h later. Stimulation of the DPAG, but not VPAG, significantly reduced infarction volumes relative to sham-stimulated controls as determined 24 h after occlusion. Elevations of AP and CBF did not differ between groups. We conclude: (a) intrinsic neurons of D- and VPAG differentially regulate CBF; (b) neurons of DPAG are neuroprotective independently of changes in CBF and/or AP. The DPAG effect on infarct volume may be related to the central neuroprotective pathway evoked by stimulation of the cerebellar FN.

Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment

This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75–77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82–84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.

Encephaloduroarteriosynangiosis with bifrontal encephalogaleo(periosteal)synangiosis in the pediatric moyamoya disease: the surgical technique and its outcomes.

To increase the blood flow of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) territories, we modified the "ribbon" procedure in combination with encephaloduroarteriosynangiosis (EDAS). This is referred to as "EDAS with bifrontal encephalogaleo(periosteal)synangiosis (EGS)." The surgical technique, clinical outcomes, complications, extent of revascularization, and changes in CBF in 67 pediatric MMD patients were retrospectively reviewed. The excellent and good clinical recovery rates were 57% and 31%. The rate for complete disappearance of TIA was 63%. All the bifrontal EGS made abundant collateral vessels in the ACA territory. When the EDAS with bifrontal EGS was performed in the first operation, collaterals of EGS sites developed more on the contralateral side of the EDAS. The arachnoid opening of the medial frontal lobe in the EGS site had no effect on the results. There was a positive correlation between the clinical outcome and the extent of angiographic revascularization. Improvements in the CBF and the reserve in ACA territory were observed in 57%. EDAS with bifrontal EGS resulted in excellent revascularization in both the MCA and ACA territories. The clinical and hemodynamic results were also excellent. This procedure may be an effective and safe surgical modality for the prevention of ischemia in the whole territory of the anterior circulation of the brain in pediatric MMD.

Reproducibility of the blood flow index as noninvasive, bedside estimation of cerebral blood flow.

To investigate the feasibility and reproducibility of the blood flow index (BFI) method for measuring cerebral blood flow. Prospective functional study in pediatric intensive care. 14 consecutive patients with median age of 2 months (range 1 days-11 years) requiring artificial ventilation, invasive arterial blood pressure monitoring, and central venous access. The first passage of an intravenous indocyanine green (ICG) bolus through the cerebral vasculature was monitored by noninvasive near-infrared spectroscopy. BFI was calculated by dividing maximal ICG absorption change by rise time. Reproducibility was evaluated by six ICG injections at 5-min intervals. Of all ICG injections 6% were canceled, and 4% were eliminated due to injection failures. Median BFI of 17 reproducibility determinations was 71 (range 12-213) and median coefficient of variation (CV) of BFI was 10% (4.9-18.5). The quantity of ICG bolus did not affect the CV (0.1 vs. 0.3 mg ICG/kg). Eight reproducibility tests in patients after cardiac surgery had smaller CV than the others, and the eight in newborns had higher CV than in older children. Patient parameters such as arterial blood pressure, endtidal CO(2), and percutaneous oxygen saturation were stable and showed CV below 2% during reproducibility determination. The BFI method allows rapid and repeated measurements of CBF with good feasibility and reproducibility. As a relative but not absolute measure of CBF, BFI seems to be suited for clinical evaluation of intraindividual CBF changes during determination of cerebrovascular reactivities or during therapeutic interventions.

537 Portal-pressure gradient reduction by K-canrenoate is not parallelled by sympathoinhibition in postviral preascitic child a cirrhosis with small oesophageal varices

We investigated whether selective stimulation of neurons of the sympathoinhibitory ventral periaqueductal gray (VPAG), or sympathoexcitatory dorsal periaqueductal gray (DPAG), differentially modulates CBF and EEG and exerts neuroprotection. Electrical stimulation of either regions of PAG comparably elevated AP and CBF, whereas chemical stimulation with the d,l-homocysteine produced either sympathoinhibition accompanied by decrease in CBF from ventral region or sympathoexcitation accompanied by increase in CBF from dorsal region in nonspinalized rats. The CBF effects evoked from DPAG and VPAG by chemical stimulation were preserved in spinalized rats supporting that the evoked CBF responses result directly from stimulation and are not secondary to AP changes. Stimulation of either region, whether chemical or electrical, synchronized the EEG. To explore whether PAG stimulation might protect the brain against ischemic injury, in other rats the VPAG or DPAG were stimulated for 1 h (50 Hz, 1 s on/1 s off, 75–100 μA) and the middle cerebral artery occluded 72 h later. Stimulation of the DPAG, but not VPAG, significantly reduced infarction volumes relative to sham-stimulated controls as determined 24 h after occlusion. Elevations of AP and CBF did not differ between groups. We conclude: (a) intrinsic neurons of D- and VPAG differentially regulate CBF; (b) neurons of DPAG are neuroprotective independently of changes in CBF and/or AP. The DPAG effect on infarct volume may be related to the central neuroprotective pathway evoked by stimulation of the cerebellar FN.

Cerebral circulation and sleep

Already Aristoteles discussed on restorative functions of sleep (cf. [1]). BorbeÂly [2] was the ®rst to show that the restorative function of sleep correlates to a reduction of homeostatic pressure built up during the day that can be assessed by the slow wave activity of the sleep electroencephalogram (EEG). The observation of a fronto-occipital power gradient in the EEG slow wave activity [3] points towards the existence of topographical differences in homeostatic functions of sleep. In accord with these electrophysiological data, recent studies with various techniques including positron emission tomography (PET) [4±6], functional magnetic resonance imaging (MRI) [8, 9] and laser Doppler owmetry (LDF) [10, 11] have demonstrated profound changes of cerebral blood ow (CBF) in various brain structures throughout the sleep-wake cycle. Based on the assumption that CBF is closely coupled with cerebral metabolism in the healthy brain these perfusion changes are thought to re ect modi®cations in the tissue metabolic state. Three review articles in this journal summarize our present state of knowledge about cerebral hemodynamics during sleep in healthy humans [12] as well as in patients with sleep disordered breathing [13] and cerebrovascular diseases [14]. In their review, Zaccoli et al. [12] ®rst summarize several studies (mainly with PET) demonstrating absolute and region-speci®c CBF changes during wakefulness, NREM and REM sleep as well as throughout the night [4±6]. While recognizing divergences in the results of these studies, the authors stress the

Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression.

Remitted major depressive disorder is a vulnerable clinical state, suggesting persistence of an underlying disease diathesis between episodes. To investigate neural correlates of such risk and to identify potential depression trait markers, euthymic unipolar patients in remission, acutely depressed patients, and never-depressed volunteers were studied before and after transient sad mood challenge. Common and differential changes in regional blood flow among the groups relative to the baseline state were examined with [(15)O]H(2)O positron emission tomography after provocation of sadness with autobiographical memory scripts. Mood provocation in both depressed groups resulted in regional cerebral blood flow (rCBF) decreases in medial orbitofrontal cortex Brodmann's area 10/11, which were absent in the healthy group. In the remitted group, mood provocation produced a unique rCBF decrease in pregenual anterior cingulate 24a. The main effects in healthy subjects, an rCBF increase in subgenual cingulate Brodmann's area 25 and a decrease in right prefrontal cortex Brodmann's area 9, were not present in the depressed groups. Mood challenge in unipolar euthymic patients in full remission unmasks an apparent depression trait marker. The pattern of acute CBF changes is distinct from that seen in euthymic healthy volunteers and mirrors the untreated depressed state seen during a major depressive episode and the pattern of change seen in depressed patients. These findings suggest that disease-specific modifications of pathways mediating transient mood changes are present in unipolar depression independent of clinical illness status. These findings have implications for understanding the vulnerability of remitted patients for illness relapse.

MR assessment of cerebral vascular response: A comparison of two methods

To compare the results and reproducibility of two MR-based methods of measuring the cerebrovascular response (CVR). In eight volunteers, CVR was assessed with two MR-based methods upon a challenge with acetazolamide. CVR was assessed by measuring changes in total cerebral blood flow (TCBF) using phase contrast (PC) MRI, and by measuring perfusion MRI. To assess reproducibility the measurements were repeated after 1 week. The average CVR with the PC-MRI method was 46% (SD = 16%), and for perfusion MR the measured CVR was 44% (SD = 16%). The coefficient of variation (COV) for PC-MRI was 28%, while perfusion MR had a COV of 26%. The limits of agreement between the two methods were -49% and 45%, demonstrating a lack of agreement between the two methods in terms of CVR estimation. CVR estimates based on PC-MRI and perfusion MRI showed reproducibility but a lack of agreement in healthy volunteers. This lack of agreement can be attributed to the different aspects of the CVR reflected by these methods: TCBF reflects changes in CBF, whereas our perfusion MRI method reflects cerebral blood volume (CBV).

Cerebral hemodynamics measured with simultaneous PET and near-infrared spectroscopy in humans

Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy- and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. In five healthy volunteers changes in CBF were induced in a randomized order by hyperventilation or inhalation of 6% CO 2. Arterial content of O 2 and CO 2 was measured several times during each scanning. Changes in deoxyhemoglobin (ΔHb), oxyhemoglobin (ΔHbO 2) and total hemoglobin (ΔHb tot) were continuously recorded with NIRS equipment. CBF and CBV was also determined in MRI-coregistered PET-slices in regions determined by the placement of the two optodes, as localized from the transmission scan. The PET-measurements showed an average CBV of 5.5±0.74 ml 100 g −1 in normoventilation, with an increase of 29% during hypercapnia, whereas no significant changes were seen during hyperventilation. CBF was 51±10 in normoventilation, increased by 37% during 6% CO 2 and decreased by 25% during hyperventilation. NIRS showed significant increases in oxygenation during hypercapnia, and a trend towards decreases during hyperventilation. Changes in CBV measured with both techniques were significantly correlated to CO 2 levels. However, ΔCBV NIRS was much smaller than ΔCBV PET, and measured NIRS parameters smaller than those predicted from the model. It is concluded that while qualitatively correct, NIRS measurements of CBV should be used with caution when quantitative results are needed.

Changes in Blood Flow and Oxygen Metabolism During Visual Stimulation in Carotid Artery Disease

Severe atherosclerotic disease of the carotid arteries may affect perfusion in the posterior circulation according to the degree of collateral supply. The purpose of this study was to determine whether the responses of regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) during neural stimulation are affected by the baseline perfusion or oxygen metabolism. We used PET to measure rCBF, rCMRO2, and regional oxygen extraction fraction (rOEF) in 13 patients with carotid artery steno-occlusive lesions at baseline and during visual stimulation. We examined whether the changes in CBF, CMRO2, and OEF during visual stimulation were correlated with the baseline values of these parameters in the visual cortex. With visual stimulation, rCBF increased in all patients, whereas rCMRO2 showed variable changes. The baseline rCMRO2 value showed a positive relationship with the degree of rCBF increase and a negative relationship to the degree of rCMRO2 increase. rCMRO2 decreased in patients with relatively high baseline rCMRO2 values, resulting in dissociation of the rCMRO2 response from the rCBF response. The rCBF increase was large in the region with an increased baseline rOEF value. These variable changes in rCBF and rCMRO2 resulted in a significant correlation between the values of rCBF and rCMRO2 during visual stimulation in contrast to the lack of such a correlation at baseline. In patients with cerebrovascular disease, neural stimulation may induce variable changes in rCBF and rCMRO2 according to the baseline perfusion and oxygen metabolism.

Salt-sensitive hypertension in conscious rats induced by chronic nitric oxide blockade

This study examined the effects of alterations in salt-intake on blood pressure (BP) in rats chronically treated intravenously with or without the nitric oxide synthase (NOS) inhibitor N G-nitro- l-arginine methyl ester (L-NAME) (8.6 mg/kg/day). The changes in mean arterial pressure (MAP), the renal cortical and medullary blood flow (CBF and MBF), and the sodium balance were determined by implanted optical fibers and laser-Doppler flow measurement techniques in the conscious rats. The results showed that high salt intake (7.4 mEq/day) elevates CBF (139% ± 15%), but has no significant effect on MAP or MBF in control rats; in L-NAME-treated rats, high salt intake elevates MAP, produces no change in CBF, and decreases MBF (51% ± 14%), as well as increasing the sodium balance (0.26 ± 0.23 mEq/day to 1.29 ± 0.47 mEq/day). The present experiments indicated that NO appears to maintain the MBF during high salt intake and to prevent the changes in MAP, and, in the absence of NO, salt-sensitive hypertension develops. Nitric oxide plays an important role in the development of salt-sensitive hypertension with the change of MBF.

Difference of Jugular Bulb Oxygen Saturation under Propofol, Enflurane and Isoflurane Anesthesia with Hydralazine-induced Deliberate Hypotension

Background: Hydralazine produces cerebral vasodilation, which could appear differently according to which kind of anesthetics was used. SjO, CBF and AJDO2 have been studied during general anesthesia with enflurane, isoflurane or propofol in 42 patients undergoing spinal surgery. Methods: Forty-two healthy adult patients were divided into Group P (Propofol-N2O, n = 15), Group E (Enflurane-N2O, n = 15) and Group I (Isoflurane-N2O, n = 12). During the course of the study, the anesthetic concentration was constant. Induced hypotension was provided with hydralazine 20 mg in combination with a continuous infusion of esmolol within 50-100g/kg/min. Arterial blood and jugular bulb blood were obtained and analyzed at normotensive and hypotensive period, respectively. SjO2, was compared within and between groups. Results: SjO values of Group P were 66.2 7.7%, and 81.5 ﾒ 6.1%, those of Group E were 79.5 5.6%, and 78.9 X 4.9% and those of Group I were 82.0 ･ 6.2%, and 84.4 ﾝ 3.7% at normotension and hypotension, respectively (P 0.05 between Group P and Group E, P 0.05 between Group P and Group I, P 0.05 within Group P). Conclusions: When the changes of CBF is assumed with that of SjO, it may be concluded that CBF increased with hydralazine-induced hypotension in propofol-N2O anesthesia. It may be suggested that hydralazine reverses propofol induced cerebral vasoconstriction.

Prolonged increase in ciliary beat frequency after short-term purinergic stimulation in human airway epithelial cells.

Stimulation of ovine airway epithelial cells with 10 microM ATP for 1 min at 25 degrees C transiently increased both cytoplasmic calcium (fura-2 epifluorescence microscopy) and ciliary beat frequency (CBF; differential interference contrast microscopy) with a similar time course. Identical purinergic stimulation of human airway epithelial cells at 25 or 35 degrees C, however, lead to an increase in CBF that outlasted the calcium transient at least 20 min. While a nitric oxide synthase inhibitor had no effect, pre-treatment of human cells with inhibitors of cAMP-dependent kinase (PKA), 10 microM myristoylated PKA-inhibitory peptide and 1 microM KT-5720, as well as an inhibitor of adenylyl cyclase, 1 mM SQ22536, blocked the prolonged, but not calcium-coupled CBF increase. Addition of PKA inhibitors after purinergic stimulation only partially reduced CBF from its elevated plateau. Prolonged CBF increases did not depend on adenosine production as 10 microM UTP had an effect similar to ATP and 8-sulphophenyl-theophylline did not block them. After increasing human CBF in a PKA-dependent manner to a stable plateau with forskolin (10 microM), ATP caused only a transient, calcium-coupled CBF increase. Calcium transients were necessary for both short-term and prolonged CBF changes as ATP failed to produce CBF increases after emptying calcium stores with 1 microM thapsigargin. These data suggest that in human, but not ovine airway epithelial cells, ATP-induced calcium transients activate a signalling cascade including adenylyl cyclase and PKA. The resulting prolonged CBF stimulation does not rely only on PKA activity, suggesting that the decay of CBF is influenced by ciliary phosphatase activity.

Neuroimaging--recent issues and future progresses

Recent advances in the technology of non-invasive neuroimaging techniques, include X-ray CT, magnetic resonance imaging, positron CT, etc. The trend of neuroimaging is from the diagnosis of the brain structural change to the functional localization of the brain function with accurate topographical data. Brain activation studies disclosed the responsible regions in the brain for various kinds of paradigms, including motor, sensory, cognitive functions. Another aspect of brain imaging shows the pathophysiological changes of the neurological disorders, such as Alzheimer's disease by abnormal CBF or metabolism changes. It is very important to note that the neurotransmitter receptor imaging is now available for various kinds of transmitters. We recently developed a new tracer for nicotinic type acetylcholine receptor, which might be involved in the pathophysiology of Alzheimer's disease and its treatment. In the near future, we will be able to visualize the proteins in the brain such as amyloid protein, which will make us to diagnose Alzheimer's patients accurately, and with respect to neuroscience research, not only neuronal functional localizations but also relationship between them will become important to disclose the functional aspects of the brain.

Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI.

Quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS) measurements of energy metabolism (i.e. cerebral metabolic rate of oxygen consumption, CMR(O2)), blood circulation (i.e. cerebral blood flow, CBF, and volume, CBV), and functional MRI (fMRI) signal over a wide range of neuronal activity and pharmacological treatments are used to interpret the neurophysiologic basis of blood oxygenation level dependent (BOLD) image-contrast at 7 T in glutamatergic neurons of rat cerebral cortex. Multi-modal MRI and MRS measurements of CMR(O2), CBF, CBV and BOLD signal (both gradient-echo and spin-echo) are used to interpret the neuroenergetic basis of BOLD image-contrast. Since each parameter that can influence the BOLD image-contrast is measured quantitatively and separately, multi-modal measurements of changes in CMR(O2), CBF, CBV, BOLD fMRI signal allow calibration and validation of the BOLD image-contrast. Good agreement between changes in CMR(O2) calculated from BOLD theory and measured by (13)C MRS, reveals that BOLD fMRI signal-changes at 7 T are closely linked with alterations in neuronal glucose oxidation, both for activation and deactivation paradigms. To determine the neurochemical basis of BOLD, pharmacological treatment with lamotrigine, which is a neuronal voltage-dependent Na(+) channel blocker and neurotransmitter glutamate release inhibitor, is used in a rat forepaw stimulation model. Attenuation of the functional changes in CBF and BOLD with lamotrigine reveals that the fMRI signal is associated with release of glutamate from neurons, which is consistent with a link between neurotransmitter cycling and energy metabolism. Comparisons of CMR(O2) and CBF over a wide dynamic range of neuronal activity provide insight into the regulation of energy metabolism and oxygen delivery in the cerebral cortex. The current results reveal the energetic and physiologic components of the BOLD fMRI signal and indicate the required steps towards mapping neuronal activity quantitatively by fMRI at steady-state. Consequences of these results from rat brain for similar calibrated BOLD fMRI studies in the human brain are discussed.

The effect of tranexamic acid on cochlear blood flow in guinea pigs measured by laser Doppler flowmetry

Objective: This study investigated the vasoactive effect of tranexamic acid on the cochlear blood flow in guinea pigs. Method: 3 ml solution (infusion speed, 0.5 ml/min) containing different concentrations of tranexamic acid was intravenously infused into 15 guinea pigs under general anesthesia. The guinea pigs were grouped according to four levels of dosage of the medicine (470 mg/kg, n=6; 220 mg/kg, n=3; 4 mg/kg, n=3; 1 mg/kg, n=3). Before administering medicine, saline solution was administered in similar volume and speed as a control. The cochleas were surgically exposed and laser Doppler flowmetry monitored cochlear blood flow volume (CBF). The left femoral artery was cannulated to permit a transducer to monitor systemic blood pressure (BP). Results: (1) Stimulatory effect of tranexamic acid on CBF was dose-dependent at concentrations of 1–470 mg/kg and, (2) the time course of changes in CBF was almost identical to that in BP following tranexamic acid administration. Conclusion: Preliminary findings suggest that intravenous administration of tranexamic acid increases CBF due to vasomotorial mechanism effect on BP.

Regional CBF changes with risperidone in schizophrenic patients: Comparison with haloperidol

Regional CBF changes with risperidone in schizophrenic patients: Comparison with haloperidol

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.

Roles of ANG II and bradykinin in the renal regional blood flow responses to ACE inhibition in sodium-depleted dogs.

The relative contributions of ANG II and bradykinin (BK) to the renal regional blood flow responses during angiotensin-converting enzyme (ACE) inhibition remain unclear. This study was performed to evaluate renal cortical (CBF) and medullary blood flow (MBF) responses to intrarterial administration of enalaprilat (33 microg. kg(-1). min (-1)) after blockade of the ANG II AT(1 )receptors with candesartan (100 microg) in 7 dogs fed a low-salt diet (0.01%) for 5 days. Laser-Doppler flowmetry was used to measure relative changes in CBF and MBF. Candesartan alone increased CBF (+20 +/- 2%) and MBF (+22 +/- 7%). Enalaprilat infusion after candesartan administration resulted in further increases in both CBF (+21 +/- 5%) and MBF (+41 +/- 8%). However, the relative changes in MBF were significantly greater (P < 0.01) than those in CBF. Administration of the BK B(2) receptor blocker icatibant (300 microg) after enalaprilat returned CBF and MBF to values seen with candesartan alone. These data support a substantive role for BK potentiation during ACE inhibitor-induced renal vasodilation in dogs maintained on a low-sodium diet, with a relatively greater effect on MBF compared to CBF.