A comparison of the functional vulnerability of the cerebral cortex and thalamus to acute ischemia

Using cerebral cortical and thalamic ischemia models produced in mongrel dogs, the reversibility of short-latency somatosensory-evoked potentials (SSEPs) and the effects of ischemic brain edema on reversibility were compared. The mean systemic blood pressure (MSBP) of animals was reduced by exsanguination until cortical SSEPs disappeared, and was held constant at that level. The MSBP was recovered by autogenous blood transfusion at 30 minutes (subgroup A), 60 minutes (subgroup B) and 90 minutes (subgroup C) after SSEP disappearance in the cortical ischemia group; and at 15 minutes (subgroup D) and 30 minutes (subgroup E) after SSEP disappearance in the thalamic ischemia group. Local cerebral blood flows (lCBF) were measured and SSEPs were monitored serially up to 2 hours after blood transfusion. At the end of measurement, the leakage of Evans blue was evaluated and brain tissue water content was measured. Cortical SSEPs disappeared when lCBF in the right cerebral cortex, measured by hydrogen clearance method decreased to 18.4 +/- 5.4 ml/100 g/min (mean +/- SD) and neuronal transmission failure in thalamus occurred when thalamic blood flow decreased to 10.0 +/- 3.3 ml/100 g/min. After blood transfusion. SSEP reappeared in all 12 animals in subgroup A, but did not appear in 2 of 9 animals in subgroup B and in all of 7 animals in subgroup C.(ABSTRACT TRUNCATED AT 250 WORDS)     

The novel dihydronaphthyridine Ca2+ channel blocker CI-951 improves CBF, brain pHi, and EEG recovery in focal cerebral ischemia

The effects of the novel dihydronaphthyridine Ca2+ antagonist CI-951 on focal cerebral ischemia were assessed during MCA occlusion in 30 white New Zealand rabbits under 1.0% halothane anesthesia. In vivo brain pHi and focal CBF were measured with umbelliferone fluorescence. Baseline normocapnic brain pHi and CBF were 7.02 +/- 0.02 and 48.4 +/- 2.9 ml/100 g/min, respectively. In the severe ischemic regions, 15 min postocclusion brain pHi and CBF were 6.62 +/- 0.04 and 14.4 +/- 0.7 ml/100 g/min in controls vs. 6.60 +/- 0.02 and 12.9 +/- 2.3 ml/100 g/min, respectively, in animals destined to receive CI-951. Twenty minutes after MCA occlusion, CI-951 was administered at 0.5 microgram/kg/min and brain pHi and CBF were determined in both regions of severe and moderate ischemia for 4 h postocclusion. Control severe ischemic sites demonstrated no significant improvement in brain pHi and only mild increases in CBF over the next 4 h. CI-951 caused significant improvement in both of these parameters. Postocclusion 4 h brain pHi and CBF measured 6.69 +/- 0.04 and 18.5 +/- 3.2 ml/100 g/min in controls vs. 7.01 +/- 0.04 and 41.7 +/- 5.3 ml/100 g/min, respectively, in CI-951 animals (p less than 0.001). Similar improvements were observed in moderate ischemic sites. In animals that demonstrated postocclusion EEG attenuation, 75% of CI-951 animals had EEG recovery as compared to 18% in controls. CI-951 may be a useful therapeutic agent for focal cerebral ischemia if histological and outcome studies verify these data.     

The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion

Summary The behavior of the blood-brain barrier (BBB) was studied in cats following release after 1-h middle cerebral artery (MCA) occlusion. The regional cerebral blood flow (rCBF) was determined by hydrogen clearance method in the caudate nucleus and the cerebral cortex. The BBB was assayed with Evans blue (EB) tracer and by immunohistochemical peroxidaseantiperoxidase (PAP) method. Following release of MCA occlusion, there were two openings of the BBB, separated by a refractory period. The first opening, occurred shortly after recirculation; this was associated with rCBF below 15 ml/100 g/min during the ischemic period and a pronounced reactive hyperemia promptly following release of MCA occlusion. A refractory period of the BBB was indicated by the absence of EB leakage in cats injected with the tracer 30 min before killing at 3 h after recirculation, although the rCBF values in these animals were even lower (6±1 ml/100 g/min) during occlusion, and all of them showed a pronounced hyperemia after recirculation. The occurrence of the previous BBB opening in these animals was confirmed by the PAP staining. The second opening of the BBB was observed at 5 and 72 h after recirculation in cats which were injected with EB 30 min before killing, and which showed rCBF below 15 ml/100 g/min during occlusion, followed by a pronounced reactive hyperemia. No EB extravasations were observed at any time in cats in which the rCBF during occlusion was above 15 ml/100 g/min and which failed to show a marked reactive hyperemia.     

Cerebral blood flow, glucose utilization, regional glucose, and ATP content during the maturation period of delayed ischemic injury in gerbil brain

Coupling between local perfusion and metabolism was examined in Mongolian gerbils during the development of delayed neuronal death using a combination of double-tracer autoradiography and imaging of local energy state. Animals were anesthetized with 1.5% halothane and forebrain ischemia was produced by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 6 h and 1, 2, or 4 days. At the end of the experiment, regional cerebral blood flow (CBF) and glucose utilization (CMRglc) were determined in identical brain section with [131I]iodoantipyrine and [14C]deoxyglucose, respectively. Adjacent sections were taken for imaging of ATP and glucose using substrate-specific bioluminescence reactions. In the CA1 subfield of control animals, CBF and CMRglc amounted to 81 +/- 8 ml 100 g-1min-1 and 69 +/- 2 mumol 100 g-1min-1, respectively, and the calculated CBF/CMRglc ratio was 1.18 +/- 0.12 ml/mumol (mean +/- SD). After ischemia, the CBF/CMRglc ratio increased to 1.31 +/- 0.14, 1.43 +/- 0.16, 1.45 +/- 0.16, and 1.56 +/- 0.18 ml/mumol following 6 h and 1, 2, or 4 days recirculation, respectively. Glucose levels did not change during the 6 h to 4 day recirculation period in the hippocampal CA1 subfield. In the same region, ATP levels were unchanged during 6 h to 2 day postischemic recovery but reduced to about 70% after 4 days of recirculation. The results indicate that a mismatch of the flow--metabolism couple following transient ischemia does not appear to contribute to the postischemic maturation of delayed neuronal death in selectively vulnerable brain regions.     

Correlation between cerebral blood flow, somatosensory evoked potentials, CT scan grade and neurological grade in patients with subarachnoid hemorrhage.

Cerebral blood flow (CBF) and central conduction time (CCT) were recorded from 58 subarachnoid hemorrhage patients and from 49 age-matched controls. CBF was calculated following Xenon inhalation and CCT was determined from somatosensory evoked potentials (SSEP's) following median nerve stimulation. Each patient had a CT scan on the day of admission which was graded from I-IV. CBF, CCT and neurological grade (Hunt and Hess classification) were concomitantly recorded 1, 4, 7 and 14 days after subarachnoid hemorrhage. Mean CBF was highest in patients with neurological grades I and II (48.6 +/- 12.3 and 48.1 +/- 10.3 ml/100gm/min respectively) and lowest in patients with neurological grade IV (37.3 +/- 9.6 ml/100gm/min). Patients in neurological grade I or II had mean CBF and CCT measurements that were significantly different from those obtained from patients in neurological grade IV (P less than 0.05). Neurological grade and CT scan grade correlated with CBF (P less than 0.0001) better than CCT (P = 0.015). Unexpectedly low CBF's from patients in neurological grades II and III (less than 37 and less than 31 ml/100gm/min respectively) failed to significantly prolong CCT suggesting CCT is unable to detect marginal ischemia. A significant correlation between CBF and CCT occurred only when CBF was less than 30 ml/100gm/min (R = 0.75, P = 0.05). It appears that prolonged CCT is associated with a drop in CBF only when CBF drops below a certain threshold.     

Recirculation after cerebral ischemia. Simultaneous measurement of cerebral bloodflow, brain edema, cerebrovascular permeability and cortical EEG in the rat

The 4-vessel occlusion rat model of cerebral ischemia was modified to permit the simultaneous measurement of cerebral blood flow (hydrogen clearance), brain edema (specific gravity), cerebrovascular permeability (14C-AIB) and electrocardiogram. Surgery was performed in one stage in the anesthetised, paralysed and ventilated rat and severe hemispheric ischemia was produced in all animals. Electrode implantation did not alter cortical specific gravity or Ki for 14C-AIB. During 4-vessel occlusion mean cortical CBF was 5.8 +/- 1.4 ml-1 100 g-1 min. and this was associated with an isoelectric ECoG; 15 min of ischemia produced a significant reduction in mean cortical specific gravity (increase in brain edema). Following 15 min ischemia, 180 min of recirculation were permitted. Post-ischemic blood flow showed an immediate hyperemia (CBF = 202 +/- 12 ml-1 100 g-1 min.) followed by hypoperfusion (CBF = 58 +/- 8 ml-1 100 g-1 min). There was an early further decrease in cortical specific gravity. Further recirculation led to a significant increase in cortical specific gravity (resolution of brain edema). The transfer constant (Ki) for 14C-AIB was not altered at any stage in recirculation. This appears to be a model of pure cytotoxic edema until 180 min recirculation after 15 min cerebral ischemia. Recirculation permitted return of cortical electrical activity.     

Cerebral blood flow requirement for brain viability in newborn infants is lower than in adults

Measurements of regional cerebral blood flow (CBF) with positron emission tomography in adult humans with cerebrovascular disease have demonstrated consistently that values below 10 ml/(100 gm.min) occur only in infarcted brain. Although experimental data suggest that the newborn brain may be more resistant to ischemic injury than the adult brain, the minimum CBF necessary to sustain neuronal viability in newborn infants is unknown. We have measured CBF with positron emission tomography in 16 preterm and 14 term newborn infants and have determined the relationship between CBF and subsequent brain function as assessed by neurological examination and developmental assessment. The range of mean CBF in the preterm infants was 4.9 to 23 ml/(100 gm.min) and the range of mean CBF in the term infants was 9.0 to 73 ml/(100 gm.min). Five preterm infants and one term infant with mean CBF less than 10 ml/(100 gm.min) survived. Three of these 5 preterm infants, with mean CBF of 4.9, 5.2, and 9.3 ml/(100 gm.min), respectively, have normal neurological examinations and Bayley Scales of 80 or greater at 6, 6, and 24 months of age, respectively. One (mean CBF 6.9) has normal cognitive development (Bayley 103) and a mild spastic diplegia at age 19 months, and one infant (mean CBF 6.2) has a left hemiparesis and a Binet IQ score of 70 at age 33 months. The term infant, with a mean CBF of 9.0 ml/(100 gm.min), was developing normally when he died of sepsis at age 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

CBF and CBF/PCO2 reactivity in childhood strangulation.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrovascular and cerebrometabolic effects of intracarotid infused platelet-activating factor in rats

Platelet-activating factor has been implicated in a variety of disease processes including ischemic brain injury and endotoxic shock, but its effects on cerebral blood flow (CBF) and metabolism in normal brain have not been described. The effects of platelet-activating factor on global CBF (hydrogen clearance) and the global cerebral metabolic rate for oxygen (CMRO2) were studied in halothane-N2O anesthetized Wistar rats. Hexadecyl-platelet-activating factor infused into the right carotid artery (67 pmol/min) for 60 min decreased mean arterial pressure (MAP) from 122 +/- 4 (x +/- SEM) to 77 +/- 6 mm Hg and CBF from 159 +/- 12 to 116 +/- 14 ml/100 g/min (p less than 0.002). In contrast, CMRO2 increased from 9.7 +/- 0.9 to 11.7 +/- 1.1 ml/100 g/min after 15 min (p less than 0.05). In controls rendered similarly hypotensive by blood withdrawal and infused with the platelet-activating factor vehicle, CMRO2 was unchanged, whereas CBF transiently decreased then returned to baseline at 60 min. These cerebrovascular and cerebrometabolic effects of PAF are reminiscent of and may be relevant to hypoperfusion and hypermetabolism observed after global brain ischemia and in endotoxic shock.     

Ischemic brain edema and the osmotic gradient between blood and brain

The relationship of the osmotic pressure gradient between blood and brain, and the development of ischemic brain edema was studied. Focal cerebral ischemia was produced by left middle cerebral artery occlusion in rats. Brain osmolality was determined with a vapor pressure osmometer, brain water content by wet-dry weight, and tissue sodium and potassium contents by flame photometry. Permeability of the BBB was tested by Evans blue. Measurements were made from the ischemic cortex within 14 days of occlusion. Brain osmolality increased from 311 +/- 2 to 329 +/- 2 mOsm/kg by 6 h after occlusion. Serum osmolality did not change significantly. The osmotic gradient between blood and brain peaked at approximately 26 mOsm/kg. Brain osmolality then decreased to 310 +/- 2 mOsm/kg by 12 h after occlusion and remained at about that same level. Water content increased progressively within 1 day of occlusion, then gradually decreased by 14 days. Brain tissue sodium plus potassium content did not increase within 6 h of occlusion, and Evans blue extravasation was not seen within that time. These findings indicate that an osmotic pressure gradient contributes to the formation of edema only during the early stage of cerebral ischemia. Furthermore, the increase in brain osmolality is not related to tissue electrolyte change or BBB disruption to protein.     

The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts

Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 +/- 2.5 ml/100 gm/min (mean +/- SEM) and was in every patient lower than that in C (33.1 +/- 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 +/- 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 +/- 1.5). In Group I, region I showed a CMRGlc(N)/CMRO2 ratio of 0.22 +/- 0.06 and a CpH of 6.83 +/- 0.06. In Group 2, the same ratio in the region I was 0.58 +/- 0.09 and the CpH was 7.12 +/- 0.05. The CMRGlc (N)/CMRO2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRO2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed.     

Cerebral and cerebellar blood flow autoregulations in acutely induced cerebral ischemia in spontaneously hypertensive rats--transtentorial remote effect

Autoregulation of cerebral (CBF) and cerebellar blood flow (CeBF) was studied before, during and after acutely induced cerebral ischemia in spontaneously hypertensive rats. Cerebral ischemia of the supratentorial portion was induced for one hour by bilateral carotid artery ligation (BCL). The animals were artificially ventilated and the blood flow was measured with a hydrogen clearance technique. To test the autoregulation, the blood pressure was stepwise lowered by bleeding and maintained at a new level, i.e. 15% or 30% lower than the baseline values before, during and after cerebral ischemia. At the preischemic state, CBF and CeBF were 52.1 +/- 6.2 and 58.9 +/- 4.6 ml/100 g/min (mean +/- SEM), of which autoregulations were normally preserved. Following BCL, CBF was markedly decreased to about 10% of control value while CeBF was minimally reduced to 46.9 +/- 8.6 ml/100 g/min (80%). At the ischemic state, CBF became almost zero flow during hypotension. CeBF was also reduced to 74% and further to 58% of the resting value by 15% and 30% decrease in the blood pressure, respectively, indicating impaired CeBF autoregulation. At the 30 min post-ischemic state, CBF was recovered to 48.0 +/- 4.9 and CeBF to 53.9 +/- 5.4 ml/100 g/min. Autoregulation of CBF was still abolished, whereas CeBF was kept constant by 15% fall of blood pressure and slightly reduced to 84% by 30% hypotension, indicating almost recovery of CeBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral protective effect of flunarizine in a canine model of cerebral ischemia

Recently there is the hypothesis proposing that ischemic brain damage is associated with intracellular accumulation of calcium (Ca++). Therefore a variety of experiments have been carried out to investigate whether a Ca++-entry blocker was able to protect against brain damage caused by ischemia. The purpose of the present experiment is to study the protective effects of a Ca++ antagonist, flunarizine, on cerebral ischemia. In this experiment fifteen dogs were subjected to ischemia, using the "canine model of the completely ischemic brain regulated with a perfusion method" in which the cerebral blood flow (CBF) can be fully regulated. Five animals served as untreated controls, ten received treatment with flunarizine (1 mg/kg in five dogs and 3 mg/kg in five dogs, respectively). This agent was administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal value while monitoring CBF by means of a laser-Doppler flow meter. After one hour CBF was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. At the end of the experiments, the degree of extravasation of Evans blue in the excised brain was examined. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the groups treated with flunarizine, remarkable recovery of EEG was found following recirculation in a dose dependent fasion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of reperfusion therapy on cerebral blood flow in acute stroke.

The effect of reperfusion therapy on cerebral blood flow (CBF) in acute cerebral ischemia was studied using xenon-enhanced computed tomography (XeCT). The XeCT CBF studies of 10 patients were evaluated before and after thrombolytic therapy. CBF evidence of reperfusion was evaluated in relation to the angiographic results and the clinical outcomes. Six patients had occlusions of the middle cerebral artery and four of the internal carotid artery. The mean CBF of the ischemic areas before attempted reperfusion was 9 +/- 3 mL/100g/min compared with 34 +/- 9 mL/100g/min in the contralateral asymptomatic region (P<.001). Intra-arterial-thrombolysis was performed in nine patients, and in one patient the intravenous route was used. Reperfusion of the ischemic region was shown in 9 of 10 patients, both angiographically and with the XeCT CBF studies (the mean CBF increased from 9 +/- 3 mL/100g/min to 32 +/- 10 mL/100g/min, P<.001). Among the nine successfully reperfused patients, seven were neurologically improved, one was unchanged, and one died. The mean National Institutes of Health stroke scale in the eight reperfused survivors was 12 on admission and decreased to 6 on discharge. XeCT CBF measurements are correlated with the angiographic results and can assist in the understanding of the effects of thrombolytic therapy on CBF in acute stroke. Re-establishment of CBF is associated with an improved clinical outcome but exceptions can be found. Reperfusion can occur in ischemic brain regions even with very low CBF (approaching 0 mL/100g/min) although it is not associated with prevention of infarction.     

Xenon computed tomography measuring cerebral blood flow in the determination of brain death in children

Local cerebral blood flow was measured using stable xenon computed tomography in 21 children, 10 of whom were clinically brain dead and had electrocerebral silence as determined by electroencephalography. Radioisotopic brain scanning in 9 patients showed no visible cerebral activity in all patients and minimal residual sagittal sinus activity in 4. In this population, mean cerebral blood flow as measured by xenon computed tomography was 1.3 +/- 1.6 ml/min/100 gm. Respiratory support was discontinued in 8 patients, and 2 patients had cardiac arrest. Eleven profoundly comatose children who did not meet all clinical criteria for brain death and who had markedly suppressed but not isoelectric electroencephalograms had an average cerebral blood flow of 33.5 +/- 16.3 ml/min/100 gm. There was no difference in cerebral blood flow in those children who survived (30.4 +/- 16.3 ml/min/100 gm; n = 7) compared with those who died acutely (38.3 +/- 14.3 ml/min/100 gm; n = 4). Two patients who survived had average total flows of only 11.8 and 12.1 ml/min/100 gm. Our findings suggest that in infants and children older than 1 month, (1) cerebral blood flow below approximately 10 ml/min/100 gm is consistent with clinical brain death, (2) cerebral blood flow of less than 5 ml/min/100 gm is consistent with no flow as demonstrated by radionuclide techniques, and (3) flow of more than 10 to 15 ml/min/100 gm is associated with the potential for survival.     

Evaluation of cerebral hemodynamics with perfusion CT]

We report on the evaluation of cerebral ischemic lesions with perfusion CT. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of 52 patients mostly with ischemic cerebrovascular disease were analysed using the box-modulation transfer function method with 30 ml of contrast medium intravenously injected at 5 ml/sec. CBF, CBV and MTT of the middle cerebral artery (MCA) territory were 43.5 +/- 4.6 ml/100 g/min, 1.9 +/- 0.2 ml/100 g and 2.9 +/- 0.6 seconds at the unaffected side, and 37.7 +/- 7.3 ml/100 g/min, 2.1 +/- 0.3 ml/100 g, 3.7 +/- 0.9 seconds at the lesion side with stenosis or occlusion in the main MCA trunks or internal carotid artery, respectively. A statistically significant difference was shown in CBF and MTT values. Furthermore, there was a close correlation in CBF values of MCA territories between Xe-CT and perfusion CT (r = 0.645, n = 76, p < 0.0001). MTT showed a positive correlation with CBV in those subjects when MTT was below 4.1 seconds (r = 0.526, p < 0.0001, n = 83). MTT also showed a negative correlation with CBF in those patients when MTT indicated more than 4.1 seconds (r = 0.818, p < 0.001, n = 21). These results suggest that the progression of cerebral ischemia may be classified in 4 stages using perfusion CT. The stages are as follows: stage 0; normal CBF without prolonged MTT and increased CBV, stage 1; relatively increased CBV, stage 2; significantly prolonged MTT, and stage 3; significantly decreased CBF with prolonged MTT.     

Tomographic analysis of CBF in cerebral infarction

Cerebral perfusion was examined in various types of occlusive disease by computed tomographic CBF method. The method utilized has several advantages over conventional studies using isotope, providing high resolution images in a direct relation to CT anatomy. Ten representative cases were presented from 25 consecutive cases of occlusive disease studied by this method. The method included inhalation of 40 to 60% xenon with serial CT scanning for 25 min. K (build-up rate), lambda (partition coefficient) and CBF values were calculated from HU for each pixel and Xe in expired air, based on Fick's principle, and displayed on CRT as K-, lambda- and CBF-map separately. CBF for gray matter of normal control was 82 +/- 11 ml/100 gm/min and that for white matter was 24 +/- 5 ml/100 gm/min. The ischemic threshold for gray matter appeared to be approximately 20 ml/100 gm/min, as blood flow in focus of complete infarction was below this level. Blood flow between 20-30 ml/100 gm/min caused some change on CT, such as localized atrophy, cortical thinning, loss of distinction between gray and white matter and decreased or increased density, which were considered to be compatible with pathological changes of laminar necrosis or gliosis with neuronal loss. In a case with occlusion of middle cerebral artery with subsequent recanalization, causing hemorrhagic infarct, hyperemia was observed in the infarcted cortex that was enhanced by iodine. Periventricular lucency observed in two cases, where blood flow was decreased below threshold, could be classified as "watershed infarction" mainly involving white matter. In moyamoya disease, blood flow in the anterior circulation was decreased near ischemic level, whereas that in basal ganglia and territory of posterior cerebral artery was fairly preserved, which was compatible with general angiographic finding of this disease.     

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1 min-1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.     

Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia

The present study was designed to clarify the effect of blood glucose level on cerebral blood flow and metabolism during and after acute cerebral ischemia induced by bilateral carotid ligation (BCL) in spontaneously hypertensive rats (SHR). Blood glucose levels were varied by intraperitoneal infusion of 50% of glucose (hyperglycemia), insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). Cerebral blood flow (CBF) in the parietal cortex and thalamus was measured by hydrogen clearance technique, and the supratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. In non-ischemic animals, blood glucose levels had no influence on the supratentorial lactate, pyruvate or adenosine triphosphate (ATP) concentrations. In ischemic animals, however, cortical CBF was reduced to less than 1% of the resting value at 3 hours after BCL. However, there were no substantial differences of CBF during and after ischemia among 3 glycemic groups. Cerebral lactate in the ischemic brain greatly increased in hyperglycemia (34.97 +/- 1.29 mmol/kg), moderately in normoglycemia (23.43 +/- 3.13 mmol/kg) and less in hypoglycemia (7.20 +/- 1.54 mmol/kg). In contrast, cerebral ATP decreased in hyperglycemia (0.93 +/- 0.19 mmol/kg) as much as it did in normoglycemia (1.04 +/- 0.25 mmol/kg), while ATP reduction was much greater in hypoglycemia (0.45 +/- 0.05 mmol/kg). At 1-hour recirculation after 3-hour ischemia, ATP tended to increase in all groups of animals, indicating the recovery of energy metabolism. Such metabolic recovery after recirculation was good in hypo- and normoglycemia, and was also evident in hyperglycemia. Our results suggest that hyperglycemia is not necessarily an unfavorable condition in acute incomplete cerebral ischemia.