Desflurane affords greater protection than halothane against focal cerebral ischaemia in the rat

Background. We studied the potential neuroprotective effectsof halothane and desflurane, compared with the awake state,on infarct size following 2 h of intraluminal middle cerebralartery occlusion (MCAo) and 22 h of reperfusion. Methods. Male Sprague–Dawley rats were anaesthetized withdesflurane or halothane, intubated, and mechanically ventilated.Mean arterial pressure (MAP), blood gases, and pH were controlled.Body temperature was maintained at 37.5–38°C. Animalswere assigned to one of four groups according to the anaesthetictype (halothane or desflurane) and the duration of anaesthesia:‘short-duration’, during the preparation only; ‘long-duration’,during both preparation and ischaemia. Twenty-four hours afterMCAo, infarcts were visualized by staining with 2,3,5-triphenyltetrazoliumchloride. Two additional groups of rats were subjected to thesame protocol as that of long-duration halothane and long-durationdesflurane with additional pericranial temperature measurementsmade. Results. Physiological parameters were comparable between thegroups but MAP was higher (P<0.0001) in the short-durationgroups. In the short-duration groups, cerebral infarct volumeswere not significantly different between anaesthetics (short-durationhalothane: 288 (61) mm³, mean (SD); short-duration desflurane:269 (71) mm³, P>0.56). Compared with the awake state (short-durationgroups), halothane and desflurane significantly reduced infarctvolumes (long-duration halothane: 199 (54) mm³, P<0.0047vs short-duration halothane; long-duration desflurane: 121 (55)mm³, P<0.0001 vs short-duration desflurane). The mean infarctvolume in the long-duration desflurane group was significantlylower than that in the long-duration halothane group (P<0.0053).Pericranial temperatures were similar in the desflurane andhalothane long-duration groups (P>0.17). Conclusions. In rats, desflurane-induced neuroprotection againstfocal cerebral ischaemia was greater than that conferred byhalothane. Br J Anaesth 2003; 91: 390–6     

A comparison of the area of histochemical dysfunction after focal cerebral ischaemia during anaesthesia with isoflurane and halothane in the rat

The investigations that have thus far evaluated the cerebral protective properties of isoflurane have provided conflicting results. Protection would be most likely to occur in the circumstances of incomplete cerebral ischaemia in which there is a penumbral zone of marginal perfusion. The present investigation sought to evaluate further the protective properties of isoflurane in that circumstance. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats anaesthetized with 1.2 MAC concentrations of either halothane or isoflurane. At the end of four hours of MCAO, the brains were removed, sectioned and incubated in the histochemical stain 2-3-triphenyltetrazolium (TTC). An image analysis system was used to measure the area of reduced or absent TTC staining in four coronal planes spanning the distribution of the middle cerebral artery. There was no difference between halothane and isoflurane anaesthetized animals with respect to the area of brain with evidence of histochemical dysfunction. It is concluded that isoflurane is not protective (relative to the status of halothane anaesthetized control animals) when administered at 1.2 MAC concentration during four hours of focal (incomplete) cerebral ischaemia in the rat.     

Effect of propofol on reperfusion injury after regional ischaemia in the isolated rat heart

Free oxygen radicals and intracellular calcium homeostasis play important roles in the development of myocardial reperfusion injury. Propofol is a radical scavenger with calcium channel blocking properties. We have investigated the effects of propofol on myocardial reperfusion injury. We used an isolated rat heart model where heart rate, ventricular volume and perfusion pressure were constant. The left anterior descending coronary artery (LAD) was occluded for 30 min and reperfused for 2 h. We studied an untreated control group, an Intralipid group (1 microliter ml-1) and a propofol group (Intralipid 1 microliter ml-1 and propofol 1 microgram ml-1) (n = 12 each). Drugs were infused for 20 min starting 5 min before reperfusion. We measured left ventricular developed pressure (LVDP), coronary flow and infarct size. LAD occlusion reduced mean LVDP from 129 (SEM 4) to 36 (3) mm Hg and mean coronary flow from 12.2 (0.3) to 5.2 (0.2) ml min-1. During reperfusion, LVDP recovered to 98 (4) mm Hg and coronary flow to 11.9 (0.4) ml min-1. Haemodynamic variables were similar in all groups. Propofol had no effect on infarct size compared with the Intralipid group (25.0 (3.7) vs 26.9 (3.3)% of the area at risk; P = 0.89). Infarct size in the Intralipid group tended to be smaller compared with the control group (34.8 (3.2)%; P = 0.19). We conclude that propofol, at a clinically relevant concentration, provided no protective effect against myocardial reperfusion injury in the rat heart in vitro.      

Comparative effects of propofol and halothane on outcome from temporary middle cerebral artery occlusion in the rat.

Because propofol has cerebral effects similar to those observed for barbiturates, we postulated that it too might offer protection against a focal cerebral ischemic insult. Spontaneously hypertensive male rats were anesthetized with halothane (in 50% O2/balance N2), and their tracheas were intubated and their lungs mechanically ventilated. A right subtemporal craniectomy was performed and a 10-0 suture placed around the middle cerebral artery. Rats were then randomly assigned to one of two anesthetic groups. In one half of the rats (n = 14), the inspired halothane concentration was reduced to 0.5-0.7%. In the remainder (n = 14), halothane was discontinued, and an intravenous infusion of 1% propofol was given in doses sufficient to produce and maintain electroencephalographic burst suppression. The middle cerebral artery was then reversibly ligated for 2 h while pericranial temperature was maintained at 37.0 +/- 0.1 degrees C (mean +/- SD). After the ligature was removed and reperfusion confirmed, all rats were allowed to recover for 96 h. Neurologic evaluations were performed at both 24 and 96 h postischemia. The rats were then killed and the brains removed, frozen, sectioned, and stained with nitro blue tetrazolium. Infarct volume was determined by computerized planimetry. Physiologic values were similar between anesthetic groups, although plasma glucose was significantly greater during ischemia in the halothane group (125 +/- 25 vs. 83 +/- 8 mg/dl, P less than 0.001). At both 24 and 96 h postischemia, neurologic deficits were mild but without a difference between groups. Neurologic scores at 96 h postischemia correlated with cerebral infarct volume (r = 0.49, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

可乐定对丙泊酚麻醉中海马去甲肾上腺素释放的影响

目的 通过观察大鼠在丙泊酚麻醉中海马去甲基肾上腺素(NA)的释放效应,探讨中枢性NA机制在丙泊酚麻醉中的作用。方法 采用微透析技术检测大鼠海马组织细胞外液NA的浓度。20只雄性大鼠,随机分为两组。单纯丙泊酚(A)组:分别以10和60 mg·kg-1·h-1的速度各静注45min,然后停止静注直至动物清醒。B组在输注丙泊酚的同时腹腔内注射可乐定0.5 mg/kg,余和A组相同。分别比较麻醉前、中及苏醒期的NA值(μg/15min)。结果 与基础值相比,A组60 mg·k-1·h-1丙泊酚时的海马NA为(0.13±0.02)μg/15min,B组海马NA为(0.07±0.04)μg/15min,均显著降低(P<0.05)。结论海马α2-NA受体激动药可乐定与丙泊酚麻醉深度的加深有关,但是否是丙泊酚麻醉的共有机制还有待于深入研究。     

Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats

Background. In cerebral ischaemia, hyperglycaemia brings aboutsevere lactate accumulation and neuronal damage when comparedwith normoglycaemia. Propofol has been known to suppress glucosemetabolism in the brain and possess neuroprotective propertiesin cerebral ischaemia. Therefore, in this study we examinedif propofol could attenuate lactate accumulation and neuronaldamage in cerebral ischaemia under hyperglycaemic conditions. Methods. Ten male wistar rats were divided into two experimentalgroups: low-dose (     

Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats

BACKGROUND AND OBJECTIVE: Sevoflurane and propofol reduce the extent of necrosis and improve neurological outcome in rodent models of cerebral ischaemia and reperfusion. However, the effects of these anaesthetics on programmed cell death (apoptosis) are unclear. The present study investigates whether sevoflurane and propofol affect the expression of apoptosis-regulating proteins after cerebral ischaemia in rats. METHODS: Thirty-two fasted male Sprague-Dawley rats were tracheally intubated and the lungs were ventilated (isoflurane and N2O/O2 anaesthesia). After surgical preparation, the animals were randomly assigned to one of the following groups: control (n = 8): fentanyl intravenous (10 microg kg(-1) bolus and 25 microg kg(-1) h(-1) infusion) with N2O/O2; sevoflurane (n = 8): 2.0% sevoflurane (end-tidal concentration) and O2/air; propofol (n = 8): 0.8-1.0 mg kg(-1) min(-1) propofol intravenous and O2/air; sham-operated (n = 8): 25 microg kg(-1) h(-1) fentanyl intravenous and N2O/O2, no cerebral ischaemia. Ischaemia (30 min) was induced by unilateral common carotid artery occlusion plus haemorrhagic hypotension to a mean arterial pressure of 30-35 mmHg. Four hours after cerebral ischaemia the brains were removed and the expression of apoptosis-regulating proteins (Bax, Bcl-2, p53, Mdm-2) was determined using immunofluorescence and Western-blot analyses. RESULTS: The expression of the pro-apoptotic protein Bax was greater in control animals than in sevoflurane or propofol anaesthetized rats and than in sham-operated animals. The concentrations of Bcl-2, p53 and Mdm-2 were not changed 4 h after cerebral ischaemia. CONCLUSIONS: In addition to the anti-necrotic effects of sevoflurane and propofol, these anaesthetics also reduce the concentration of the apoptosis-inducing protein Bax as early as 4 h after ischaemia.     

利多卡因对短暂脑缺血后海马区细胞凋亡的影响

目的 探讨利多卡因对短暂脑缺血后海马区迟发性神经元降解的影响。方法 脑缺血模型为兔脑四血管夹闭模型,２５只家兔随机分成三组：假手术组（Ｓｈ,ｎ＝５）;缺血组（Ｉｓ,ｎ＝１０）,夹闭双侧颈总动脉和椎动脉５ｍｉｎ后恢复脑灌注;利多卡因组（Ｌｉ,ｎ＝１０）,夹闭颈总和椎动脉前５ｍｉｎ给予利多卡因１０ｍｇ／ｋｇ。３组均于３ｄ后取脑行病理ＨＥ染色和ＴＵＮＥＬ染色,对民区阳性细胞进行计数。结果 ＨＥ染色发生缺     

Effects of halothane on arrhythmias induced by myocardial ischaemia

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20–25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dt_max and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.     

短暂性脑缺血-再灌注损伤对老年大鼠海马AQP4及Caspase-3蛋白表达的影响

目的探讨短暂性脑缺血-再灌注损伤对老年大鼠海马AQP4及Caspase-3蛋白表达的影响。方法健康老年Wistar大鼠80只按Pusinelli方法建立四动脉阻断法全脑缺血模型,随机分为脑缺血1min组（Ⅰ组）、脑缺血3min组（Ⅱ组）、脑缺血5min组（Ⅲ组）和假手术组（Ⅳ组）,每组20只。每组又按再灌注时间分为再灌注12h和1、2、3和7d五个亚组,每个亚组4只。应用组织病理学染色观察神经元微观结构,免疫组化方法观察AQP4及Caspase-3蛋白的表达。结果Ⅰ及Ⅱ组各再灌注时点AQP4表达与Ⅳ组比较差异无统计学意义,Ⅲ组各再灌注时点AQP4表达与Ⅳ组比较差异有统计学意义（P〈0．05）。Ⅳ组及Ⅰ组有少量Caspase-3蛋白的表达,Ⅱ及Ⅲ组海马区Caspase-3蛋白的表达明显增加,与Ⅳ组比较差异有统计学意义（P〈0．05或P〈0．01）。两种蛋白在缺血后再灌注12h即有表达,在第1天达高峰,至第3天开始下降。结论老年大鼠对脑缺血-再灌注损伤的敏感性增加,短暂的脑缺血即可造成AQP4及Caspase-3蛋白表达的增加;再灌注后蛋白表达高峰出现早,持续时间长。     

Loss of somatal neuropeptide y immunoreactivity in the rat hippocampus following transient cerebral ischemia

Adult male Wistar rats were subjected to 20 min of global cerebral ischemia and allowed to survive for 1, 2, 4, or 21 days. The brains were processed for immunocytochemistry and the hippocampal neuropeptide Y (NPY)-immunoreactive (-i) neurons were counted and compared to control values. In order to map out the subregional distribution of ischemic cell loss in the hippocampus, cells were also counted in hematoxylin-eosin (HE)-stained brain sections processed from additional ischemic rats after 21 days survival. Cell counts demonstrated a significant loss of hippocampal NPY-i somata 1-21 days after ischemia. The ischemic loss of somatal NPY-i was in the CAI stratum oriens, the CA1 stratum radiatum, and the CA3(ab) subfield not correlated to hippocampal cell loss. NPY-i fibers were found in all subfields of the hippocampus 1-21 days after ischemia. It is known that the majority (>50%) of hippocampal somatostatin-i (SS) neurons also costore NPY-i and the SS-i neurons in the CA1 and CA3(ab) regions of the hippocampus are preserved following an ischemic insult. The present results showed a 90% ischemic loss of CA1 and CA3 NPY-i somata. Based on these findings, it is concluded that ischemia selectively damaged NPY-i and not SS-i within some surviving hippocampal neurons that co-localized both peptides prior to the ischemia.     

Effects of propofol on cerebral oxygenation and metabolism after head injury

Background. Flow-metabolism coupling is thought to be derangedafter traumatic brain injury, while the effects of propofolon flow-metabolism coupling are controversial. We have useda step increase in target plasma propofol concentration in headinjured patients to explore flow-metabolism coupling in thesepatients. Methods. Ten patients with a moderate to severe head injuryreceived a step increase in propofol target controlled infusionof 2 µg ml^–1. Cerebral tissue gas measurements wererecorded using a multimodal sensor, and regional chemistry wasassessed using microdialysis. Arterial-jugular venous oxygendifferences (AVDO₂) were measured and all patients had corticalfunction monitoring (EEG). Results. The step increase in propofol led to a large increasein EEG burst-suppression ratio (0% (range 0–1.1) to 46.1%(range 0–61.7), P<0.05); however, this did not significantlychange tissue gas levels, tissue chemistry, or AVDO₂. Conclusions. Flow-metabolism coupling remains intact duringa step increase in propofol after traumatic brain injury. TheEEG burst-suppression induced by propofol after traumatic braininjury does not appear to be a useful therapeutic tool in reducingthe level of regional ischaemic burden. Br J Anaesth 2003; 91: 781–6     

The cerebral and systemic kinetics of thiopentone and propofol in halothane anaesthetized sheep

The cerebral and systemic kinetics of intravenous thiopentone (250 mg over 2 minutes, n=5) and propofol (100 mg over 2 minutes, n=6) were determined in sheep anaesthetized with halothane (2.0%) and mechanically ventilated to an end-expired carbon dioxide tension of 40 mmHg. The sheep were previously instrumented with arterial and sagittal sinus (effluent from the brain) blood sampling catheters. Systemic kinetics were inferred from the time-course of the arterial blood concentrations, and cerebral kinetics from the time-course of the arterio-sagittal sinus concentration difference across the brain. Under halothane anaesthesia, the peak arterial concentrations of each drug occurred at the end of the two-minute infusion, and was 42.3 mg/l and 12.3 mg/l for thiopentone and propofol, respectively. Propofol had a significantly larger systemic clearance (3.19 l/min) than thiopentone (0.99 l/min). The brain concentrations of propofol equilibrated more slowly with the arterial concentrations than those of thiopentone. The extraction ratio across the brain near the end of the infusions (1.5 min) were 0.85 and 0.46 respectively. These data were also compared to analogous previously published data for initially conscious sheep. The systemic kinetics of thiopentone were little affected by halothane anaesthesia. For propofol, halothane anaesthesia was associated with a statistically significant reduction in clearance (50% of awake), a slower initial half-life (247% of awake), and the emergence of a second slower half-life in some sheep. The cerebral kinetics of both drugs were subtly altered by halothane anaesthesia.     

Effects of graded suppression of the EEG with propofol on the neurological outcome following incomplete cerebral ischaemia in rats.

We evaluated the relation between dose and response for the neuroprotective effect of propofol in a rat model with incomplete cerebral ischaemia. For clarification of the mechanism of neuroprotection, plasma catecholamines and tumour necrosis factor-alpha levels were measured. Three doses (low, moderate and high-dose) of propofol were tested. These produced, respectively, a low amplitude, slowing and a burst-suppression pattern of electroencephalographic activity. Incomplete cerebral ischaemia was produced by right carotid artery occlusion combined with haemorrhagic hypotension (35 mmHg) for 30 min. Neurological outcome at 72 h post-ischaemia in the high-dose group was significantly better than that in both low-dose and moderate-dose groups. Propofol exhibited a trend in the dose-related attenuation of the increases in plasma adrenaline and noradrenaline during ischaemia. Tumour necrosis factor-alpha increased during and after ischaemia in all groups with no intergroup differences. The results indicate that a burst-suppression dose of propofol provides neuroprotection. The protective effect can not be completely explained by the attenuating effect on circulating catecholamines.     

Effects of target-controlled infusion of propofol on the transient hyperaemic response and carbon dioxide reactivity in the middle cerebral artery

The transient hyperaemic response (THR) of blood flow velocity in the middle cerebral artery (vmca), measured by transcranial Doppler ultrasonography (TCD), can be used to assess cerebral autoregulation. We have studied the effects of propofol administered by target- controlled infusion on vmca, THR and carbon dioxide reactivity. We studied 20 healthy adult patients undergoing elective surgery. A standardized anaesthetic comprising alfentanil 10 micrograms kg-1, propofol via a target-controlled infusor and vecuronium 0.1 mg kg-1 was used in both parts of the study. In the first part, THR tests were performed on 10 subjects while awake and then at an 'induction' target concentration of propofol (the target at which consciousness was lost, mean 6.7 (SD 1.1) micrograms ml-1). In the carbon dioxide study, reactivity was tested in 10 patients while awake and at the 'induction' target concentration of propofol by altering the end-tidal carbon dioxide partial pressure by 1 kPa either side of baseline. Propofol caused a significant decrease in vmca but indices of autoregulation, THR ratio and strength of autoregulation increased significantly. Propofol had no effect on carbon dioxide reactivity. These results suggest that propofol may have a beneficial effect on cerebral haemodynamics.      

The influence of etomidate upon cerebral metabolites after complete brain ischaemia in the rat

The influence of etomidate on post-ischaemic cerebral metabolism was examined in 1-year-old male Wistar rats. Ten rats were randomly allocated to each of three groups. Group 1 animals received etomidate for 60 min without undergoing cerebral ischaemia. In Group 2, there was a 60-min recovery period following 15 min of complete cerebral ischaemia. Etomidate was administered to Group 3 animals after 15 min of ischaemia. At the end of the study period, the brains were frozen in situ using liquid nitrogen. The cortex was then biochemically analysed. Considering glycolysis as well as the citric-acid cycle, the pattern of metabolite changes with etomidate application was almost identical to the pattern of spontaneous recovery. The content of energy-rich phosphates was reduced when Groups 2 and 3 were compared with the non-ischaemia group, indicating previous depletion of energy reserves of brain tissue. However, the energy charge as a parameter of energy balance had already been returned to normal values. We conclude that post-ischaemic application of etomidate has no favourable effect on recovery after complete cerebral ischaemia in the rat.     

丙泊酚对大鼠局灶性脑缺血-再灌注时脑组织热休克蛋白70基因和蛋白表达的影响

目的观察丙泊酚对大鼠局灶性脑缺血-再灌注时脑组织热休克蛋白(HSP)70 mRNA和HSP70蛋白表达的影响,以探讨其脑保护的机制。方法采用大脑中动脉线栓法建立大鼠局灶性脑缺血-再灌注模型。60只雄性Wistar大鼠,随机分为假手术组(Sham组)、缺血-再灌注组(I-R组)和丙泊酚组(P组),每组20只。大鼠脑缺血2 h,然后进行再灌注。在再灌注3、6、24、72 h断头取脑组织,采用原位杂交法和免疫组织化学染色检测大鼠脑组织HSP70 mRNA和HSP70蛋白的表达。结果局灶性脑缺血-再灌注后,HSP70 mRNA和HSP70蛋白的表达增加(P<0.01),但HSP70 mRNA表达较早,分布范围较广泛,而HSP70蛋白表达以半暗带区为主。应用丙泊酚能显著地促进脑缺血-再灌注后脑组织中HSP70 mRNA和HSP70蛋白的表达(P<0.01),与脑缺血-再灌注组相比较,HSP70 mRNA和HSP70蛋白不仅表达增多、范围增加,而且还能延缓下降(P<0.05)。结论丙泊酚能促进大鼠局灶性脑缺血-再灌注时HSP70的表达,这可能是其脑保护作用的部分机制。     

Effect of spinal morphine after long-term potentiation of wide dynamic range neurones in the rat

BACKGROUND: Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity. METHODS: Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning. RESULTS: The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation. CONCLUSIONS: Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.     

Superoxide dismutase does not prevent delayed hypoperfusion after incomplete cerebral ischaemia in the rat

Summary Local cerebral blood flow (1CBF) was measured autoradiographically 60 minutes after 15 minutes of forebrain ischaemia in rats treated with superoxide dismutase (SOD) before (50 mg · kg^–1 body weight) or at the end of the ischaemia period (4mg·kg^–1 body weight). Incomplete forebrain ischaemia was produced by a combination of common carotid artery occlusion and bleeding to a mean arterial blood pressure of 50 mmHg. During ischaemia the 1CBF values in cortical areas were less than 3% of the preischaemic values and treatment with SOD prior to ischaemia did not influence 1CBF during ischaemia. Sixty minutes after termination of cerebral ischaemia the 1CBF values were decreased to between 40 and 60% of values found in control animals. Neither form of treatment improved the postischaemic cerebral blood flows. The results imply that postischaemic flow disturbances in the brain may not be due to extracellular superoxide production.