Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats

We evaluated the effect of hyperbaric oxygen (HBO) therapy on neurological function and infarct size in 33 unanesthetized cats subjected to temporary 6-hour or 24-hour occlusion of the middle cerebral artery (MCA) 7 to 10 days after transorbital implantation of a vessel occluder. HBO therapy (100% oxygen at 1.5 atmospheres absolute) was administered for 40 minutes during or after 6-hour occlusions and before, during, and after 24-hour occlusions. Neurological function was graded on a scale of 0 to 10 every 30 minutes before, during, and after occlusion and HBO treatments until it stabilized and then daily until the cats were killed 10 days after occlusion. The results were compared with observations in 13 untreated controls and 6 cats that received 100% O2 at atmospheric pressure during a 6-hour MCA occlusion. HBO therapy during the 1st or 3rd hour of a 6-hour MCA occlusion resulted in a four-grade improvement of the initial neurological function; this effect persisted during the remainder of the occlusion. The average grade of neurological deficit at death was 94% less than in the untreated cats (P less than 0.03). Infarct size in the HBO-treated group was 58% less than in controls (P less than 0.03). There was no significant difference in infarct size between the untreated cats and those treated with 100% O2 at atmospheric pressure. HBO therapy during the 4th hour of a 6-hour MCA occlusion had no statistically significant effect on infarct size, even though the mean neurological deficit was 73% less than in controls (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of mannitol on cerebral blood flow and microcirculation during experimental middle cerebral artery occlusion

Regional cerebral blood flow (rCBF) was measured during and after a 2-3 hour occlusion period of the middle cerebral artery (MCA) in cats with the hydrogen clearance technique. The effects of mannitol upon rCBF were studied. Transient hypotension during occlusion dropped the blood flow to near zero on the occluded side, leading to postischemic hypoperfusion. Mannitol failed to modify blood flow during the occlusion period, but was effective in preventing any further decrease of blood flow during hypotension. Animals receiving mannitol had an improved postischemic recovery of blood flow. The correlation of ischemic severity and postischemic brain damage and the effects of mannitol on these parameters are discussed.     

Comparison of the effect of fluosol DA and dextran 40 on regional cerebral blood flow, infarction size, and mortality in cats with temporary occlusion of the middle cerebral artery

Twenty-four cats were divided into two groups and treated with an intravenous infusion of either fluosol DA or dextran. One-half of the animals in each group were ventilated with room air and one-half with 100% oxygen. The right middle cerebral artery was occluded for a period of 4 hours through a transorbital approach. Regional blood flow by the hydrogen clearance method was measured before and after the infusion of fluosol DA or dextran, after oxygenation in the animals on 100% oxygen, three times during the period of ischemia, and after reperfusion. Regional cerebral blood flow increased slightly with the infusion of fluosol or dextran, decreased slightly with hyperoxygenation in the animals so treated, and decreased markedly in the right hemisphere during temporary occlusion of the right middle cerebral artery in all groups. With reperfusion regional flows in the right hemisphere varied considerably, with some animals showing hyperperfusion and others essentially no flow. There was no significant difference in average regional cerebral blood flow between any of the groups. The severity of infarction in all groups was directly related to the decrease in regional cerebral blood flow in the right hemisphere during temporary occlusion. There was also a strong correlation between the regional cerebral blood flow in the right hemisphere after reperfusion and the severity of infarction. In general, the animals showing normal or increased flow after reperfusion had small infarcts and those showing no reflow had large infarcts. Mortality was high in all groups, was not significantly different between any of the groups, and was highly correlated to the size of infarction. In brief, in this study fluosol offered no advantage over dextran, and probably neither agent, in the dose used, offered any protection against cerebral ischemia.     

Somatosensory evoked potential monitoring of temporary middle cerebral artery occlusion during aneurysm operation

Somatosensory evoked potentials (SEPs) in response to median nerve stimulation were used as a guide to cortical function during temporary occlusion of the distal M1 segment of the middle cerebral artery (MCA) in the surgical treatment of five large aneurysms of the MCA bifurcation. MCA occlusion times ranged from 8 to 19 minutes under moderate hypothermia at 28.8 degrees to 30.3 degrees C. SEPs were preserved for variable times during MCA occlusion, ranging from no increase in latency after 13 minutes of occlusion to severe deterioration after 6 minutes. In no case was MCA occlusion maintained for longer than 3 minutes in the presence of a severely disturbed SEP. Recovery of the SEP to its preoperative relationship with that of the nonoperated hemisphere was seen in all cases before the end of operation. All patients were awake after rewarming at the end of operation without any neurological deficit. Monitoring the SEP pertaining to the territory of a cerebral artery during its temporary occlusion can help avoid ischemic damage and will allow the surgeon to take advantage of the several benefits of this technique in aneurysm surgery.     

Computerized cortical surface electroencephalography after temporary middle cerebral artery occlusion in rabbits

The sensitivity and regional specificity of intraoperative electroencephalographic (EEG) monitoring in cerebral ischemia was evaluated in a new experimental model of temporary focal cerebral ischemia in rabbits. EEG potentials were recorded directly from the cortical surface using a bipolar disc electrode grid and were analyzed by computer. Groups of 5 animals each underwent temporary occlusion of the left middle cerebral arterial trunk for 5, 10, 20, 30, 45, or 60 minutes. EEG data were recorded from the cortex proximal (temporal site) and distal (parasagittal site) to the middle cerebral arterial trunk during occlusion and 2 hours of reperfusion. EEG suppression was detected immediately after occlusion at the temporal site by analysis of power spectra in 29 of 30 rabbits (mean power, 32% of base line), by compressed spectral array (CSA) edge analysis in 23, and by analysis of the conventional EEG wave form in 24. Within 5 minutes after the start of occlusion, all 30 rabbits showed EEG power suppression and 26 showed decrease in the CSA edge frequency or in the routine EEG wave form. By the end of the occlusion period, EEG power at the temporal site had decreased to 20.5% of base line. At the parasagittal site, a lesser degree of EEG suppression was detected; 20 rabbits had an initial loss of EEG power (mean, 85.7% of base line), 13 had decrease in the CSA edge, and 7 had suppression of the EEG wave form. By the end of the occlusion period, spectral power at the parasagittal site had decreased in 25 of 30 rabbits to a mean of 86.9% of base line.(ABSTRACT TRUNCATED AT 250 WORDS)     

SEM evaluation of endothelial damage following temporary middle cerebral artery occlusion in dogs

Microsurgical clips and tourniquets were used to occlude middle cerebral arteries of dogs for 45-minute periods. Scanning electron microscopy and light microscopy studies revealed significant endothelial damage in many of these arteries. Less traumatic microsurgical clips are needed for temporary small vessel occlusion.     

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats. Effects of anesthesia

Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p less than 0.05). This was noted in densely areas (indomethacin = 84.3%, control = 87.5%), "penumbra" regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p less than 0.05), as was cerebral perfusion (p less than 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p less than 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p less than 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbital-stabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.     

Catecholamine content of cerebral tissue after occlusion or manipulation of middle cerebral artery in cats.

The authors determined by fluorimetry the norepinephrine-epinephrine content (NE-E) of cerebral tissue from 38 cats, to ascertain whether constriction of hypersensitive arterial vessels by vasoactive agents in ischemic cerebral tissue could cause extension of cerebral infarcts and worsening of neurological deficits. Twenty-three cats had the left middle cerebral artery (MCA) occluded transorbitally, and 10 cats had sham operations. Five cats had only the surgical procedures necessary for obtaining tissue; mean NE-E content was 0.30 mug/gm (SD=0.041). For the other 33 cats, including those with sham operations, values were variable, ranging from 0.07 to 0.60 mug/gm. Low values usually were obtained for ischemic hemispheres 24 hours and 7 days after MCA occlusion, but at other times values could be high or low on either side. Many factors unrelated to tissue damage, including arterial manipulation, influence the catecholamine content of cerebral tissue.     

转染血管内皮生长因子基因神经干细胞移植对大鼠脑缺血损伤的修复作用

目的 探讨转染血管内皮生长因子（VEGF）基因神经干细胞移植对大鼠脑缺血损伤的修复作用。方法 建立大鼠大脑中动脉梗塞（tMCAO）模型，将tMCAO模型随机分为对照组、注射磷酸盐缓冲液（PBS液）的PBS液对照组、接受神经干细胞（NSCs）移植的NSCs组、接受转染VEGF基因的NSCs移植的NSCs-VEGF组，采用立体定向法将相应移植物注射到tMCAO模型的右侧纹状体缺血半暗区。各组移植后2、4、6、8、10、12周进行神经功能损害程度（NSS）评分；移植后7d，采用免疫荧光染色法观察NSCs-VEGF组移植细胞的VEGF基因表达情况；12周时，采用免疫荧光染色法追踪NSCs-VEGF组移植细胞向神经元方向分化情况，并同时行各组移植区周围血管内皮细胞半定量计数。结果 移植后2～12周，NSCs-VEG组的NSS评分均低于其它3组，第12周时的NSS评分与其它3组比较，差异有统计学意义（P〈0．01）；移植后7d，NSCs-VEGF组的移植细胞从移植点向周围迁徙，部分表达VEGF基因；移植后12周，NSCs-VEGF组部分移植细胞分化成神经元，其移植区血管内皮细胞数显著高于其它3组（P〈0．05）。结论 转染VEGF基因的神经干细胞移植对脑缺血所致的损伤具有一定的修复作用。     

Changes in local cerebral blood flow,local EEG,and flow in the distal stump of the middle cerebral artery in cats with occlusion of the middle cerebral artery

Summary The local EEG, the local cerebral blood flow (1CBF), and the flow in the distal stump of the occluded middle cerebral artery were simultaneously recorded in 28 acute experiments in cats. Nembutal anaesthesia was used eleven times, and Halothane anaesthesia 17 times.The recordings were made via platinum electrodes: 12 in the ischaemic hemisphere, and 2–3 in the opposite non-ischaemic hemisphere. The flow in the occluded middle cerebral artery was recorded via a platinum electrode introduced into this artery via the transorbital approach. The changes in 1EEG, 1CBF, and middle cerebral artery flow were studied during normotension, hypertension, and hypotension. A beneficial effect of hypertension was noted in the acute phase of brain ischaemia. Hypertension counteracted also the diaschisis in the non-ischaemic part of the ischaemic hemisphere and in the opposite non-ischaemic hemisphere. A correlation between 1EEG changes and 1CBF changes was noted. In addition an interesting discrepancy was observed between the rapid H₂ clearance in the middle cerebral artery stump and the much slower H₂ clearance in the ischaemic brain area.Significant differences between experiments under Halothane and experiments under Nembutal anaesthesia were noted. In the acute phase those changes are probably the result of the different levels of blood pressure in those two groups.     

Brain tolerance to middle cerebral artery occlusion during hypotension in primates

The aim of this study was to determine the duration of middle cerebral artery occlusion required to produce significant ischemic damage when the occlusion occurs during controlled systemic hypotension. In 21 anesthetized cynomolgus monkeys, an IV infusion of sodium nitroprusside was used to lower the mean arterial blood pressure to 45-50 mmHg for 90 minutes. Middle cerebral artery occlusion for 15, 30, 45, or 60 minutes was performed during the hypotensive period. Neurological function was then evaluated every 8 hours for a total of 72 hours. At the end of the observation period, the monkeys were again anesthetized, magnetic resonance imaging was performed, and the brain was perfused with 10% buffered formalin. Neurological deficits were observed after 30 minutes, but not after 15 minutes, of middle cerebral artery occlusion, and rapidly increased in incidence and severity when the duration of occlusion was increased. After 60 minutes of occlusion, all the monkeys exhibited severe deficits. Four monkeys died during the observation period--two in each of the 45- and 60-minute occlusion groups. Histopathological examination revealed that little or no ischemic damage resulted from a 15-minute occlusion during hypotension. However, severe ischemic damage began to occur after only 30 minutes of occlusion, and all monkeys subjected to middle cerebral artery occlusion for 60 minutes developed extensive regions of infarction. The size and incidence of these infarctions correlated well with the lesions observed in the magnetic resonance images. These results demonstrate that the duration of middle cerebral artery occlusion that produces cerebral infarction in primates is drastically reduced when the occlusion occurs at hypotensive levels commonly employed during neurovascular surgical procedures.     

直接抽吸取栓术治疗大脑中动脉M2段闭塞

目的观察直接抽吸取栓术治疗大脑中动脉M2段闭塞的效果。方法回顾性分析8例接受直接抽吸取栓术治疗的大脑中动脉M2段闭塞患者,统计血管再通率及术后24 h颅内出血情况;于术前及术后24 h、14天对患者进行美国国立卫生研究院卒中量表(NIHSS)评分,术后90天统计改良Rankin量表(mRS)评分,以评价预后。结果 8例(100%)血管均成功再通,无需其他取栓器材和技术补救;术后均未发生症状性颅内出血,3例出现无症状性颅内出血。患者术后24 h、术后14天NIHSS评分逐渐下降。术后90天,8例均达到mRS评分≤2分的良好结局,其中7例达到mRS评分≤1分的优良结局。结论直接抽吸取栓术治疗大脑中动脉M2段闭塞可早期改善患者神经功能,有效性和安全性均良好。     

Cerebral oximetry for the detection of cerebral ischemia during temporary carotid artery occlusion

The near-infrared spectroscopy cerebral oximeter was assessed as a monitoring device for detecting and/or predicting cerebral ischemia during carotid endarterectomy (CEA) and the balloon occlusion test in 24 patients, 12 males and 12 females aged 28 to 77 years (mean 59.9 years). Tolerance testing of complete internal carotid artery (ICA) occlusion by balloon inflation for 20 minutes was performed in nine patients (cerebral aneurysm 6, neck tumor 3) and CEA was performed in 15 patients. The probe of the cerebral oximeter was placed on the forehead of the affected side and regional cerebral oxygen saturation (rSO2) was monitored continuously during all procedures. Stump pressure was measured just after ICA occlusion. Collateral circulation detected by digital subtraction angiography was classified into three groups: good, moderate, or poor. Stump pressure was 41-90 mmHg (mean 61.3 mmHg) in the good collateral circulation group, 40-43 mmHg (41.5 mmHg) in the moderate group, and 14-30 mmHg (23.8 mmHg) in the poor group. Change in rSO2 after ICA occlusion was +3.5(-)-4.2% (mean -1.6%) in the good collateral circulation group, -1.2(-)-6.6% (-3.2%) in the moderate group, and -2.4(-)-10.2% (-6.6%) in the poor group. Changes in rSO2 were significantly different between the good and poor collateral circulation groups (p < 0.01). A greater than 5% fall in rSO2 was observed in 0 of 15 patients in the good collateral circulation group, one of five in the moderate group, and three of four in the poor group. The cerebral oximeter is a useful, real-time, non-invasive method to measure brain oxygenation during CEA, skull base surgery, or other procedures which need to evaluate brain ischemia. A fall of greater than 10% from the rSO2 baseline value is dangerous, but less than 5% is safe.     

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)