Cerebrovascular reactivity in patients with ruptured intracranial aneurysms

The cerebral vasomotor reactivity to arterial hypotension and hypocapnia was studied in 34 patients between the 3rd and 13th day after rupture of an intracranial saccular aneurysm. Using the intra-arterial xenon-133 injection method, regional cerebral blood flow (rCBF) and cerebral metabolic rate of oxygen (CMRO2) were measured. The intraventricular pressure and cerebrospinal fluid (CSF) lactate and pH levels were determined. The degree of vasospasm was measured on angiograms taken immediately following the rCBF study. The patients were graded clinically according to the system of Hunt and Hess. Cerebral autoregulation was intact in patients in good clinical condition, but was impaired in patients in poor clinical condition. There was a close correlation between the degree of vasospasm and the degree of autoregulatory impairment, which varied from focal disturbances to global impairment. Intracranial hypertension and CSF lactic acidosis were commonly found in association with vasoparalysis. Cerebrovascular response to hyperventilation was generally preserved, although often reduced. During hyperventilation, the cerebral perfusion pressure became elevated, and increases in CMRO2 were often found, even in patients with severe diffuse spasm and cerebral ischemia. The clinical significance of the results in relation to the treatment of delayed cerebral ischemia and to the use of intraoperative induced hypotension is discussed.     

Treatment of subarachnoid hemorrhage with sodium nitroprusside and phenylephrine: an experimental study.

The effectiveness of simultaneous intravenous sodium nitroprusside and phenylephrine in improving the cerebrovascular disturbances and survival rate after induced subarachnoid hemorrhage (SAH) was studied in the cynomolgus monkey. We measured regional cerebral blood flow (rCBF) using the intra-arterial xenon-133 clearance technique. In our experimental animal model, SAH was associated with a persistent reduction in rCBF, elevation of cerebrovascular resistance (CVR), cerebral vasospasm for the duration of the study (150 minutes), and poor survival. For animals receiving the treatment regime (administered approximately 25 minutes after the induced SAH), rCBF remained low, CVR was high, and cerebral vasospasm was persistent. Survival in this group was the same as that observed for the untreated animals. Simultaneous administration of sodium nitroprusside and phenylephrine was ineffective in improving rCBF, CVR, cerebral vasospasm, or survival after SAH. In the control group (receiving only the treatment and not an intracranial insult), rCBF was below resting levels both during and after therapy, indicating impaired cerebral autoregulation. (Neurosurgery, 5: 688--595, 1979).     

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.     

The effect of mannitol on cerebral blood flow

The objective of this study was to evaluate the effects of mannitol, given over different time periods, on regional cerebral blood flow (rCBF) in patients with intracranial aneurysms. Seven patients with unruptured aneurysms (Group I) and 16 patients with Grade I and II subarachnoid hemorrhage (SAH) (Group II) received 1.5 gm/kg/8 hrs of 20% mannitol intravenously over a 24-hour period. Seven other patients with unruptured aneurysms (Group III) received 1.5 gm/kg of mannitol over 8 hours only. The last seven patients with unruptured aneurysms (Group IV) received the same dose, but as an intravenous bolus. Over a period of 24 hours, the patients underwent serial measurements of rCBF, intracranial pressure (ICP), mean blood pressure (MBP), cardiac output, and cerebral metabolic rate of oxygen consumption (CMRO2). Mannitol, when given as a continuous intravenous infusion, increased rCBF significantly without increasing MBP or decreasing ICP. This increase was more pronounced in SAH patients. The effects of mannitol lasted for 18 hours when given over an 8-hour period only; however, when it was given as a bolus, the increase in rCBF lasted for 24 hours, cardiac output tended to increase, and the effect on CMRO2 was variable.     

Cerebral arterial responses to induced hypertension following subarachnoid hemorrhage in the monkey.

Regional cerebral blood flow (rCBF), angiographic cerebral arterial caliber, and cerebrospinal fluid (CSF) pressure were measured in rhesus monkeys to determine the effect of experimentally induced subarachnoid hemorrhage (SAH) on cerebral arterial responses to graded increases in blood pressure. These measurements were also performed in a control group of monkeys subjected to a mock SAH by injection of artificial CSF into the cerebral space. Before subarachnoid injection of blood or artificial CSF, graded increases in mean arterial blood pressure (MABP) to a level 40% to 50% above baseline values had no effect on rCBF. The major cerebral arteries constricted and CSF pressure remained unchanged. Similar responses were observed after injections of artificial CSF. When MABP was increased in animals that had been subjected to subarachnoid injection of blood, rCBF increased and was associated with dilatation of the major cerebral arteries and moderate increases in CSF pressure. These results demonstrate that cerebral arterial responses to increases in blood pressure may be abnormal in the presence of subarachnoid blood. The manner in which abnormal cerebral arterial reactivity, changes in blood pressure, and vasospasm combine to determine the level of cerebral perfusion following SAH is postulated.     

Effect of normal saline bolus on cerebral blood flow in regions with low baseline flow in patients with vasospasm following subarachnoid hemorrhage

OBJECT: Arterial vasospasm is the most common cause of delayed ischemic neurological deficits (DINDs) and one of the major causes of disability following subarachnoid hemorrhage (SAH). Current management of vasospasm involves intravascular volume expansion and hemodynamic augmentation with the goal of increasing cerebral blood flow (CBF). The purpose of this study was to examine the effects of volume expansion on regional (r)CBF in patients with DIND following SAH. METHODS: The authors measured quantitative rCBF on positron emission tomography (PET) scans in six patients with aneurysmal SAH who had developed clinical signs of vasospasm. All patients were kept in a euvolemic state prior to the onset of vasospasm. At the onset of vasospasm, global and rCBF were measured before and after the administration of a normal saline bolus of 15 ml/kg administered over 1 hour. Two patients then received saline infusions of 5 ml/kg x hr over the following 2 to 3 hours and underwent hourly serial CBF measurements. Global and rCBF data were calculated in each patient. The mean rCBF in areas with low flow at baseline (< or = 25 ml/[100 g x min]) increased from 19.1 +/- 3.0 to 29.9 +/- 9.7 ml/(100 g x min) (p = 0.02) with volume expansion. This change was sustained over the following 2 to 3 hours. Pulmonary capillary wedge pressure, mean arterial blood pressure, cardiac output, and central venous pressure did not change significantly during this intervention. CONCLUSIONS: In euvolemic patients with vasospasm, intravascular volume expansion with a normal saline bolus raised CBF in regions of the brain most vulnerable to ischemia.     

Regional cerebral blood flow monitoring in the diagnosis of delayed ischemia following aneurysmal subarachnoid hemorrhage

OBJECT: The goal of this study was to evaluate regional cerebral blood flow (rCBF) monitoring, performed using thermal-diffusion (TD) flowmetry, as a novel means for the bedside diagnosis of symptomatic vasospasm. METHODS: Fourteen patients with high-grade subarachnoid hemorrhage (SAH) who underwent early clip placement for anterior circulation aneurysms were prospectively entered into the study. Thermal-diffusion microprobes were implanted into the white matter of vascular territories that were deemed at risk for developing symptomatic vasospasm. Data on arterial blood pressure, intracranial pressure, cerebral perfusion pressure, rCBF measurement obtained using a TD probe (TD-rCBF), cerebrovascular resistance (CVR), and blood flow velocities were collected at the patient's bedside. The diagnosis of symptomatic vasospasm was based on the manifestation of a delayed ischemic neurological deficit and/or a reduced territorial level of CBF as assessed using stable Xe-enhanced computerized tomography (CT) scanning in combination with vasospasm demonstrated by angiography. Bedside monitoring of TD-rCBF and CVR allowed the detection of symptomatic vasospasm. In the 10 patients with vasospasm the TD-rCBF decreased from 21 +/- 4 to 9 +/- 1 ml/100 g/min (mean +/- standard error of the mean), whereas in the four other patients the TD-rCBF value remained unchanged (mean TD-rCBF = 25 +/- 4 compared with 21 +/- 4 m/100 g/min). A comparison of the results of TD-rCBF and Xe-enhanced CT studies, as well as the calculation of sensitivities, specificities, predictive values, and likelihood ratios, identified a TD-rCBF value of 15 ml/100 g/min as a reliable cutoff for the diagnosis of symptomatic vasospasm. In addition, TD flowmetry was characterized by a more favorable diagnostic reliability than transcranial Doppler ultrasonography. CONCLUSIONS: Thermal-diffusion flowmetry represents a promising method for the bedside monitoring of patients with SAH to detect symptomatic vasospasm. This is of major clinical interest for patients with high-grade SAH, who often cannot be assessed neurologically.     

Posttraumatic cerebral arterial spasm: transcranial Doppler ultrasound, cerebral blood flow, and angiographic findings.

Thirty patients admitted after suffering closed head injuries, with Glasgow Coma Scale scores ranging from 3 to 15, were evaluated with transcranial Doppler ultrasound monitoring. Blood flow velocity was determined in the middle cerebral artery (MCA) and the intracranial portion of the internal carotid artery (ICA) in all patients. Because proximal flow in the extracranial ICA declines in velocity when arterial narrowing becomes hemodynamically significant, the extracranial ICA velocity was concurrently monitored in 19 patients. To assess cerebral perfusion, cerebral blood flow (CBF) measurements obtained with the intravenous 133Xe technique were completed in 16 patients. Vasospasm, designated as MCA velocity exceeding 120 cm/sec, was found in eight patients (26.7%). Severe vasospasm, defined as MCA velocity greater than 200 cm/sec, occurred in three patients, and was confirmed by angiography in all three. Subarachnoid hemorrhage (SAH) was documented by computerized tomography in five (62.5%) of the eight patients with vasospasm. All cases of severe vasospasm were associated with subarachnoid blood. The time course of vasospasm in patients with traumatic SAH was similar to that found in patients with aneurysmal SAH; in contrast, arterial spasm not associated with SAH demonstrated an uncharacteristically short duration (mean 1.25 days), suggesting that this may be a different type of spasm. A significant correlation (p less than 0.05) was identified between the lowest CBF and highest MCA velocity in patients during the period of vasospasm, indicating that arterial narrowing can lead to impaired CBF. Ischemic brain damage was found in one patient who had evidence of cerebral infarction in the territories supplied by the arteries affected by spasm. These findings demonstrate that delayed cerebral arterial spasm is a frequent complication of closed head injury and that the severity of spasm is, in some cases, comparable to that seen in aneurysmal SAH. This experience suggests that vasospasm is an important secondary posttraumatic insult that is potentially treatable.     

The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs

Summary We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p<0.05) and Hood velocity (48% of control, p<0.05), with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1–0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.     

Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Relationship between cerebral blood flow and oxygen metabolism, and extracellular glucose and lactate concentrations during middle cerebral artery occlusion and reperfusion: a microdialysis and positron emission tomography study in nonhuman primates

OBJECT: Changes in lactate and glucose levels in the brain may be used to monitor a dynamic ischemic process. The authors related extracellular concentrations of glucose and lactate to regional cerebral blood flow (rCBF) and cerebral metabolic rate of oxygen (CMRO2) in a model of ischemia. METHODS: Transient (2 hours) middle cerebral artery occlusion (MCAO) was performed in eight macaque monkeys. Extracellular measurements of glucose and lactate levels using microdialysis (two probes in each brain) and sequential positron emission tomography measurements were performed during MCAO and reperfusion. Glucose and lactate levels were related to rCBF and CMRO2 as well as the pathophysiological categories of severe ischemia and penumbra. In probe regions characterized by severe ischemia, there were significant changes in glucose and lactate levels and the lactate/glucose ratio. In probe regions distinguished by penumbra, only lactate levels increased significantly and, in general, the changes were smaller and transient. This difference between severe ischemic and penumbral regions was significant for all microdialysis parameters. There was a significant correlation between glucose, and CBF and CMRO2. Lactate concentration was correlated with CMRO2. CONCLUSIONS: Extracellular glucose levels might be limited by rCBF, whereas lactate levels were more related to CMRO2. Lactate concentration is a better marker of irreversible ischemia than glucose concentration, although near-zero levels of glucose during MCAO probably signals near-complete cessation of rCBF. In situations with elevated lactate levels, glucose may help to discriminate between partial and severe ischemia.     

Flumazenil reversal of midazolam in dogs: dose-related changes in cerebral blood flow, metabolism, EEG, and CSF pressure

Large doses of flumazenil, given rapidly (over 5-10 s), are reported to elevate cerebral blood flow (CBF) and intracranial pressure to supranormal values when given to dogs receiving midazolam. This study examined the cerebral effects of giving smaller, graduated doses of flumazenil (0.0025, 0.01, 0.04, and 0.16 mg/kg), slowly (over 60 s), to dogs receiving midazolam and to dogs not receiving midazolam both when cerebrospinal fluid (CSF) pressure was normal and when CSF pressure was elevated (intracranial balloon) to about 30 mm Hg. In dogs with normal CSF pressure that were receiving midazolam, the effects of flumazenil were as follows: (a) low doses of flumazenil caused reversal of the reduction in cerebral metabolic rate for oxygen (CMRO2) and activity of the electroencephalogram produced by midazolam, (b) moderate doses of flumazenil produced a decrease of cerebral vascular resistance, and an increase of CBF and CSF pressure that did not significantly change cerebral perfusion pressure (CPP), and (c) the highest dose of flumazenil increased CBF to supranormal values. All of these flumazenil effects "peaked" at 3-6 min, with values returning to pre-flumazenil levels by 15-30 min. Flumazenil caused no such changes in dogs with elevated CSF pressure that were receiving midazolam or in dogs that were not receiving midazolam. The results are consistent with a specific, doserelated benzodiazepineantagonist action of flumazenil. Lack of flumazenil effect at elevated CSF pressure may reflect reversible changes in cerebral structure, metabolism, or benzodiazepine receptors produced by the intracranial balloon and elevation of CSF pressure. The doses of flumazenil used here to reverse the cerebral effects of midazolam appear unlikely to produce adverse effects because increase of CMRO2 was matched by increase of CBF, the mean increase of CSF pressure was modest (+9 +/- 3 mm Hg, mean +/- SEM), and CPP was unchanged.     

Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: investigation of the possible role of xanthine oxidase in chronic vasospasm

Based on accumulating evidence of the role of xanthine oxidase (XO) in generating oxygen free radicals and causing tissue damage during ischemia, we examined the possible role of XO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). After inducing SAH in dogs by two autologous blood injections 2 days apart, chronic vasospasm of the basilar artery was reliably produced. There was a 3.5-fold elevation in uric acid (UA), the product of XO, in the cerebrospinal fluid (CSF) of these animals. Parenteral administration of allopurinol (i.v., 25 mg/kg, every 6 hours), a specific blocker of XO, successfully abolished the elevation in CSF uric acid levels due to SAH. However, angiographic vasospasm measured on Day 7, morphological changes observed by electron microscope, and elevated CSF prostaglandin levels were not altered by the treatment. It can be concluded that the observed activation of the enzyme XO, which is a well-known source of oxygen free radicals in ischemia in various organs, is not playing a major role in the pathogenesis of chronic cerebral vasospasm in this animal.     

Effects of subarachnoid hemorrhage and a thromboxane A2 synthetase inhibitor on intracranial prostaglandins

The effects of subarachnoid hemorrhage (SAH) on intracranial prostaglandins (PGs) were studied in canines. Subarachnoid hemorrhage was produced by the "two hemorrhage" method. Basilar artery caliber and regional cerebral blood flow (rCBF) in the occipital cortex were reduced by 42% and 43% during delayed vasospasm, respectively. Once delayed vasospasm had developed, intravenous infusion of OKY-046, a selective inhibitor of thromboxane (TX) A2 synthetase, induced no significant change in angiographic vasospasm but caused a significant increase in rCBF. In delayed vasospasm, cortical levels of PGF2 alpha were significantly decreased, whereas plasma levels of PGF2 alpha and TXB2 in the transverse sinus were significantly increased. The intravenous infusion of OKY-046 in delayed vasospasm induced a significant increase in cortical PGF2 alpha and PGE in the occipital cortex, and caused a significant increase in plasma 6-keto-PGF1 alpha and a significant decrease in plasma TXB2 in the transverse sinus. In delayed vasospasm, decreased cortical levels of PGF2 alpha may reflect a decrease in rCBF and increased plasma PGF2 alpha and TXB2 levels may reflect enhancement of intravascular coagulation. These PGs have very strong and various biological activities. The results suggest that SAH induces complicated changes of intracranial PGs and OKY-046 can improve these pathological changes.     

Hemodynamic and metabolic effects of cerebral revascularization

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.     

Nitric oxide metabolites in cisternal CSF correlate with cerebral vasospasm in patients with a subarachnoid haemorrhage

Summary.  Background: The pathogenesis of cerebral vasospasm is likely to be multifactorial. Exposure of the adventitia of large cerebral arteries to blood breakdown products initiates a cascade of changes in both morphology and vasomotor regulation of the exposed vessels. The role of nitric oxide (NO) in development of cerebral vasospasm process is controversial. Basal cerebral vascular tone requires the continuous release of NO, nevertheless NO is involved in free radical mediated injury of endothelial cell membrane. Concentrations of nitrate/nitrite (stabile endproducts of NO metabolism) were studied in cisternal cerebrospinal fluid (cCSF) in patients suffering from aneurysmal subarachnoid haemorrhage (SAH).  Method: 21 patients suffering from aneurysmal SAH were investigated. Treatment included aneurysm clipping, cisternal drainage of CSF and intravenous nimodipine in all patients as well as tripple H therapy when indicated. TCDS was performed on a daily basis. A mean flow velocity of more than 150 cm/sec and the development a delayed neurological deficit was defined as vasospasm. CSF samples were collected on the day of surgery and for the 7 days following. NO-M (nitrite and nitrate) were measured using a commercially available test kit.  Findings: 5 of 21 patients developed clinically symptomatic vasospasm. There was a significant difference in NO levels between the groups. Patients with cerebral vasospasm showed significantly higher levels of NO-M in CSF than patients with a uncomplicated follow-up between day 2 and 8.  Interpretation: Our preliminary results indicate that SAH leads to an increase in NO-M in CSF. This increase of NO-M significantly correlates with the flow velocities in TCDS measurement suggesting that NO plays an important role in the pathogenesis of cerebral vasospasm. Published online April 28, 2003  Correspondence: A. Woszczyk, Department of Neurosurgery, Justus-Liebig University, Klinikstro?e 29, 35292 Giessen, Germany.     

Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

OBJECT: Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be evoked by the decreased availability of nitric oxide (NO). Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO synthase (NOS), have been associated with the course and degree of cerebral vasospasm in a primate model of SAH. In this study, the authors sought to determine if similar changes in CSF ADMA levels are observed in patients with SAH, and whether these changes are associated with NO and NOS metabolite levels in the CSF and the presence of cerebral vasospasm. METHODS: Asymmetric dimethyl-L-arginine, L-arginine, L-citrulline, and nitrite levels were measured in CSF and serum samples collected during the 21-day period after a single aneurysmal SAH in 18 consecutive patients. Samples were also obtained in a control group consisting of seven patients with Chiari malformation Type I and five patients with spontaneous intracerebral hemorrhage without SAH. Vasospasm, defined as a greater than 11% reduction in the anterior circulation vessel diameter ratio compared with the ratio calculated from the initial arteriogram, was assessed on cerebral arteriography performed around Day 7. RESULTS: In 13 patients with SAH, arteriographic cerebral vasospasm developed. Cerebrospinal fluid ADMA levels in patients with SAH were higher than in those in the control group (p < 0.001). The CSF ADMA level remained unchanged in the five patients with SAH without vasospasm, but was significantly increased in patients with vasospasm after Day 3 (6.2 +/- 1.7 microM) peaking during Days 7 through 9 (13.3 +/- 6.7 microM; p < 0.001) and then gradually decreasing between Days 12 and 21 (8.8 +/- 3.2 microM; p < 0.05). Nitrite levels in the CSF were lower in patients with vasospasm compared to patients without vasospasm (p < 0.03). Cerebrospinal fluid ADMA levels positively correlated with the degree of vasospasm (correlation coefficient [CC] = 0.88, p = 0.0001; 95% confidence interval [CI] 0.74-0.95) and negatively correlated with CSF nitrite levels (CC = -0.55; p = 0.017; 95% CI -0.81 to -0.12). CONCLUSIONS: These results support the hypothesis that ADMA is involved in the progression of cerebral vasospasm. Asymmetric dimethyl-L-arginine and its metabolizing enzymes may be a future target for treatment of cerebral vasospasm after SAH.     

大鼠脑血管痉挛时血及脑组织NO、内皮素改变和银杏叶制剂的作用

目的　探讨 Ｎ Ｏ、内皮素（ Ｅ Ｔ） 与蛛网膜下腔出血（ Ｓ Ａ Ｈ） 后脑血管痉挛（ Ｃ Ｖ Ｓ） 的关系和银杏叶制剂（ Ｇ Ｂ Ｅ） 的防治作用。方法　对假手术组、单纯 Ｓ Ａ Ｈ 模型组和 Ｇ Ｂ Ｅ 处理组大鼠检测２４ 小时内局部脑血流量、血及脑组织 Ｎ Ｏ、 Ｅ Ｔ 含量,并测基底动脉管径及行海马病理检查。结果　 Ｓ Ａ Ｈ 造成局部脑血流量持续下降,并有基底动脉痉挛,海马 Ｃ Ａ１ 区神经元明显受损;血 Ｎ Ｏ 减少、 Ｅ Ｔ 增多,脑组织 Ｎ Ｏ、 Ｅ Ｔ 均增加; Ｇ Ｂ Ｅ 使上述改变均减轻。结论　血 Ｎ Ｏ 减少、 Ｅ Ｔ 增多促使 Ｓ Ａ Ｈ 后 Ｃ Ｖ Ｓ 发生,脑组织 Ｎ Ｏ 和 Ｅ Ｔ 增加加重脑损伤; Ｇ Ｂ Ｅ 通过逆转 Ｎ Ｏ、 Ｅ Ｔ 异常改变而发挥保护作用。     

Effects of hyperbaric oxygenation

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.     

Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.