Effects of elevated ICP on brain function: can the multiparametric monitoring system detect the 'Cushing Response'?

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K+ and H+ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50-60 mmHg for 13-15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50-60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.     

Effects of elevated ICP on brain function: Can the multiparametric monitoring system detect the 'Cushing Response'?

Abstract

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K⁺ and H⁺ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50–60 mmHg for 13–15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50–60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.     

Diagnosis and management of increased intracranial pressure

Increased intracranial pressure (ICP) is a pathological state common to a variety of neurological diseases, all of which are characterized by the addition of volume to the skull contents. Elevated ICP may lead to brain damage or death by two principle mechanisms: 1) global hypoxic-ischemic injury, as a consequence of reduced cerebral perfusion pressure (CPP) and cerebral blood flow; and 2) mechanical distortion and compression of brain tissue as a result of intracranial mass effect and ICP compartmentalization. All ICP therapies have as a goal, reduction of intracranial volume. In unmonitored patients with acute neurological deterioration, head elevation, hyperventilation, and mannitol (1g/kg) can rapidly lower ICP. Fluid-coupled ventricular catheters and fiberoptic transducers are the most accurate and reliable instruments for measuring ICP. In monitored patients, the treatment of critically raised ICP should proceed in an orderly step-wise fashion: 1) consideration of neuroimaging to exclude a new surgically operable lesion; 2) intravenous sedation to attain a quiet motionless state; 3) manipulation of blood pressure to keep CPP >70 and <120; 4) mannitol infusion; 5) moderate hyperventilation (P(CO2) 26 to 30 mmHg); and 6) high-dose pentobarbital therapy. Application of moderate hypothermia (32 to 33 degrees C) shows promise as a newer method for treating refractory ICP. Placement of an ICP monitor is the critical first step in management of ICP. Treatment is best done using a stepwise protocol, with careful attention to sedation and CPP control prior to using mannitol and hyperventilation.     

Auditory nerve-brain stem evoked potentials in cats during manipulation of the cerebral perfusion pressure

In order to study the effects of various degrees of cerebral ischemia on the auditory nerve-brain stem evoked potentials (BAEP), the cerebral perfusion pressure (CPP), defined as the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP), was systemically manipulated in anesthetized, paralyzed and ventilated cats. The CPP was varied by decreasing MAP, either by hemorrhage or by the infusion of a vasodilating drug, and elevating ICP by infusion of mock CSF into the cisterna magna, or by MAP depression and ICP elevation simultaneously. Even though the lower limit of adequate CPP is considered to be 40 mm Hg, the EEG became isoelectric at an average CPP of 24 mm Hg and the BAEP became isoelectric at an average CPP of 7 mm Hg. These extremely low CPP values of 7-24 mm Hg are far below the range of autoregulation of cerebral blood flow (CBF) so that the brain stem auditory pathway is still capable of generating its electrical response (BAEP) at very low CBF. This is paradoxical since these same regions of the brain have been shown to have the highest levels or regional metabolism as shown by their very high local cerebral blood flow and local glucose utilization.     

Effect of systemic arterial blood pressure on cerebral blood flow in intracranial hypertension.

In five baboons and 11 cats cerebral ischaemia was produced either by inflating an epidural balloon and or by ligating major arteries supplying the brain. Fifteen of the animals developed intracranial hypertension after cerebral ischaemia. If ICP were high, but still significantly lower than MABP, elevation of MABP by noradrenaline infusions was accompanied by a proportional increase of ICP. However, the increase of ICP was lower than that of MABP so that CPP was raised. CBF measured by the 133Xenon clearance technique was significantly increased by arterial hypertension in eight cases. The proportional increase of CPP and CBF by elevation of arterial blood pressure was substantially greater, the lower ICP was immediately after ischaemia. There was no effect of MABP in cases in which ICP equalled MABP.     

Noninvasive study of critical thresholds of intracranial pressure and cerebral perfusion pressure for cerebral circulation and brain function

To ascertain the critical thresholds of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) for cerebral circulation and brain function, the extra- and intracranial haemodynamics and electrical brain responses were evaluated noninvasively with Doppler ultrasonography and multimodality evoked potentials (MEP's) in 50 patients with severe head injury. Both extra- and intracranial blood flow velocities changed monotonically depending on the changes in ICP and CPP. They were decreased when ICP increased to 20-30 mmHg and when CPP decreased to 40-50 mmHg. The changes in elasticity index of the pulse wave of the common carotid artery was proportional to those of blood flow velocities. The frequency and degree of abnormalities of MEP's were proportionally increased with the rise of ICP and reduction of CPP. When ICP increased to higher than 31 mmHg, MEP's were classified as moderately or severely abnormal in more than 76% of the recordings. These results indicate that noninvasive study by use of Doppler ultrasonography and MEP's can provide valuable information on critical brain ischaemia and brain dysfunction in patients with acute intracranial hypertension.     

Noninvasive study of critical thresholds of Intracranial pressure and cerebral perfusion pressure for cerebral circulation and brain function

To ascertain the critical thresholds of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) for cerebral circulation and brain function, the extra- and intracranial haemodynamics and electrical brain responses were evaluated noninvasively with Doppler ultrasonography and multimodality evoked potentials (MEP’s) in 50 patients with severe head injury. Both extra- and intracranial blood flow velocities changed monotonically depending on the changes in ICP and CPP. They were decreased when ICP increased to 20-30 mmHg and when CPP decreased to 40-50 mmHg. The changes in elasticity index of the pulse wave of the common carotid artery was proportional to those of blood flow velocities. The frequency and degree of abnormalities of MEP’s were proportionally increased with the rise of ICP and reduction of CPP. When ICP increased to higher than 31 mmHg, MEP’s were classified as moderately or severely abnormal in more than 76% of the recordings. These results indicate that noninvasive study by use of Doppler ultrasonography and MEP’s can provide valuable information on critical brain ischaemia and brain dysfunction in patients with acute intracranial hypertension.     

The Values of Cerebrovascular Pressure Reactivity and Brain Tissue Oxygen Pressure Reactivity in Experimental Anhepatic Liver Failure

Background

We investigated in a porcine model of anhepatic acute liver failure (ALF), the value of two parameters describing cerebrovascular autoregulatory capacity, pressure reactivity index (PRx) and brain tissue oxygen pressure reactivity (ORx), regarding their power to predict the development of intracranial hypertension.

Methods

In six pigs, hepatectomy was performed. Only one animal was sham operated. All animals received neuromonitoring including arterial blood pressure, intracranial pressure (ICP), and brain tissue partial oxygen pressure (P_brO₂). The average time of neuromonitoring was 31.0 h. Cerebral perfusion pressures (CPP), cerebrovascular pressure reactivity index (PRx) and brain tissue oxygen reactivity index (ORx) were calculated.

Results

Perioperative disturbance of AR improved within 4 h after surgery. From 6 to 16 h post hepatectomy, ICP did slowly increase by 4 mmHg from baseline; CPP remained stable around 40 mmHg. PRx and ORx, however, indicated in this period a progressive loss of AR, reflected in a decrease of P_brO₂ despite unchanged CPP. Beyond 16 h, ICP rose quickly. At CPP levels below 35 mmHg, P_brO₂ fell to ischemic levels.

Conclusions

The loss of cerebrovascular autoregulatory capacity, indicated by a rise of PRx and ORx precedes the final crisis of uncontrollable intracranial hypertension in this animal model by hours. During this phase cerebral blood flow, as reflected in tissue oxygenation, deteriorates despite unchanged CPP. Monitoring of AR during ALF therefore seems to carry the power to identify a risk for development of critical CBF and intracranial hypertension.

     

Prognostic value of ICP, CPP and regional blood flow monitoring in diffuse and focal traumatic cerebral lesions

Forty patients with severe traumatic brain injury (GCS score 8 and less) aged 16-54 years treated in our clinic were analyzed. Correlations between clinical symptoms, CT signs of diffuse and focal traumatic lesions, intracranial hemorrhage, indices of cerebral blood flow (CBF) according to perfusion CT study, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were assessed. Main mechanism of injury in 27 of 40 (67.5%) patients was acceleration-deceleration due to traffic accidents which usually leads to diffuse axonal injury (DAI) of different severity. In the other 13 (32.5%) cases injury was associated with coup-countercoup mechanism which caused focal contusions mostly. Not only GCS score but CT-signs of DAI severity, intracranial hemorrhage and minimal levels of CPP had significant prognostic value. Results of perfusion CT studies demonstrated that in 37 of 40 (92.5%) patients cerebral blood flow decreased (below 28.6 ml/100 g/min) in one or more arterial blood distribution areas. Increase of CBF was registered in 9 cases (over 69 ml/100 g/min), in 6 of them elevation of CBF in one arterial distribution area was associated with reduction in the other. Generally, mean CBF values were higher in the middle cerebral artery circulation than in the other. The lowest CBF levels (16.3 +/- 6 ml/100 g/min) were observed in cortical and subcortical hemorrhagic foci while these values were significantly higher in the same contralateral intact zones (36.0 +/- 10.0 ml/100 g/min; p < 0.01). In 3 patients with DAI the CBF in the midbrain varied from 12.5 to 30.1 ml/100 g/min with the lowest levels in hemorrhagic focus in cerebral peduncle. It corresponded to cystic-atrophic alterations found on subsequent follow-up MRI. Thus, reduction of CBF and episodes of low CPP were the leading pathophysiological phenomena of diffuse and focal brain damages.     

Concurrent changes in intracranial pressure,cerebral blood flow velocity,and brain energy metabolism in rabbits with acute intracranial hypertension

The relationship between intracranial pressure or cerebral perfusion pressure (CPP), cerebral blood flow, and brain energy failure is unpredictable throughout the development of acute intracranial hypertension. The purpose of the present study was to correlate intracranial pressure with cerebral blood flow velocities and brain energy metabolism in adult rabbits. The acute intracranial hypertension was achieved by pressure transmission. Transcranial Doppler waveforms were obtained from the basilar artery for monitoring cerebral blood flow velocities. ³¹P-Magnetic resonance spectroscopy was used to assess brain energy metabolism. The diastolic blood flow velocity began to decrease significantly (34.5%) when the intracranial pressure was equal to half the diastolic arterial pressure for a CPP of 36±18 mmHg. Circulatory cerebral resistances increased significantly (55%) for the same value of CPP. Diastolic frequency was near zero when intracranial pressure approached diastolic arterial pressure (51±12 mmHg), corresponding to a CPP of 30±15 mmHg. At the same time, only a tendency for brain energy metabolism to decrease was observed. Consequently, transcranial Doppler sonography could be proposed for the followup of intracranial hypertension. Magnetic resonance spectroscopy could help to monitor these patients and could be especially proposed in case of high intracranial pressure (near diastolic arterial pressure). The joint ue of these two methods would help in making appropriate therapeutic decision in humans.     

重型脑创伤患者脑细胞间液甘油浓度研究

目的研究重型脑创伤后影响脑细胞间液甘油(Gly)浓度变化的因素。方法连续监测53例重型颅脑创伤患者近损伤区脑细胞间液Gly浓度和局部脑血流(CBF),同时监测颅内压(ICP)及脑灌注压(CPP)。选择每小时CPP和CBF的最小值及ICP的最大值与该小时的Gly浓度匹配。根据局部CBF、ICP、CPP及预后将所有Gly样品分组。结果(1)Gly、CCP及CBF与预后的关系:与中残或重残组比较,植物生存或死亡组患者Gly显著增高而CCP及CBF显著降低(P<0.05);与恢复良好组比较,中残或重残组Gly显著增高而CCP及CBF显著降低(P<0.05)。(2)ICP,CCP,CBF对Gly的影响:ICP>15mmHg组、CCP<70mmHg组及CBF<50AU分别比ICP<15mmHg组、CCP>70mmHg及CBF50￣150AU组Gly浓度显著增高(P<0.01)。(3)病理类型和Gly浓度的关系:弥漫性轴索损伤Gly浓度最高,比硬膜外血肿及硬膜下血肿显著增高(P<0.05),但与脑挫裂伤患者无显著差异。结论Gly浓度可以反映原发和继发性脑损伤的严重程度,是细胞膜降解和脑缺血的可靠指标。     

Alterations in behavior, brain electrical activity, cerebral blood flow, and intracranial pressure produced by triethyl tin sulfate induced cerebral edema.

The interrelationships between cerebral edema, intracranial pressure (ICP), and cerebral blood flow (CBF) were studied in acute and chronic triethyl tin sulfate treated rats. Prior to pentobarbital anesthesia behavioral observations were made. ICP and regional CBF were measured under steady state conditions and brain water content was determined by vacuum drying of the right cerebral hemisphere. Control and chronic animals were neurologically normal. There were two distinct acute groups: (1) acute low pressure (ALP) animals - alert but tetraperetic, and (2) acute high pressure (AHP) animals - deeply stuporous, with minimal pain response and gross EEG slowing. ICP was significantly elevated only in AHP animals. Hemispheric CBF was significantly reduced in AHP and chronic animals. The interaction of increased pressure and edema (AHP) produced the greatest decrease in CBF, although deep white flows were significantly affected in all experimental groups. Chronic animals had significantly lower flow in four of seven regions compared to ALP animals despite no significant difference in ICP. Water content was significantly increased in all experimental groups with the greatest increase in the chronic animals. In the absence of any significant increase in ICP, cerebral edema appears to cause a significant reduction in cerebral blood flow and this reduction corresponds with the magnitude and location of the edema.     

Significance of a reduced cerebral blood flow during the first 12 hours after traumatic brain injury

Background: It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain’s injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF. Methods: We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed. Results: Average global CBF for the 77 patients was 36±16 mL/100g/minutes. Nine patients had an average global CBF <18 (average 12±5). The remaining 68 patients had a global CBF of 39±15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF≥18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury. Conclusion: In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.     

急性颅内高压时呼气末正压通气对脑氧代谢的影响

目的 观察呼气末正压通气（PEEP）对急性高颅压犬脑氧代谢的影响。方法 8只犬,全麻、机械通气,自体血凝块注入右额叶脑内制成颅内高压模型,静脉滴注脂多糖诱发急性肺损伤,PEEP从0cmH2O开始每次增加3cmH2O水柱,直到18cmH2O,每个水平持续20min,在左侧额顶部用光纤颅内压探头监测颅内压（ICP）的变化,记录平均动脉压（MAP）并计算脑灌注压（CPP）。股动脉、左颈内静脉球部逆行置管采血,行血气分析并计算脑氧摄取（CEO2）和脑动静脉氧含量差（Da-jO2）,分析其与MAP、ICP和CPP的相互关系。结果 随着PEEP的递增,MAP下降,ICP,CPP均有不同程度下降,Da-jO2、CEO2呈上升趋势。血流动力变化与脑氧代谢之间无明显相关性。结论 PEEP通气可改善氧合,但使脑灌注下降,血流动力指标与脑氧代谢指标之间无明显一致性,单用ICP、CPP不能完全判断组织灌注是否充分,有必要监测脑氧代谢,以指导设置PEEP水平。     

Role of the medullary vasomotor centre in the development of plateau waves

Plateau waves can sometimes be found in various neurosurgical patients with increased intracranial pressure (ICP). In spite of the clinical importance of the waves, the precise mechanism producing them is still obscure. It has been reported that the waves are often accompanied by a reduction of arterial blood pressure (ABP) and suppression of respiration, . suggesting a role of the brain stem in their development. In this study, we induced intracranial hypertension in dogs by occluding the neck veins, then stimulated the pressor and depressor areas of the brain stem, observing changes of ICP, ABP, cerebral blood flow (CBF), respiration and heart rate. Stimulation of the brain stem usually caused an increase in the ICP accompanied by variations of the ABP, CBF, respiration and heart rate. These variations were divided into two types: Type I and Type II. Type I which was induced by the stimulation of the pressor area of the brain stem comprised an arterial pressor response, an increase of CBF, hyperventilation and bradycardia. Type II which was caused by stimulation of the depressor area, included declines of the ABP and CBF, respiratory supression and bradycardia. Of these, variations observed in Type II were similar in many respects to the plateau waves observed in clinical practice. We suggest that the depressor area of the medullary vasomotor centre may play an important role in eliciting the cerebral vasomotor reaction in the development of plateau waves in intracranial hypertension.     

Role of the medullary vasomotor centre in the development of plateau waves

Plateau waves can sometimes be found in various neurosurgical patients with increased intracranial pressure (ICP). In spite of the clinical importance of the waves, the precise mechanism producing them is still obscure. It has been reported that the waves are often accompanied by a reduction of arterial blood pressure (ABP) and suppression of respiration, suggesting a role of the brain stem in their development. In this study, we induced intracranial hypertension in dogs by occluding the neck veins, then stimulated the pressor and depressor areas of the brain stem, observing changes of ICP, ABP, cerebral blood flow (CBF), respiration and heart rate. Stimulation of the brain stem usually caused an increase in the ICP accompanied by variations of the ABP, CBF, respiration and heart rate. These variations were divided into two types: Type I and Type II. Type I which was induced by the stimulation of the pressor area of the brain stem comprised an arterial pressor response, an increase of CBF, hyperventilation and bradycardia. Type II which was caused by stimulation of the depressor area, included declines of the ABP and CBF, respiratory suppression and bradycardia. Of these, variations observed in Type II were similar in many respects to the plateau waves observed in clinical practice. We suggest that the depressor area of the medullary vasomotor centre may play an important role in eliciting the cerebral vasomotor reaction in the development of plateau waves in intracranial hypertension.     

Effects of High-frequency Oscillatory Ventilation on Systemic and Cerebral Hemodynamics and Tissue Oxygenation: An Experimental Study in Pigs

Background

In this study, we compare the effects of high frequency oscillatory ventilation (HFOV) with those of lung-protective volume-controlled ventilation (VCV) on cerebral perfusion, tissue oxygenation, and cardiac function with and without acute intracranial hypertension (AICH).

Methods

Eight pigs with healthy lungs were studied during VCV with low tidal volume (V_T: 6 ml kg⁻¹) at four PEEP levels (5, 10, 15, 20 cmH₂O) followed by HFOV at corresponding transpulmonary pressures, first with normal ICP and then with AICH.

Systemic and pulmonary hemodynamics, cardiac function, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), cerebral tissue oxygenation, and blood gases were measured after 10 min at each level. Transpulmonary pressures (TPP) were calculated at each PEEP level. The measurements were repeated with HFOV using continuous distending pressures (CDP) set at TPP plus 5 cmH₂O for the corresponding PEEP level. Both measurement series were repeated after intracranial pressure (ICP) had been raised to 30–40 cmH₂O with an intracranial balloon catheter.

Results

Cardiac output, stroke volume, MAP, CPP, and CBF were significantly higher during HFOV at normal ICP. Systemic and cerebral hemodynamics was significantly altered by AICH, but there were no differences attributable to the ventilatory mode.

Conclusion

HFOV is associated with less hemodynamic compromise than VCV, even when using small tidal volumes and low mean airway pressures. It does not impair cerebral perfusion or tissue oxygenation in animals with AICH, and could, therefore, be a useful ventilatory strategy to prevent lung failure in patients with traumatic brain injury.

     

Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats

Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 μL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1±23.0 versus 21.1±11.8 mm³; P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.     

弥漫性脑损伤大鼠颅内压及脑灌注压的变化及DCLHb治疗作用

目的：研究大鼠加速性弥慢性脑损伤合并低血压及脑缺血、缺氧时，颅内压（ＩＣＰ）及脑灌注压（ＣＰＰ）变化与双阿斯匹林联偶血红蛋白液（ＤＣＬＨｂ）治疗作用。方法：２４只ＳＤ大鼠随机分为假手术对照、脑损伤并低血压与脑缺血及治疗三组。采用Ｍａｒｍａｒｏｕ大鼠加速性弥慢性脑损伤模型，抽血及颈动脉结扎造成低血压及脑缺血、缺氧。所有动物均气管内插管并实施同步生理监护。结果：伤后４小时，与假手术组对比，合并低血压与脑缺血组出现ＩＣＰ增高及ＣＰＰ降低（Ｐ＜０．０５），ＤＣＬＨｂ治疗组二者接近正常。结论：合并低血压与脑缺血组出现ＩＣＰ增高及ＣＰＰ降低提示低血压或脑缺血参予脑损害的加重过程，ＤＣＬＨｂ则可能通过提高ＣＰＰ发挥脑保护作用。     

Effects of S-nitrosoglutathione on acute vasoconstriction and glutamate release after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) causes acute vasoconstriction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide (NO) may contribute to acute vasoconstriction. Therefore we examined the effect of the NO donor N-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH. METHODS: SAH was induced by the endovascular suture method in anesthetized rats. GSNO (1 micromol/L/kg, n=31) or saline (n=21) was injected 5 minutes after SAH. Sham-operated rats received GSNO (1 micromol/L/kg, n=5) 5 minutes after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH. SAH size was determined, and vascular measurements were made histologically. RESULTS: GSNO had no effect on resting blood pressure, intracranial pressure, cerebral perfusion pressure, or CBF in sham-operated animals. However, administration of GSNO after SAH was associated with significantly increased CBF (161.6+/-26.6% versus saline 37.1+/-5.5%, 60 minutes after SAH, P<0.05), increased blood vessel diameter (internal carotid artery [ICA] 285.0+/-16.5 microm versus saline 149.2+/-14.1 microm, P<0.01), decreased vessel wall thickness (ICA12.9+/-0.7 microm versus saline 25.1+/-1.6 microm, P<0.01), and decreased extracellular glutamate levels (3315.6+/-1048.3% versus saline469. 7+/-134.3%, P<0.05). Blood pressure decreased transiently, whereas intracranial pressure, cerebral perfusion pressure, and SAH size were not affected. CONCLUSIONS: These results suggest that GSNO can reverse acute vasoconstriction and prevent ischemic brain injury after SAH. This further implies that acute vasoconstriction contributes significantly to ischemic brain injury after SAH and is mediated in part by decreased availability of NO.