Endoscopic technique: a new model of subarachnoid hemorrhage in rats

It has become increasingly evident that the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage (SAH) which described the ischemic consequences of cerebral arterial constriction is complex and multifactorial. In an attempt to study cerebral vasospasm, numerous investigators have used experimental animal models that resemble cerebral vasospasm in humans. No ideal model for SAH has been found as yet, and hence the quest for such a model continues. We developed an endoscopic technique that permits a direct vision of internal carotid artery and puncturing the artery to provoke SAH. This model will closely reflect the clinical setting of an aneurysm rupture. The onset of SAH was characterized by a sudden decrease of cerebral blood flow (CBF) and cerebral blood volume (CBV) by at least 40% in the first 20 min. Following this initial drop, there was an increase in the CBF and the CBV, however, they remained significantly below the base line values, at the end of 1 h. This study describes a new model of SAH in rat that simulates the clinical phenomenon of ruptured intracranial aneurysm that also produces cerebral vasospasm.     

Electrical Stimulation for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review

ObjectivesCerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm.Materials and MethodsWe performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords “electric stimulation,” “cerebral vasospasm,” “subarachnoid hemorrhage,” “sympathetic,” and “parasympathetic.” Additional papers were identified from the reference lists of the articles identified in the literature search.ResultsIncreased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included “reversible functional sympathectomy,” activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm.ConclusionElectrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.     

Type V phosphodiesterase expression in cerebral arteries with vasospasm after subarachnoid hemorrhage in a canine model

Abstract

Cyclic GMP (cGMP) mediates smooth muscle relaxation in the central nervous system. In subarachnoid hemorrhage (SAH), decreases in intrinsic nitric oxide (NO) cause cerebral vasospasms due to the regulation of cGMP formation by NO-mediated pathways. As phosphodiesterase type V (PDE V) selectively hydrolyzes cGMP, we hypothesized that PDE V may function in the initiation of vasospasm. This study sought to identify the altered PDE V expression and activity in the vasospastic artery in a canine SAH model. We also used this system to examine possible therapeutic strategies to prevent vasospasm. Using a canine model of SAH, we induced cerebral vasospasm in the basilar artery (BA). Following angiographic confirmation of vasospasm on day 7, PDE V expression was immunohistochemically identified in smooth muscle cells of the vasospastic BA but not in cells of a control artery. The isolation of PDE enzymes using a sepharose column confirmed increased PDE V activity in the vasospastic artery only through both inhibition studies, using the highly selective PDE V inhibitor, sildenafil citrate, and Western blotting. Preliminary in vivo experiment using an oral PDE V inhibitor at 0.83 mg kg^-1 demonstrated partial relaxation of the spastic BA. PDE V activity was increased from control levels within the BA seven days after SAH. PDE V expression was most prominent in smooth muscle cells following SAH. These results suggest that clinical administration of a PDE V inhibitor may be a useful therapeutic tool in the prevention of vasospasm following SAH. [Neurol Res 2002; 24: 607-612]     

Improved rat model for cerebral vasospasm studies

Abstract

While the rat has been used extensively in subarachnoid hemorrhage (SAH)-cerebral vasospasm studies, concerns exist whether this animal represents a usable model because its time course and pattern of cerebral vasospasm following SAH is not comparable to that observed in man. At present, our knowledge of the rat model is based almost exclusively on studies using a 'single hemorrhage' method. Since there is a positive correlation between severity of cerebral vasospasm, and volume of subarachnoid blood, an obvious question is whether the rat will show modifications in vascular responses when insulted by a second SAH. Here, an SAH was produced in rats using a 'double hemorrhage' method. Following SAH, cerebral arteries showed pathological alterations, significant decreases in luminal perimeter, and increases in arterial wall thickness, over a 7-day post-SAH period. The above vascular features are considered to be indicative of cerebral vasospasm and their presence over a 7-day post-SAH period represents a significant time extension when compared to a single hemorrhage. These modified vascular responses made the double hemorrhaged rat a much-improved animal model. [Neurol Res 2001; 23: 761-766]     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage

Abstract

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm. [Neurol Res 2001; 23: 715-720]     

Post-operative changes of cerebral circulation and metabolism in the acute stage of low-grade aneurysmal subarachnoid hemorrhage

Abstract

Objective: Pre- and post-operative cerebral circulation and metabolism were evaluated in patients with low-grade acute aneurysmal subarachnoid hemorrhage (SAH) who underwent early surgery to investigate the effects on brain dysfunction.

Methods: Positron emission tomography (PET) was performed to measure the regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF) and cerebral blood volume in four patients (one male and three females, mean age: 60.3 years) with low-grade SAH within 30 hours of onset. Post-operative PET was performed on the seventh post-operative day. No patient suffered clinical deterioration during the study. Pre-operative PET scans demonstrated significant global reduction of CBF and CMRO₂, compared to 16 normal control subjects, and no significant change in OEF. CBF and CMRO₂ reduction post-operatively improved to the normal control values. Post-operative OEF was significantly increased compared to the normal control value.

Conclusions: Patients with low-grade SAH have impairment of cerebral circulation and metabolism in the acute period, which improves after surgery. Early surgery for low-grade SAH, necessary to avoid rerupture of the aneurysm, did not worsen the impairment of cerebral circulation and metabolism. However, measures to protect the brain from perioperative damage are necessary to achieve the optimum outcome.     

Comparison of transcranial Doppler ultrasonography and positron emission tomography using a three-dimensional template of the middle cerebral artery

Abstract

Objective: Transcranial Doppler (TCD) measures blood flow velocities (BFV) and is an indirect method of assessing cerebral blood flow (CBF). Positron emission tomography (PET) is a direct method to measure CBF. This study evaluates the correlations between TCD and PET findings

Methods: Nine patients with a symptomatic carotid artery stenosis, who underwent CEA, were studied pre- and post-operatively on the ipsi- and contralateral sides. Measurements of the BFV, CO₂ reactivity, CBF, cerebral blood volume (CBV) and mean vascular transit time (MVTT) were performed using a three-dimensional volume of interest (VOI) for the middle cerebral artery (MCA).

Results: CBF in the MCA region, as measured with PET, shows a good correlation with BFV, as measured with TCD, with similar pattern for total, gray and white matter MCA territory (Pearson's correlation coefficients: 0.751, 0.748 and 0.748, respectively). This correlation was found in the pre-operative as well as the post-operative state. No association could be demonstrated between CO₂ reactivity and CBV or (Pearson's correlation coefficients: 0.051 and 0.166, respectively).

Conclusion: With PET, it is possible to create three-dimensional VOI of arterial territories. CBF measured in these VOI seems to correlate with BFV before and after CEA on ipsi- and contralateral sides, while CBV shows no association with pre-operative CO₂ reactivity.     

Visit-to-Visit Blood PressureVariations and Hemodynamic Deterioration in Atherosclerotic Major Cerebral ArteryDisease

ObjectiveVisit-to-visit variations in blood pressure (BP) in patients with atherosclerotic major cerebral artery disease could impair the function of cerebral collaterals, leading to hemodynamic deterioration at follow-up. However, few studies have investigated the relationship between visit-to-visit BP variability and changes in hemodynamic parameters at follow-up.Materials and methodsWe evaluated 35 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischemic episodes during follow-up (mean: 35 ± 20 months); these patients had a three-time visit for positron emission tomography examinations with ¹⁵O-gas. Differences in the mean hemispheric values of hemodynamic parameters in the cortical territory of the diseased artery between the first and third examinations (changes at follow-up) were correlated with the coefficient of variation (CoV) in three systolic BP (SBP) values at the three examinations (BP variability during follow-up).ResultsCoV values were negatively correlated with changes in oxygen metabolism or cerebral blood flow/cerebral blood volume (CBF/CBV) ratio. In 17 patients with higher CoV values (> group median, 0.072), decreases in CBF, cerebral metabolic rate of oxygen, and CBF/CBV ratio were observed at follow-up; CBV decreased in 18 patients without elevated CoV. A higher CoV was associated with a lack of statin use.ConclusionIn patients with atherosclerotic major cerebral artery disease, high visit-to-visit SBP variations during follow-up may be associated with deterioration in cerebral hemodynamics and metabolism.     

Whole brain CT perfusion combined with CT angiography in patients with subarachnoid hemorrhage and cerebral vasospasm

Objective

To assess cerebral vasospasm (CVS) and monitor cerebral microcirculatory changes in patients with acute subarachnoid hemorrhage (SAH) via CT angiography (CTA) combined with whole-brain CT perfusion (CTP) techniques.

Methods

Sixty patients with SAH (SAH group) and 10 patients without SAH (control group) were selected for a prospective study. CTP combined with CTA and digital subtraction angiography (DSA) studies were performed on patients with initial onset of SAH less than three days. CTA and DSA as well as the CTP parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) were acquired and analyzed. The relationship of CTA and CTP measurements was assessed in these acute SAH patients.

Results

CTP techniques were used to achieve the perfusion maps of the whole brain in patients with acute SAH. Compared to the control group, mean CBF value was significantly lower while both MTT and TTP values were significantly higher in SAH group (all p < 0.05). Further analysis revealed that mean CBF in patients with CVS, sCVS, Fisher III–IV and Hunt–Hess III–V significantly decreased when compared to patients with nCVS, asCVS, Fisher I–II and Hunt–Hess I–II (p < 0.05). Furthermore both MTT and TTP values were also significantly reduced in patient with CVS, sCVS, Fisher III–IV and Hunt–Hess III–V (p < 0.05).

Conclusion

The study demonstrated that changes of microcirculation in patients with SAH could be assessed by whole-brain CTP. CTP combined with CTA could detect both macroscopic evident vasospasm on CTA and alterations of microcirculation on CTP. Mean CBF was significantly lower in patients with SAH.     

Spontaneous disappearance and reappearance of a ruptured cerebral aneurysm: One case found in a group of 33 consecutive patients with subarachnoid hemorrhage who underwent repeat angiography

Abstract

The spontaneous disappearance and reappearance of a ruptured cerebral aneurysm is generally assumed to be a rare phenomenon although the actual Incidence Is unknown. Among 39 consecutive cases of acute subarachnoid hemorrhage (SAH), 33 were studied by three-dimensional computed tomographic angiography (CTA) within 6 h after the onset of SAH, followed by digital subtraction angiography (DSA) within 24 h after the ictus. Of those patients, one, a 58-year-old woman, had a saccular aneurysm at the distal anterior cerebral artery; the aneurysm was clearly demonstrated by CTA 2.5 h after the SAH onset, but was not shown by a subsequent DSA performed 8.5 h after the ictus. A follow-up DSA detected the neck of aneurysm on day 11, and the whole aneurysm was visualized on day 19. The observations in this particular case suggest that the spontaneous disappearance of a ruptured cerebral aneurysm may occur during the ultra-early stage of SAH and that reappearance may follow during the next few weeks. The patient did not suffer complications such as vasospasm or systemic hypotension nor was she treated with antifibrinolytic agents. The aneurysmal shape and the surrounding clot are considered as putative factors possibly related to the intermittent appearance of the aneurysm. [Neurol Res 2000; 22: 583-587]     

Slow oscillations in middle cerebral artery cerebral blood flow velocity and aging

Abstract

Objective: A recent study using near infrared spectroscopy (NIRS) showed that low frequency oscillations of regional cerebral blood flow (CBF) decline with age. Using transcranial Doppler ultrasound (TCD), it is possible to monitor similar fluctuations in cerebral blood velocity (CBV) in basal cerebral vessels. Such oscillations have been used widely in the assessment of cerebral autoregulation. We postulated that it should be possible to observe similar age related reductions in the amplitude of slow waves recorded using TCD.

Methods: We studied 187 patients with head injury, who were admitted to Addenbrooke's Neuro Critical Care unit between 1992 and 1998. Intermittent recordings of CBV were undertaken using TCD, which were subsequently analysed using software developed in-house. Power spectra were computed in the very low frequency (VLF: 0.01–0.05 Hz) and low frequency (LF: 0.07–0.11 Hz) ranges for all signals and a regression analysis was performed to assess the correlation between power in each frequency band and age.

Results: No significant correlation was found between VLF or LF power and age (VLF: r=0.037; p=0.63; LF: r=?0.05, p=0.517).

Discussion: While remaining cogniscent of the complex nature of our patient group, we find that age dependent reductions in CBF oscillations seen using NIRS do not translate to recordings of CBV in the middle cerebral artery in patients with head injury.     

Spasm index in subarachnoid haemorrhage: consequences of vasospasm upon cerebral blood flow and oxygen extraction

A spasm index, defined as transcranial Doppler detected flow velocity in the middle cerebral artery divided by regional cortical cerebral blood flow (CBF), was used on 24 patients with subarachnoid haemorrhage (SAH). The aim was to estimate degree and time course of vasospasm, even in cases with great day-to-day variation in CBF, and correlate to CBF and oxygen extraction. All patients showed increase in spasm indices with peak index in the second or third week. The index seemed stable in spite of day-to-day fluctuations in CBF. Severe vasospasm were associated with poor clinical condition, reduced CBF (less than 30) and high AVDO2. The same picture could be seen with minor degree of vasospasm, probably, in some cases, due to high intracranial pressure. The results suggest that the spasm index is useful in monitoring patients with subarachnoid haemorrhage, and that severe vasospasm has a negative influence on clinical condition, CBF and oxygen extraction.     

Transdermal nitroglycerin in patients with subarachnoid hemorrhage

Delayed ischemic neurological deficit (DIND) following cerebral vasospasm remains a cause for high morbidity and mortality in patients with subarachnoid hemorrhage (SAH). There is experimental and clinical evidence of positive effects of nitric oxide (NO) donors on cerebral vasospasm. We therefore analysed the effect of transdermal nitroglycerin in patients with SAH measuring transcranial Doppler velocities (TCD), cerebral blood flow (CBF) and DIND. Nitroglycerin was used in a target dose of 14 microg/kg/h. TCD assessment was performed daily. CBF measurements were done using the perfusion CT-technique. Blood pressure, volume intake and vasopressor administration, were registered. Nine patients were randomly assigned either to the nitroglycerin group (N-group) and eight patients in the control group (C-group). Mean TCD values in the extracranial portion of the internal carotid artery (ICA) were lower in the N-group (p<0.005). Mean TCD in the middle cerebral arteries (MCA) showed no difference. The Lindegaard ratio was higher in the N-group (p<0.04). CBF in the N-group was higher than in the C-group (p<0.03). Even though nitroglycerin reduces blood pressure and lowers ICA TCD-values and increases the Lindegaard ratio, a higher CBF was measured in the N-group. Thus, nitroglycerin influences the cerebral vascular tone and increases CBF. SAH therapy with nitroglycerin is possible without increasing the risk of DIND. The exact timing of onset, duration and reduction of nitroglycerin administration in respect to the appearance of vasospasm may have a strong impact on the success of such a therapy.     

Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared. METHODS: On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient). RESULTS: HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups. CONCLUSIONS: HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit.     

蛛网膜下腔出血并迟发性脑血管痉挛大鼠脑能量代谢与脑血流量变化的实验研究

目的探讨实验性蛛网膜下腔出血导致的迟发性脑血管痉挛时脑能量代谢的变化规律，及其与皮质脑血流量（CBF）变化的相关性。方法50只雄性SD大鼠随机分为对照组和蛛网膜下腔出血第1、3、5、7天组．应用非抗凝自体动脉血枕大池两次注血法制备蛛网膜下腔出血大鼠模型；另5只大鼠用于颅内血液大体分布的观察。应用微透析仪监测各组大鼠脑组织间液中葡萄糖（Glu）、乳酸（Lac）及丙酮酸（Pyr）含量，并计算乳酸／丙酮酸比值；激光多普勒血流仪监测各组大鼠皮质脑血流量；于光学显微镜及透射电子显微镜下观察基底动脉血管壁的病理学改变。结果（1）5只用于观察颅内血液大体分布的大鼠中4只蛛网膜下腔出血模型鼠血液主要分布于基底池、脚间池及额叶底面，亚甲蓝与血液混合物主要沉积于颅底．同时在脑室及纵裂池亦可见血液分布；余1只注入人工脑脊液后未发生颅内出血及血液沉积。表明蛛网膜下腔出血动物模型制备成功。（2）与对照组相比，蛛网膜下腔出血组大鼠葡萄糖及丙酮酸含量明显降低（P〈0．01）；乳酸／丙酮酸比值明显升高（P〈0．01），以第5、7天组升高最为明显（P〈0．01）；第5天组乳酸含量亦明显升高（P〈0．01）。（3）激光多普勒监测显示，蛛网膜下腔出血组大鼠脑血流量减少率高于对照组（P〈0．05），其中第5天组减少最为显著。与其他各亚组比较差异有统计学意义（尸〈0．05）；脑血流量变化与乳酸／丙酮酸比值、乳酸水平的改变呈正相关（r=0．721，0．477；均P〈0．01），与葡萄糖、丙酮酸水平的改变呈负相关（r=-0．447，-0．579；均P〈0．01）。结论微透析指标与脑血流量变化具有一致性，可作为蛛网膜下腔出血脑组织间液生化指标的动态监测，用于预测迟发性脑血管痉挛的发生。     

High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients

ObjectiveThe goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients.MethodsThis study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis.ResultsNinety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups.ConclusionThis study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.     

Changes in Cerebral Perfusion with Induced Hypertension in Aneurysmal Subarachnoid Hemorrhage: A Pilot and Feasibility Study

Background

The effects of induced hypertension (IH) on cerebral perfusion after subarachnoid hemorrhage (SAH) are unclear. The objectives of this investigation are to: (1) determine whether there are differences in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) measured with computed tomography perfusion (CTP) before and after IH; (2) evaluate differences in the presence of infarction and clinical outcome between patients with and without IH.

Methods

We performed a retrospective cohort analysis of 25 aneurysmal SAH patients. IH was initiated as per the standard institutional protocol when patients showed clinical symptoms of delayed cerebral ischemia (DCI). Differences in CBF, CBV, and MTT between early (<72 h after aneurysm rupture) and late (7–10 days after aneurysm rupture) CTP were quantified in patients with (n = 13) and without IH (n = 12). Outcome measures included cerebral infarction and clinical outcome at 3 months.

Results

Early MTT was significantly greater in the IH group compared to the no-IH group. There was no difference in early or late CBV or CBF between the two groups. In patients that received IH, there was a significant decrease in MTT between the early (7.0 ± 1.2 s) and late scans (5.8 ± 1.6 s; p = 0.005). There was no difference in the incidence of infarction (5/13 vs. 2/11) or poor outcome (3/11 vs. 6/13) between the IH and no-IH groups, respectively (p > 0.05).

Conclusions

Elevated MTT is a significant factor for the development of DCI in patients eventually requiring IH therapy and is improved by IH treatment. Therapies to prevent DCI and improve clinical outcome may need to be initiated earlier, when cerebral perfusion abnormalities are first identified.

     

Doppler ultrasound measurement of blood flow volume in the extracranial internal carotid artery for evaluation of brain perfusion after aneurysmal subarachnoid hemorrhage

Monitoring of cerebral blood flow (CBF) is an essential part in the early diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Several methods have been established to monitor cerebral perfusion in these patients. During last few years, a new sonographic approach has been introduced, the so called 'angle independent ultrasound system' for monitoring volume flow in the internal carotid artery (ICA). The angle independent Doppler ultrasound system Quantix ND (Cardiosonix Ltd, Israel) determines the diameter of the ICA as well as the velocity of blood flow in the extracranial part of this vessel. Thus, a determination of the global CBF in the anterior circulation can be achieved. Aim of our study was to compare the Quantix ND system and the commonly used transcranial Doppler sonography (TCD) in patients suffering from aneurysmal SAH. We included 11 patients (eight female and three male; Hunt and Hess I-V) and performed post-operatively/post-interventionally daily measurement of blood flow volume in the ICA, and determined the blood flow velocity in middle and anterior cerebral artery (MCA and ACA) with TCD. Six patients post-operatively/post-interventionally developed cerebral vasospasm, resulting in ischemia and territorial infarction. Three patients were chosen as case studies. In contrast to the TCD, we found a strong significant correlation of blood flow volume with Quantix ND in the ICA and the occurrence of cerebral infarction (p<0.001). These preliminary data justify further investigation of this angle independent Doppler ultrasound device. We postulate that this new tool might be effective for monitoring the CBF in the critical post-operative/post-interventional interval following aneurysmal SAH.     

A new model of subarachnoid hemorrhage in experimental animals with the purpose to examine cerebral vasospasm

Using 20 rabbits, we tried to establish a new model of experimental subarachnoid hemorrhage (SAH) for examining both acute and chronic cerebral vasospasm. A cranial opening was drilled, and a puncture made on the posterior branch of the middle cerebral artery. A second puncture was made in the superior sagittal sinus for additional withdrawal of subarachnoid blood. The bleeding thus induced resulted in arterial spasm which was studied by using serial electrocorticograms, cerebral blood flow measurement with 133Xe, and videomicroscopy of the small pial vessels at various intervals. After death of the animals, the brains were observed to identify the extention of the bleeding. It was indeed obvious that large amounts of subarachnoid blood clots had accumulated. This investigation showed that the rabbit can be used as a new experimental model of SAH. With a two-puncture method, it is possible to simulate the clinical phenomenon of a ruptured aneurysm, that seems to produce acute and chronic cerebral vasospasm. For the latter, the accumulation of blood clots in the basal surfaces plays an important role. The three methods of observation, videomicroscopy, cerebral blood flow measurements, and electrocorticography appeared to provide useful information in the study of biphasic vasospasm in the rabbit.     

High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms

Abstract

We studied the incidence and timing of hyponatremia (Na < 135 mEq l~¹) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na < 130 mEq^-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p < 0.01) and severe hyponatremia (p< 0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p < 0.05), in cases with vasospasm (p < 0.001), and in cases with hydrocephalus (p < 0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 ±4.4 and day 10.6± 5.8 following SAH, representing a 3-day delay for hyponatremia (p<0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm. [Neurol Res 2000; 22: 151-155