Degree Of Vasospasm Research Articles

Acute Neonatal Upper Limb Ischemia: Topical Vasodilation, Anticoagulation and Physical Therapy-A new option for complete reversal of ischemia

Acute upper limb ischemia in neonates is extremely rare and oftenassociated with disastrous outcomes including digital gangrene, chroniclimb ischemia, sepsis and limb loss. It is usually seen in the contextof intra-arterial catheters in the preterm neonates but it can be alsoseen in cases of difficult or traumatic deliveries as well as in infantswith coagulation deficits but can also be spontaneous with no obviousaetiology. Treatment options include topical vasodilators, systemicanticoagulation and in some instances, surgical intervention. We reportthree cases of acute limb ischemia in preterm neonates in which anew treatment option was introduced. The neonates responded to acombination of topical nitro-glycerine cream, systemic anticoagulationwith heparin and physical light massaging of the area just proximalto the site of reduced flow in the vessel assuming some degree ofvasospasm of the vessel occurs with or without thrombosis.Keywords: neonatal ischemia, management of neonatal ischemia, topicalvasodilators, systemic anticoagulation, massage therapy, surgicalintervention

Role of serum biomarkers and transcranial Doppler in predicting cerebral vasospasm after aneurysmal subarachnoid hemorrhage

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) can have serious consequences related to vasospasm and delayed cerebral ischemia (DCI). Serum biomarkers have emerged as a promising assessment tool to facilitate earlier diagnosis of cerebral vasospasm (CV) and to identify pre-clinical vessel narrowing.ObjectivesOur aim was to detect the predictive value of serum biomarkers such as von Willebrand factor (vWF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase9 (MMP-9) in CV after aSAH.Subjects and methodsThirty five patients with recent aSAH were included. Patients were divided into two groups; 19 patients (CV group) and 16 patients (non-CV group). The CV group was further subdivided into 9 symptomatic (DCI) and 10 asymptomatic patients. All patients underwent transcranial Doppler (TCD) evaluations three times a week for 2 weeks measuring the mean flow velocities. Serum level of vWF, MMP-9, and VEGF were assessed twice (at onset and within 2 weeks).ResultsA statistically significant increase in serum biomarker levels was found in the CV group. Cutoff value for vWF, MMP-9, and VEGF were > 4985 ng/ml, > 495 ng/ml, and > 184 pg/ml, respectively. Statistically significant positive correlations were found between serum levels of biomarkers and degree of vasospasm. No difference was found in the biomarkers between symptomatic CV and asymptomatic CV.ConclusionSerum biomarkers are a reliable tool to predict CV following aSAH, their levels reflect the severity of vascular vasospasm, yet, they cannot predict DCI. TCD has a strong role in early detection, monitoring of post subarachnoid vasospasm and successfully capturing asymptomatic DCI.

Vasospasm as a major complication after acute mechanical thrombectomy with stent retrievers

ObjectiveMechanical thrombectomy using a stent retriever for acute large vessel occlusion is indispensable in stroke treatment, however, vasospasm may occur. The objective of this retrospective study was to investigate which cases are more likely to experience vasospasm after thrombectomy with stent retrievers. MethodsWe included 29 patients diagnosed with acute cardiogenic cerebral embolism who were treated with stent retrievers at our facility from December 2014 to December 2017. Atherothrombotic brain infarction cases were excluded because it was difficult to evaluate for vasospasms. Vasospasm was defined as reversible arterial narrowing of <80% of the normal vessel diameter after usage of the stent retriever. The age, sex, type of stent retriever, occlusion site, number of procedures, thrombolysis in cerebral infarction (TICI) grade, degree of vasospasm, intracranial hemorrhage by the procedure, and neurological outcomes were analyzed. ResultsAmong the 29 cases, 12 (41.4%) resulted in vasospasm; nine cases were mild (20–50% stenosis) and 3 cases were severe (≥50% stenosis). Vasospasm frequently occurred in the distal part of the anterior circulation when compared to the proximal part. In addition, the frequency of vasospasm increased as the number of procedures increased. Pooled analysis showed significant difference in the intravenous tissue-type plasminogen activator group (P = 0.029). There was no significant difference in the other groups. ConclusionStent retrievers appear to cause vasospasm more than expected when including mild cases. Vasospasm tends to occur especially in cases with IV-tPA; prognosis is generally good, and it rarely requires any treatment.

Effects of music nursing on PICC catheterization in premature infant

Objective To explore the effects of music nursing on relieving vasospasm and pain in premature infant during peripherally inserted central catheter (PICC) , so as to provide reference for the popularization and utilization of music nursing. Methods A total of 35 premature infants with vasospasm during the course of PICC catheterization from June 2015 to January 2017 were selected as the experimental group, and given music nursing. Another 35 premature infants with vasospasm during the course of PICC catheterization between January 2014 and June 2015 were selected as the control group, and given routine nursing care. The pain degree was compared by Premature Infant Pain Profile (PIPP) , and the relieving degree of vasospasm was monitored at the same time. Results After the intervention, the score of PIPP of the two groups both decreased. The PIPP score of the experimental group was (7.12±2.03) , while that of the control group was (8.14±2.12) , and the difference was statistically significant (t=2.600, P<0.05) . In the experimental group, there were 11 cases of complete remission and 24 cases of mild remission. In the control group, there were 8 cases of complete remission, 20 cases of mild remission and 7 cases of no remission. The difference between the two groups was statistically significant (χ2=7.837, P<0.05) . After the intervention, the sleep time of the children increased in both groups (P<0.05) . The sleep time of the experimental group was higher than that of the control group, and the difference was statistically significant (P<0.05) . Conclusions Music nursing can effectively relieve vasospasm and pain in children during PICC catheterization which is worthy of popularization and application. Key words: Infant, premature; Pain; Vasospasm; Peripherally inserted central catheter; Music nursing

Safety and efficacy of balloon angioplasty of the anterior cerebral artery for vasospasm treatment after subarachnoid hemorrhage.

Balloon angioplasty is often performed for symptomatic vasospasm following aneurysmal subarachnoid hemorrhage. Angioplasty of the anterior cerebral artery (ACA), however, is perceived to be a challenging endeavor and not routinely performed due to technical and safety concerns. Here, we evaluate the safety and efficacy of balloon angioplasty of the anterior cerebral artery for vasospasm treatment. Patients with vasospasm following subarachnoid hemorrhage who underwent balloon angioplasty at our institution between 2011 and 2016 were retrospectively reviewed. All ACA angioplasty segments were analyzed for pre- and post-angioplasty radiographic measurements. The degree of vasospasm was categorized as mild (<25%), moderate (25-50%), or severe (>50%), and relative change in caliber was measured following treatment. Clinical outcomes following treatment were also assessed. Among 17 patients, 82 total vessel segments and 35 ACA segments were treated with balloon angioplasty. Following angioplasty, 94% of segments had increased caliber. Neurological improvement was noted in 75% of awake patients. There were no intra-procedural complications, but two patients developed ACA territory infarction, despite angioplasty treatment. We demonstrate that balloon angioplasty of the ACA for vasospasm treatment is safe and effective. Thus, ACA angioplasty should be considered to treat vasospasm in symptomatic patients recalcitrant to vasodilation infusion therapy.

Abstract 193: Real-time Quantitative Changes in Cerebral Blood Flow From Intra-arterial Vasodilator Treatment in Cerebral Vasospasm

Introduction: Intra-arterial (IA) vasodilators are key components in the treatment of cerebral vasospasm (CV) resulting from subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI). Angiographic assessments of vessel caliber immediately after infusion, however, are unreliable metrics of treatment effect, and as a result there does not currently exist a clear biomarker against which to titrate treatment. Quantitative cerebral blood flow (CBF) measurements from angiographic images may better characterize treatment effect and provide real-time feedback to guide infusion protocols. Methods: From our prospectively maintained institutional registry, we identified patients treated with IA vasodilators in the anterior circulation for CV between July 2014 and June 2016. Angiograms were reviewed by an experienced neuro angiographer blinded to clinical data and subsequent imaging. Regions of interest (ROIs) were drawn by two experienced neuroimagers over the MCA territory. CBF maps were calculated automatically from immediate pre- and immediate post-infusion angiograms using perfusion angiography and averaged over the ROIs. Results: A total of 65 angiograms were evaluated from 22 patients treated with vasodilators for CV. Average age was 48 and 60% were female. Etiology of vasospasm included SAH in 83% (54/65), TBI in 14% (9/65) and stroke/vasculopathy in 3% (2/65) Degree of vasospasm varied from mild (20% (13/65)) to moderate ((62% (40/65)) and severe (18% (12/65)). All patients were treated with IA verapamil ranging from 5 mg to 30 mg over the course of 10-60 minutes. Immediate post-infusion angiograms demonstrated improved vascular caliber in 23% (15/65) cases. In comparison, CBF increased on average 11% (SD 49) after verapamil infusion. Verapamil dosage correlated with percent change in CBF (p&lt;0.05, Spearman’s correlation). Conclusions: Verapamil infusion resulted in increased CBF in patients with CV from SAH and TBI. Quantitative angiographic CBF may serve as an effective real-time biomarker of treatment efficacy.

A novel swine model of subarachnoid hemorrhage-induced cerebral vasospasm.

One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine. Twelve female swines (57 ± 3 kg) were injected twice (with a 2-day interval between injections) with autologous blood into the subarachnoid space at the level of C2-3 vertebrae. Different volumes were injected to identify clinical and radiological changes. The effect of volume variations on hematoma size and vasospasm intensity in the circle of Willis arteries were studied 7-14 days after the first injection using ascending pharyngeal angiographic measurements of vessel diameter. Neurological outcome using a modified scoring table based on clinical parameters (e.g., appetite, behavior, walking, posture, and eye movement) was recorded. Our results demonstrate that between volume combinations, intrathecal injection of 12 ml followed by 15 ml, with a 2-day interval in between, resulted in the most extensive angiographically-assessed vasospasm 12 ± 2 days following the first injection. The degree of vasospasm in the intracranial internal carotid artery was 22% and 16% for the left and right sides, respectively. Vasoconstriction of the anterior cerebral artery was 34% and 27% for the left and right sides, respectively. The vasoconstriction was not associated with either overt clinical signs or clinical outcome, which is indicative of an ischemic event. The relative scarcity of swine models for SAH-induced vasospasm motivated us to develop and quantify a straightforward protocol for producing consistent mild-to-moderate vasospasm following SAH. As swine is commonly used in translational cardiovascular research, we believe that this study constitutes an important phase in the study of SAH and in developing pharmacological agents and medical devices for interventions.

Digital ischaemia during cooling is independently related to nailfold capillaroscopic pattern in patients with Raynaud's phenomenon.

The aim of the study was to assess the association between plethysmographically measured vasospasms during stepwise cooling and recovery, as an index for digital ischaemia, and nailfold capillaroscopic pattern (NCP) severity in patients with primary or secondary RP, including SSc. In 381 consecutive patients with suspected RP without a history of digital ulcers, NCP (assessed by widefield videocapillaroscopy), fingertip photoelectric plethysmography during cooling and recovery and clinical characteristics were analysed. NCPs were graded as follows: normal, non-specific, early and active. The mean ischaemic time was defined as the mean time of perfusion loss during cooling and recovery of five fingers. In the patients with loss of perfusion during cooling and recovery, the NCP was normal in 152, non-specific in 96, early in 61 and active in 39 patients. The mean ischaemic time was positively associated with the severity of NCP, with P < 0.05 for each two- or three-grade increase and independent of underlying SSc. The difference was most pronounced during recovery. We demonstrate that the degree of vasospasm and ischaemia provoked by stepwise cooling and recovery are positively associated with NCP in patients with RP of different aetiologies and without a history of digital ulcers.

Canine double hemorrhage model of experimental subarachnoid hemorrhage.

Several animal subarachnoid hemorrhage (SAH) models have been proposed for the investigation of cerebral vasospasm. We describe the experimental procedures of a canine double-SAH model and also examine the model based on the canine physiological parameters and occurrence of angiographic delayed cerebral vasospasm using magnetic resonance (MR) imaging and digital subtraction angiography. Autologous blood was injected twice on days 1 and 3 in 36 beagles. All animals showed delayed angiographic vasospasm in the vertebrobasilar arteries on day 7. The degree of vasospasm was 29-42 % of the arterial caliber. MR imaging did not show any ischemic change. This animal model can produce definite delayed vasospasm without detectable cerebral infarction on MR imaging. The canine SAH model is suitable for the quantitative and chronological study of delayed angiographic vasospasm, but not for investigating early brain injury and delayed cerebral ischemia.

Double cisterna magna blood injection model of experimental subarachnoid hemorrhage in dogs.

Several animal subarachnoid hemorrhage (SAH) models have been proposed to study the etiology and treatment for cerebral vasospasm. We describe the experimental procedures of a canine double-hemorrhage model of SAH and discuss the pathophysiological parameters and occurrence of angiographic delayed cerebral vasospasm using magnetic resonance (MR) imaging and digital subtraction angiography. Autologous blood was injected twice on days 1 and 3 into the cerebellomedullary cistern of 36 female beagles. All animals showed delayed angiographic vasospasm in the vertebrobasilar arteries on day 7. The degree of vasospasm was 29-42% of the arterial diameter. However, this model showed no symptomatic vasospasm or ischemic changes detected by MR imaging. This animal model can produce reproducible delayed vasospasm without detectable cerebral infarction on MR imaging. This model allows evaluation of the effect of treatment on delayed vasospasm in the same animals. The canine double-hemorrhage model of SAH is suitable for the quantitative and chronological study of delayed angiographic vasospasm, but not for investigating early brain injury and delayed cerebral ischemia.

SAT0301 Vasospastic Severity and Digital Ischemia during Cooling is Related to Nail-Fold Capillaroscopic Pattern in Patients with Secondary Raynaud Phenomenon and Systemic Sclerosis

BackgroundMicroangiopathy, assessed as specific nail-fold capillaroscopic patterns (NCP), is a key feature and currently diagnostic criterion in the development of systemic sclerosis (SSc). In advanced SSc, NCP severity correlates clearly...

Abstract 210: A Phase I Clinical Trial of Sildenafil for the Treatment of Cerebral Vasospasm Following Subarachnoid Hemorrhage

Introduction: Animal studies have indicated that phosophodiesterase V (PDE-V) inhibition reduces cerebral vasospasm and improves outcomes following subarachnoid hemorrhage (SAH). Hypothesis: We hypothesize that sildenafil (an FDA-approved PDE-V inhibitor) is safe when given to patients with aneurysmal SAH and improves cerebral vasospasm. Methods: A prospective, non-randomized proof-of-principle trial using a two-phase dose escalation scheme was implemented. Patients with SAH underwent day-7 screening angiography to assess for vasospasm. In phase I, those with moderate to severe vasospasm were given 10mg (low dose) of intravenous sildenafil, followed by repeat angiography 30 mins after infusion. In phase II, patients with any degree of vasospasm were given 30mg (high dose) of sildenafil, followed by repeat angiography. Safety was assessed by analyzing vital signs, intracranial pressure (ICP) monitoring neurological status, and observing for the development of adverse reactions attributable to sildenafil. Two blinded reviewers compared pre- and post-sildenafil angiographic images to admission angiography and subjectively graded them as “improvement” or “no improvement” in vasospasm. Unblinded quantitative measurements of vessel diameter change were also made between pre- and post-sildenafil angiograms. Results: Eleven of 23 patients enrolled had vasospasm, received sildenafil and underwent repeat angiography (5 received the 10mg dose and 6 the 30mg dose). There were no adverse effects upon heart rate, ICP, or neurologic status. Sildenafil infusion did result in a transient decline in mean arterial pressure (MAP). With the low dose there was a 16% decline in MAP with an average time to return to baseline of 16 mins. For the high dose the decline was 19% with an average of 33 mins to return to baseline. Seven of 11 (64%) had angiographic improvement in vasospasm, with 3 of 5 (60%) from the low dose group and 4 of 6 (67%) from the high dose group. The average vessel dilatation in responders was 1.25 mm. Conclusions: Sildenafil is safe and well tolerated when given for the acute treatment of SAH-related cerebral vasospasm. These findings provide preliminary evidence that angiograpic vasospasm is improved in select patients following sildenafil infusion.

Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.

Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.

Correlation between asymmetric dimethylarginine and cerebral vasospasm secondary to subarachnoid hemorrhage

Objective To investigate the correlation between asymmetric dimethylarginine (ADMA) and cerebral vasospasm (CVS) secondary to subarachnoid hemorrhage (SAH).Methods Seventy-eight healthy male adult Sprague-Dawley rats were randomly allocated into control group (n =6),sham group (n =36) and SAH group (n =36).In SAH group,a SAH model was established by double autologous blood injection into cisterna magna.Arterial blood,cerebrospinal fluid (CSF) and basilar artery samples of each group were collected at the preconcerted time.ADMA levels in the plasma and CSF samples were assessed using enzyme-linked immuno sorbent assay (ELISA).Nitrite and nitrate concentrations were used as a marker of nitric oxide production in plasma and CSF samples and determined by using nitrate reductase method.Pathomorphological changes were observed with optical microscope and inner diameter of basilar artery was measured by Micrometer after hematoxylin-eosin staining was performed.Results (1) In SAH group,ADMA levels in CSF samples were significantly increased at 1st,3rd,5th and 7th day (P ＜0.05),and NO levels in CSF samples were significantly decreased at 3rd,5th,and 7th day as compared with sham group (P＜0.01).(2) The ratio of thickness and inner diameter of basilar artery was used to indicate the degree of CVS.The level of ADMA in CSF samples was strongly correlated with the degree of CVS (r =0.641,P ＜0.01).Nitrite levels in CSF samples were negatively correlated with ADMA levels in CSF samples (r =-0.687,P ＜0.01).(3) Plasma ADMA levels in sham group and SAH group were similar and remained essentially unchanged during the several days after SAH.Plasma ADMA levels were neither correlated with NO levels (r =0.019,P ＞ 0.05) nor with the degree of vasospasm (r =-0.046,P ＞ 0.05).Conclusion Asymmetric dimethylarginine reduces the level of nitric oxide in CSF by inhibiting nitric oxide synthase and may be involved in the progression of cerebral vasospasm.The level of ADMA in CSF samples was strongly correlated with the degree of CVS in SAH rats.There is no evident correlation between the level of ADMA in plasma and the degree of CVS. Key words: Subarachnoid hemorrhage; Cerebral vasospasm ; Asymmetric dimethylarginine ; Nitric oxide

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Objective: To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) in rats, in order to identify the initiating events, pathophysiological changes and potential targets for treatment. Methods: Twenty-eight male Sprague-Dawley rats (250 - 300 g) were arbitrarily assigned to one of two groups - SAH or saline control. Rat subarachnoid hemorrhage in the SAH group (n=15) was induced by double injection of autologous blood, 48 hr apart, into the cisterna magna. Similarly, normal saline (n=13) was injected into the cisterna magna of the saline control group. Rats were sacrificed on day five after the second blood injection and the brains were preserved for histological analysis. The degree of vasospasm was measured using sections of the basilar artery, by measuring the internal luminal cross sectional area using NIH Image-J software. The significance was tested using Tukey/Kramer's statistical analysis. Results: After analysis of histological sections, basilar artery luminal cross sectional area were smaller in the SAH than in the saline group, consistent with cerebral vasospasm in the former group. In the SAH group, basilar artery internal area (.056 μm ± 3) were significantly smaller from vasospasm five days after the second blood injection (seven days after the initial blood injection), compared to the saline control group with internal area (.069 ± 3; p=0.004). There were no mortalities from cerebral vasospasm. Conclusion: The rat double SAH model induces a mild, survivable, basilar artery vasospasm that can be used to study the pathophysiological mechanisms of cerebral vasospasm in a small animal model. A low and acceptable mortality rate is a significant criterion to be satisfied for an ideal SAH animal model so that the mechanisms of vasospasm can be elucidated 7, 8. Further modifications of the model can be made to adjust for increased severity of vasospasm and neurological exams.

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) in rats, in order to identify the initiating events, pathophysiological changes and potential targets for treatment. Twenty-eight male Sprague-Dawley rats (250 - 300 g) were arbitrarily assigned to one of two groups - SAH or saline control. Rat subarachnoid hemorrhage in the SAH group (n=15) was induced by double injection of autologous blood, 48 hr apart, into the cisterna magna. Similarly, normal saline (n=13) was injected into the cisterna magna of the saline control group. Rats were sacrificed on day five after the second blood injection and the brains were preserved for histological analysis. The degree of vasospasm was measured using sections of the basilar artery, by measuring the internal luminal cross sectional area using NIH Image-J software. The significance was tested using Tukey/Kramer's statistical analysis. After analysis of histological sections, basilar artery luminal cross sectional area were smaller in the SAH than in the saline group, consistent with cerebral vasospasm in the former group. In the SAH group, basilar artery internal area (.056 μm ± 3) were significantly smaller from vasospasm five days after the second blood injection (seven days after the initial blood injection), compared to the saline control group with internal area (.069 ± 3; p=0.004). There were no mortalities from cerebral vasospasm. The rat double SAH model induces a mild, survivable, basilar artery vasospasm that can be used to study the pathophysiological mechanisms of cerebral vasospasm in a small animal model. A low and acceptable mortality rate is a significant criterion to be satisfied for an ideal SAH animal model so that the mechanisms of vasospasm can be elucidated. Further modifications of the model can be made to adjust for increased severity of vasospasm and neurological exams.

Continuous intrathecal glyceryl trinitrate prevents delayed cerebral vasospasm in the single-SAH rabbit model in vivo

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of high morbidity and mortality. The reduced availability of nitric oxide (NO) in blood and cerebrospinal fluid (CSF) is well established as a key mechanism of vasospasm. Systemic administration of glyceryl trinitrate (GTN), an NO donor also known as nitroglycerin, has failed to be established in clinical settings to prevent vasospasm because of its adverse effects, particularly hypotension. The purpose of this study was to analyze the effect of intrathecally administered GTN on vasospasm after experimental SAH in the rabbit basilar artery. A single-hemorrhage model of SAH in rabbits was used to induce vasospasm. GTN (0.5 mg/ml) or saline was infused via a subcutaneous implanted osmotic pump with continuous drug release into the cerebellomedullary cistern over 5 days. The degree of vasospasm in the basilar artery was recorded with angiography on day 5 after SAH and was compared to baseline angiography on day 0. Significant reduction of basilar artery diameter was observed in the SAH group with saline infusion compared to sham-operated animals. Intrathecally administered GTN had no effect on the vessel diameter in sham-operated animals, whereas it significantly prevented vasospasm in the SAH group. Intrathecal GTN infusion did not affect arterial blood pressure. Prophylactic, continuous intrathecal administration of GTN prevents vasospasm of the basilar artery in the rabbit SAH model. No toxic effects could be demonstrated in this study. The clinical safety and feasibility of this strategy need to be further investigated.

脳血管攣縮 経時的３Ｄ‐ＣＴＡによる，くも膜下出血後の脳血管攣縮の評価

We assess the usefulness of serial three-dimensional CT angiography (CTA) in the diagnosis of cerebral vasospasm (VS), and evaluate the contribution of VS to symptomatic vasospasm (SVS), cerebral infarction, and modified Rankin scale (mRS) in patients with aneurysmal subarachnoid hemorrhage (SAH). Within 3 hours after the onset of symptoms, CTA was performed in 48 patients with SAH. CTA was repeated on Day 5-8 (median 7) and Day 12-15 (median 14) to assess VS. Vasospasm was defined as ≥25% vascular narrowing, and rated with the following criteria (degree of VS): moderate spasm (25-50% decrease in vessel diameter), and severe spasm (≥50% decrease). Vasospasm was also categorized as follows (CTA grade): no VS, local VS, and diffuse VS. By local VS we mean an area of narrowing of the vessel in continuity with an aneurysm and not extending more than 2 cm to the aneurysm, or limited to the A-1, A-2 portion (≤2 cm). Diffuse VS means any stenosis affecting either a long segment of vessel or distal segments of cerebral arteries. Aggressive treatments for the VS including triple H therapy were started, when either SVS was revealed or Diffuse VS was detected on CTA. We statistically investigate correlations of Hunt and Kosnik grade, Fisher CT group, degree of VS, and CTA grade, with SVS, cerebral infarction, and mRS. Of the 48 patients, 32 (67%) showed VS and 19 (40%) revealed SVS by the 3rd CTA. Cerebral infarction on CT was detected in 13 (27%) patients. With logistic regression analysis, CTA grade significantly correlated with SVS and infarction, while Hunt and Kosnik grade and age of the patients significantly correlated with mRS. Prospective evaluation of CTA following SAH might allow early recognition of VS and promote aggressive treatment and improved neurological outcomes.

Intraoperative angiography in aneurysm surgery: An initial experience

Intraoperative angiography (IOA) assumes an important role in the prevention of complications such as aneurysmal neck remnant or compromise of adjacent cerebral vasculature during surgery for cerebral aneurysms. Aims : To determine the feasibility, efficacy and safety of IOA in aneurysmal surgery. Prospective study of IOA in patients undergoing aneurysmal surgery. IOA was performed using digital subtraction angiography (DSA) compatible C-arm, radiolucent operating table and appropriate femoral sheath, guiding catheters and guide wires in 20 consecutive patients after surgical clipping of the cerebral aneurysm. The post-clipping IOA was compared with preoperative angiogram. Complete aneurysmal obliteration was confirmed in all the patients. In two patients compromization of adjacent vessels was noted, which could be rectified by repositioning of the clip. Some degree of vasospasm was noted in all the patients. Intra-arterial nimodipine was administered in four patients with severe vasospasm. There was improvement in two patients. Time taken for performing IOA varied from 30 to 45 min. No complications attributable to IOA were encountered in this study. IOA is a safe and effective adjunctive tool for aneurysm clipping. Routine use of IOA in all cases of aneurysmal surgery is recommended.

Attenuation of subarachnoid hemorrhage–induced apoptotic cell death with 17 beta-estradiol

Apoptosis is implicated in vasospasm and long-term sequelae of subarachnoid hemorrhage (SAH). The authors observed that 17beta-estradiol (E2) can attenuate cerebral vasospasm, lower endothelin-1 production, and preserve normal endothelial nitric oxide synthase expression by reduction of inducible NO synthase expression in experimental SAH. The authors investigated the potential antiapoptotic effects of E2 in an experimental rat model of SAH. The authors examined the antiapoptotic effects of E2 in a double-hemorrhage SAH model in male Sprague-Dawley rats. The rats underwent subcutaneous implantation of a Silastic tube containing corn oil either with or without E2, and some E2-treated animals also received ICI 182,780 (a nonselective estrogen receptor [ER] antagonist) for 7 days after SAH. The degree of vasospasm was determined by averaging the cross-sectional areas of the basilar artery 7 days after SAH. The expression of apoptotic indicators, including TNF-alpha, caspase 3, Bcl-2, Bax, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL), and cell death assays were used for detection of apoptosis. Treatment with E2 significantly attenuated SAH-induced vasospasm. Seven days after the induction of SAH, positive TUNEL-staining was seen, and DNA fragmentation was increased in the dentate gyrus. Increased TNF-alpha and cleaved caspase-3 protein expression and decreased Bcl-2 protein expression in the dentate gyrus were also observed. These changes were reversed with E2-treatment but not in the presence of ICI 182,780. However, the expression of Bax did not change after SAH either with or without E2 treatment. The authors found that E2 appears to confer an antiapoptotic effect that reduces secondary brain injury after SAH via estrogen receptor-dependent mechanisms. This finding provides support for possible future applications of E2 treatment for the reduction of secondary injury after SAH in patients.