Impact of Retrograde Cerebral Perfusion on Ascending Aortic and Arch Aneurysm Repair

Purpose. The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined.

Material and Methods. Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes).

Results. The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008).

Conclusion. Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch.     

Blood Flow Increase by Cervical Spinal Cord Stimulation in Middle Cerebral and Common Carotid Arteries

The effect of spinal cord stimulation (SCS) on cerebral blood flow (CBF) has, in the past, been evaluated by semiquantitative techniques, but has not been used to treat CBF diseases. The aim of this study was to assess the effect of cervical SCS on regional blood flow by both semiquantitative and quantitative methods. Thirty‐five patients with cervical SCS‐implanted devices were enrolled. The following parameters were measured before and after cervical SCS: systolic and diastolic velocity (cm/s) in the middle cerebral artery (MCA) by transcranial Doppler (TCD) and volume blood flow quantification (ml/min) in the common carotid artery (CCA) by color Doppler. During cervical SCS there was a significant and bilateral increase in systolic (21%) and diastolic (26%) velocity in the MCA and in CCA blood flow (50%). We conclude that cervical SCS increases blood flow in the middle cerebral artery and common carotid artery. The consistent increase supports the potential usefulness of cervical SCS as an adjuvant treatment for cerebral blood flow diseases.     

CLOTBUST: Design of a Randomized Trial of Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke

BACKGROUND: Intravenous tissue plasminogen activator (TPA) therapy can be monitored with 2 MHz transcranial Doppler (TCD). This article describes the design of CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), the first prospective international multicenter randomized clinical trial of noninvasive externally applied ultrasound to enhance systemic thrombolysis in human stroke. SUBJECTS: Patients with acute ischemic stroke eligible for intravenous TPA therapy within 3 hours of symptom onset who have detectable middle cerebral artery occlusion on a prebolus TCD are included in this trial. All patients receive standard 0.9 mg/kg TPA therapy. Patients are randomized (1:1) to either 2 hours of continuous monitoring with TCD or placebo monitoring. FDA-approved portable diagnostic TCD equipment and standard headframes (Marc series, Spencer Technologies, Seattle, WA) are used. Output of TCD units is set at 100% power achievable at depths of insonation that display the worst TIBI flow grade signals. METHODS AND END-POINTS: Acute MCA occlusion on prebolus TCD is defined as thrombolysis in brain ischemia (TIBI) flow grades 0-3. Treating physicians are blinded to randomization assignment, and certified scorers measure stroke severity using the National Institute of Health Stroke Scale (NIHSS). Safety of continuous TCD monitoring is determined by rates of symptomatic (NIHSS score increase by 4+ points) intracerebral hemorrhage within 72 hours after initial symptom onset. Potential enhancement of TPA therapy will be determined using combined primary end-point of early complete recanalization on TCD (TIBI flow grades 4-5), dramatic recovery (NIHSS < or = 3 points), or decline in the NIHSS > or = 10 points repeatedly measured every 30 minutes within 2 hours after TPA bolus. Other end-points include recovery at 24 hours and 3 months, modified Rankin scores (mRS) are obtained at 90 days, and favorable outcome is determined as NIHSS or mRS scores 0-1. CONCLUSIONS: The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.     

Functional decline in frail community-dwelling stroke patients

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.     

不同次数和剂量异丙酚预处理对大鼠全脑缺血再灌注损伤的作用

目的探讨不同次数和剂量异丙酚预处理对大鼠全脑缺血再灌注损伤的作用及其有关机制。方法176只雄性Wistar大鼠随机分为5组：假手术组(SH组,n=16)；缺血再灌注组(1组,n= 16)；异丙酚预处理1次组(P1组,n=48)；异丙酚预处理3次组(P3组,n=48)；异丙酚预处理5次组(P5组,n=48)。异丙酚预处理组又随机分为3个亚组：50 mg·kg~(-1)亚组、100 mg·kg~(-1)亚组、150 mg·kg~(-1)亚组(n=16)。P5组的各亚组在脑缺血前5d桉不同剂量腹腔注射异丙酚5d,容量不足5 ml者,用脂肪乳补足；P3组的各亚组注射脂肪乳2 d,异丙酚3 d；P1组的各亚组注射脂肪乳4d,异丙酚1d；SH组、Ⅰ组腹腔注射脂肪乳5 ml/d,共5 d。采用Pulsinelli-Brierley四血管闭塞法制备全脑缺血模型,全脑缺血20 min再灌注72h后,进行动物神经缺陷评分(NDS),随后断头取脑,观察海马CA1区神经元损伤程度的组织学分级(HG)、海马CA1区内未损伤的锥体细胞神经元密度(ND),原位末端标记法(TUNEL)检测凋亡细胞,计算凋亡指数(AI),原位杂交法测定海马脑源性神经营养因子(BDNF)mRNA及其受体酪氮酸激酶B(TrkB)mRNA的表达。结果1．除P1组的50 mg·kg~(-1)亚组外,其余各预处理组的ND、BDNF mRNA及TrkB mRNA表达均高于1组,NDS、HG和A1均低于Ⅰ组(P＜0．05)；2．与50 mg·kg~(-1)亚组相比,100mg·kg~(-1)、150mg·kg~(-1)亚组的ND、BDNF mRNA及TrkB mRNA表达均升高,NDS、HG和AI均降低(P＜0．05),100mg·kg~(-1)及150mg·kg~(-1)亚组间各指标差异无统计学意义(P＞0．05)；3．与PI组相比．P3组、P5组的ND、BDNF mRNA和TrkB mRNA表达均升高,NDS、HG和AI均降低(P＜0．05)．P3组、P5组间差异无统计学意义(P＞0．05)。结论异丙酚预处理可减轻大鼠全脑缺血再灌注损伤；在一定限度内,增加预处理次数和剂量可增强脑保护效果．其机制与BDNF和TrkB表达上调的程度有关。     

Computed tomographic changes of the brain and clinical outcome of patients with seizures and epilepsy after an ischaemic hemispheric stroke.

It is not well established whether seizures and epilepsy after an ischaemic stroke increase the disability of patients. Seventy-two patients with delayed seizures after a hemispheric infarct (37 with a single seizure and 35 with epilepsy) were included in the study. The modified Rankin scale was used to compare disability of the patients at 1 month after stroke and at 2 weeks after single or the last seizure, in case of epilepsy. The size of the X-ray hypoattenuation zone was compared on computed tomographic (CT) scans, performed in the weeks after the stroke and 1 week after single or repeated seizures. Lesion size was determined by superimposing the CT slices on digital cerebral vascular maps, on which the contours of the infarct area were delineated. The extent of the infarcts was expressed as the percentage fraction of the total surface area of the cerebral hemisphere. Groups with a single seizure and with epilepsy were mutually compared. Infarcts predominated in the parieto-temporal cortical regions. In the overall group the median Rankin score worsened significantly after seizures. The average size of the X-ray hypoattenuation zone was also significantly increased on the CT scans after the seizures, compared with those after stroke, without clear evidence of recent infarction. Mutual comparison of patients with a single seizure episode and of those with epilepsy showed only a trend of more severe disability and of increase in lesion size in the post-stroke epilepsy group. Delayed seizures and epilepsy after ischaemic stroke are accompanied by an increase in lesion size on CT and by worsening of the disability of the patients. This study does not allow to determine whether this is due to stroke recurrence or due to additional damage as a result of the seizures themselves.     

Comparison of Asymmetry in Cerebral Blood Flow Between Brain Hemispheres Using Digital Subtraction Angiography

BACKGROUND AND PURPOSE: Recently, endovascular techniques have gained significant therapeutic potential for both treatment and prevention of stroke. Cerebral angiography, which is an essential component of these procedures, has been used to provide morphological information regarding condition of blood vessels. In this study, we propose to determine the possibility of acquiring information regarding cerebral blood flow (CBF) in addition to morphologic information from data routinely available during angiography. METHODS: Digital subtraction angiography sequences were obtained for eight patients having occlusive disease in internal carotid artery (ICA) territories. Two regions-of-interest (ROIs) corresponding to the two brain hemispheres on AP view were delineated. For each image, the average pixel value within each ROI was calculated and used to generate time-density curves. Indices obtained from each curve were compared with each other and with the results obtained from the single photon emission computed tomography (SPECT) studies performed a pre- or postangiography procedure. RESULTS: Comparison between ICA stenosis and cerebral perfusion measurements revealed that cerebral perfusion deficit can be independent of arterial occlusive disease. The indices obtained from the time-density curves exhibit a correlating trend with the results from SPECT studies. However, lack of sufficient sample data prevented any meaningful statistical analysis to be conducted. CONCLUSIONS: We have developed a technique for utilizing the angiographic data for the important task of routinely and easily measuring CBF. Availability of CBF measurements during cerebral angiography may favorably impact upon the appropriate use of endovascular procedures and potentially contribute to the reduction of morbidity and mortality associated with stroke.     

醒脑静注射液治疗缺血性中风急性期随机对照试验的系统评价

目的 系统评价醒脑静注射液治疗缺血性中风急性期的疗效及安全性。方法 集醒脑静注射液治疗缺血性中风急性期随机对照试验文献，筛选合格研究，应用Jadad评分法进行质量评价，运用异质性检验、Meta-分析、漏斗图分析、敏感性分析等方法统计相关数据。结果 项研究符合纳入标准，Jadad评分所有研究得分均低于3分，属低质量文献。Meta-分析结果显示，总有效率比较的相对危险度（RR值）=1．04，99％的可信区间（CI值）为（0．88，1．23）。结论 前尚无充分证据证实醒脑静注射液治疗缺血性中风急性期的疗效及安全性。要进一步验证醒脑静注射液治疗缺血性中风急性期的疗效及安全性，尚需进行设计合理、执行严格、多中心大样本且随访时间足够的随机对照试验。     

Inflammatory biomarkers in blood of patients with acute brain ischemia

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.     

Effective pulmonary blood flow in children with acute asthma attack requiring hospitalization

In children with acute obstructive lung disease gas exchange is affected by ventilation-perfusion mismatch and the degree of bronchoconstriction. Standard lung function measurements do not reflect the impairment in gas exchange. Alternatively, the effective pulmonary blood flow (EPBF), that is, the proportion of the cardiac output that is supplying well-ventilated lung units, can give accurate and noninvasive estimates of ventilation-perfusion mismatch. We measured EPBF with the argon freon ?22 rebreathing technique in children with acute severe asthma to assess their response to nebulized salbutamol and to determine whether induced changes in the EPBF could be predicted from baseline measurements. Twenty-four children admitted with an acute asthma attack had spirometry and triplicate EPBF measurements before and after nebulized salbutamol. Eighteen patients had repeated tests 50 days later when fully recovered; 4 patients were taking methylxanthines on at least one occasion. The mean forced expiratory volume in 1 sec (FEV₁) rose from 55% of predicted to 66% after salbutamol and to 83% with recovery. The mean coefficients of variation for EPBF measurements on the three test occasions were 11.3%, 8.2%, and 9%. Except in children on methylxanthines, the EPBF values were reduced during the acute asthma attack (median, 2.53 L/min/m²; range, 1.99–3.60 L/min/m²) compared with paired values obtained after recovery (median, 2.89 L/min/m²; range, 2.2Eb4.04 L/min/m²) (P = 0.009). Salbutamol caused a highly significant increase in EPBF from 2.88 L/min/m² (range, 1.86–3.80) before treatment to 3.34 L/min/m² (range, 2.264.65) immediately afterwards (P = 0.0003). The spirometric indices did not relate to the changes in the EPBF values. However, when the effective stroke volume index was calculated in 11 patients, the changes induced by nebulized salbutamol had a significant inverse relation with the pretreatment FEV, (P = 0.61; P = 0.02). In conclusion, the argon freon-22 rebreathing technique can be used successfully and reproducibly to measure EPBF in children with an acute asthma attack. Except in children taking methylxanthines, EPBF during the acute attack is reduced and rises significantly after salbutamol. EPBF values after recovery were significantly higher than the presalbutamol values during the attack. Spirometric indices do not relate to the EPBF changes but are inversely related to the effective stroke volume changes. Pediatr Pulmonol. 1994; 17:370–377. © 1994 Wiley-Liss, Inc.