bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter Review of Preoperative Risk Factors for Endarterectomy for Asymptomatic Carotid Artery Stenosis
Authors: Goldstein Larry B. , Samsa Gregory P. , Matchar David B. , Oddone Eugene Z.
Published: June 2011

Background and Purpose
—The benefit of carotid endarterectomy is highly dependent on surgical risk. However, little data are available concerning factors affecting the risk of endarterectomy performed for asymptomatic carotid artery stenosis outside the setting of a randomized controlled trial. The purpose of this study was to analyze the impact of potential preoperative risk factors on the frequency of postoperative complications in patients undergoing the operation for asymptomatic disease in academic medical centers.

Methods
—Data regarding postoperative complications were systematically abstracted from the medical records of a random sample of patients who underwent carotid endarterectomy at 12 academic medical centers.

Results
—Of 1160 procedures reviewed, 463 (40%) were performed for asymptomatic disease. Postoperative stroke or death occurred in 13 (2.8%), and myocardial infarction occurred in 8 (1.7%). The rate of postoperative stroke or death was lower in asymptomatic patients than in those with a history of cerebrovascular symptoms in a different vascular distribution, but the difference was not significant (1.8% versus 4.2%;
P
=.21). There were no significant differences in these rates based on race, a history of angina, recent myocardial infarction, chronic obstructive pulmonary disease, hypertension, the degree of stenosis of the contralateral or ipsilateral carotid artery, or the presence of angiographically recognized ulceration, intraluminal thrombus, or siphon stenosis in the ipsilateral vessel (χ
2
;
P
>.05). Postoperative stroke or death was more frequent in women (5.3% versus 1.6% in men;
P
=.02), in those aged 75 years or older (7.8% versus 1.8% in those younger than 75 years;
P
=.01), and in those with a history of congestive heart failure (8.6% versus 2.3% in those without a history of congestive heart failure;
P
=.03). The risk of stroke or death was higher in the 16 patients who had carotid endarterectomy performed in combination with coronary artery bypass surgery than in those who had only endarterectomy (18.7% versus 2.1%;
P
<.001).

Conclusions
—The overall risk of postoperative stroke or death was nearly twice that reported by Asymptomatic Carotid Atherosclerosis Study (ACAS) investigators in the setting of a clinical trial but was within acceptable guidelines. Women were at higher postoperative risk than men, which supported ACAS findings. Additional high-risk groups were those aged 75 years or older, those with a history of congestive heart failure, and those undergoing prophylactic endarterectomy for asymptomatic stenosis in combination with coronary surgery. Knowledge of these rates may help to better assess an individual’s postoperative risk and therefore the anticipated benefit of surgery.
Distribution of
Chlamydia pneumoniae
Infection in the Atherosclerotic Carotid Artery
Authors: Yamashita Katsuhiro , Ouchi Kazunobu , Shirai Mutsunori , Gondo Toshikazu , Nakazawa Teruko , Ito Haruhide
Published: June 2011

Background and Purpose
—
Chlamydia pneumoniae
infection has recently become noteworthy in relation to atherosclerosis. We investigated by immunohistochemistry the distribution of
C pneumoniae
infection in the atherosclerotic carotid artery.

Methods
—Twenty carotid atherosclerotic lesions that were resected during carotid endarterectomy were investigated. Parallel sections were stained immunohistochemically with monoclonal antibodies for a
C pneumoniae
–specific antigen, macrophages, and smooth muscle cells.

Results
—Immunoreactivity for the
C pneumoniae
–specific antigen was observed in 11 of 20 specimens (55%), and intense immunoreactivity was observed in 7 of 20 (35%).
C pneumoniae
infection was observed in endothelial cells, macrophages and in smooth muscle cells that had migrated into the atheromatous plaque, as well as in smooth muscle cells and small arteries in the media underlying the atheromatous plaques.
C pneumoniae
infection was most prominently observed in smooth muscle cells. The severity of the infection as demonstrated by immunohistochemistry was not significantly related to general risk factors for atherosclerosis.

Conclusions
—
C pneumoniae
widely infects endothelial cells, macrophages, and smooth muscle cells in the atherosclerotic carotid artery. The results of the present study can help us to understand how
C pneumoniae
infection contributes to the progression of carotid atherosclerosis.
Inhibition of Poly(ADP-Ribose) Polymerase
Authors: Lo Eng H. , Bosque-Hamilton Prince , Meng Wei
Published: June 2011

Background and Purpose
—The nuclear enzyme poly(ADP-ribose) polymerase (PARP) may play a role in DNA repair. However, in cerebral ischemia, excessive PARP activation may lead to energy depletion and exacerbation of neuronal damage. We examined the effect of inhibiting PARP on (1) the degree of cerebral injury in a rat model of transient focal ischemia and (2) the degree of neurotransmitter dysregulation induced by local cortical perfusion of
N
-methyl-
d
-aspartate (NMDA).

Methods
—In experiment 1, rats were subjected to transient ischemia for 90 minutes by occlusion of the middle cerebral artery. After 22.5 hours of reperfusion, lesions were quantified by tetrazolium staining. Untreated rats were compared with those treated with the PARP inhibitor 3-aminobenzamide (10 mg/kg). In experiment 2, rats were implanted with microdialysis probes in the cortex, and 1 mmol/L NMDA was perfused for 2 hours. Extracellular concentrations of neurotransmitter and neuromodulator amino acids were measured. Untreated rats were compared with those given 10 mg/kg 3-aminobenzamide.

Results
—In experiment 1, PARP inhibition significantly reduced lesion volumes: 204±43 mm
3
(untreated) versus 90±24 mm
3
(treated). Neuroprotection was primarily manifested in the cortex. In experiment 2, NMDA perfusion resulted in large elevations of glutamate, taurine, and the lipid component phosphoethanolamine. Levels of the NMDA site modulator
d
-serine were reduced, and glycine levels appeared unchanged. 3-Aminobenzamide significantly attenuated the elevations in glutamate and phosphoethanolamine but had no effects on
d
-serine and glycine.

Conclusions
—Inhibition of PARP reduced injury after transient focal ischemia in rats and attenuated NMDA-induced glutamate efflux and overall neurotransmitter dysregulation. The deleterious effects of excessive PARP activation may be related in part to amplification of excitotoxicity, possibly by cellular energy depletion and additional transmitter release and/or reduced reuptake.
Cervical Carotid Artery Vasospasms Causing Cerebral Ischemia
Authors: Arning Christian , Schrattenholzer Alexandra , Lachenmayer Lutz
Published: June 2011

Background
—The etiology of cerebral ischemic accidents in young adults often remains unclarified.

Case Description
—A 32-year-old woman presented after multiple episodes of left monocular visual impairment and right-sided focal signs. MRI revealed a low-flow infarction on the left; color-coded duplex sonography (CCDS), however, showed normal vascular findings. During the inpatient rehabilitation, a renewed visual impairment occurred; an immediate CCDS examination now demonstrated a filiform stenosis of the left internal carotid artery (ICA) 4 cm above the origin and indirect signs of a severe stenosis of the right ICA. Results of a follow-up examination 18 hours later were again normal. Six weeks later, on reoccurrence of visual impairment, a reversible stenosis of the left ICA was again demonstrated. A search for possible causes of vasospasm was unsuccessful. After treatment with calcium antagonists the patient was free of complaints (with the exception of 3 very short attacks of visual impairment) during the following 12 months.

Conclusions
—Cervical carotid artery vasospasms can apparently occur spontaneously without a mechanical trigger. Because their detection is difficult, vasospasms may go undetected.
Diagnostic Impact and Prognostic Relevance of Early Contrast-Enhanced Transcranial Color-Coded Duplex Sonography in Acute Stroke
Authors: Goertler Michael , Kross Regina , Baeumer Matthias , Jost Stefan , Grote Reinhard , Weber Sepp , Wallesch Claus-Werner
Published: June 2011

Background and Purpose
—We sought to evaluate the diagnostic value of echo-enhanced transcranial color-coded duplex sonography (TCCD) and the clinical relevance of vascular pathology assessed by sonography for early clinical outcome in acute ischemic stroke.

Methods
—We present 23 consecutive patients with an anterior circulation stroke in whom clinical examination, CT, and ultrasonography were performed within 5 hours after the onset of symptoms. Transcranial Doppler sonography (TCD) and unenhanced and contrast-enhanced TCCD (Levovist, 4 g, 300 mg/mL) were compared for their ability to detect middle cerebral artery (MCA) occlusion and flow velocity reduction suggesting hemodynamic impairment in the MCA distribution pathway. Sonographic examination times were registered. Baseline clinical characteristics and CT findings were assessed. Neurological deficit was quantified according to the National Institutes of Health Stroke Scale score, with an early clinical improvement defined as decrease of the score by 4 or more points or a complete resolution of the deficit on day 4.

Results
—Contrast-enhanced TCCD enabled diagnosis of intracranial vascular pathology in 20 affected hemispheres, whereas unenhanced TCCD and TCD were conclusive in 7 and 14 hemispheres, respectively (
P
=0.0001). Contrast-enhanced TCCD was superior in evaluating distal carotid (carotid-T) occlusion and differentiating major vessel occlusions from patent arteries with flow velocity diminution. Mean examination time for enhanced TCCD ranged from 5 to 7 minutes, depending on the number of investigated vessels (without or with MCA branches). Logistic regression selected a patent MCA without reduced blood flow velocity as the only independent predictor for an early clinical improvement (
P
<0.01).

Conclusions
—Contrast-enhanced TCCD is a promising tool for early prognosis in anterior circulation stroke. It is considered superior to unenhanced TCCD and TCD.
Effects of Acetazolamide on Choroidal Blood Flow
Authors: Dallinger Susanne , Bobr Barbara , Findl Oliver , Eichler Hans-Georg , Schmetterer Leopold
Published: June 2011

Background and Purpose
—The acetazolamide provocation test is commonly used to study cerebrovascular vasomotor reactivity. On the basis of the effect of a carbonic anhydrase inhibitor in the central nervous system, we hypothesized that acetazolamide may also increase blood flow in the human choroid.

Methods
—In a placebo-controlled, randomized, double-blind, three-way crossover design, acetazolamide (500 mg or 1000 mg IV) or placebo was administered to nine healthy subjects. The effect of acetazolamide was studied at 15-minute intervals for 90 minutes. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity and resistive index in the ophthalmic artery were measured with Doppler sonography. In a second study in six healthy subjects, we assessed the effect of acetazolamide (1000 mg IV) on intraocular pressure.

Results
—Acetazolamide increased fundus pulsation amplitude in a dose-dependent manner (1000 mg: +33%; 500 mg: +20%;
P
<0.001, ANOVA). The effect of acetazolamide on MFV (1000 mg: +18%; 500 mg: +8%;
P
=0.003, ANOVA) and RI (1000 mg: −4%; 500 mg: −2%;
P
=0.006, ANOVA) was less pronounced but also significant. Acetazolamide did not induce any changes in systemic hemodynamic parameters but significantly decreased intraocular pressure (1000 mg: −37%;
P
<0.0001).

Conclusions
—The present data show for the first time that intravenously administered acetazolamide increases choroidal blood flow in humans. This phenomenon therefore indicates that the acetazolamide provocation test may qualify as a tool to investigate ocular vasomotor reactivity in a variety of ocular diseases. Moreover, the increase in choroidal blood flow after carbonic anhydrase inhibition can be expected to contribute to the therapeutic efficacy of carbonic anhydrase inhibitors in glaucoma.
A New Approach to Retrain Gait in Stroke Patients Through Body Weight Support and Treadmill Stimulation
Authors: Visintin Martha , Barbeau Hugues , Korner-Bitensky Nicol , Mayo Nancy E.
Published: June 2011

Background and Purpose
—A new gait training strategy for patients with stroke proposes to support a percentage of the patient’s body weight while retraining gait on a treadmill. This research project intended to compare the effects of gait training with body weight support (BWS) and with no body weight support (no-BWS) on clinical outcome measures for patients with stroke.

Methods
—One hundred subjects with stroke were randomized to receive one of two treatments while walking on a treadmill: 50 subjects were trained to walk with up to 40% of their body weight supported by a BWS system with overhead harness (BWS group), and the other 50 subjects were trained to walk bearing full weight on their lower extremities (no-BWS group). Treatment outcomes were assessed on the basis of functional balance, motor recovery, overground walking speed, and overground walking endurance.

Results
—After a 6-week training period, the BWS group scored significantly higher than the no-BWS group for functional balance (
P
=0.001), motor recovery (
P
=0.001), overground walking speed (
P
=0.029), and overground walking endurance (
P
=0.018). The follow-up evaluation, 3 months after training, revealed that the BWS group continued to have significantly higher scores for overground walking speed (
P
=0.006) and motor recovery (
P
=0.039).

Conclusions
—Retraining gait in patients with stroke while a percentage of their body weight was supported resulted in better walking abilities than gait training while the patients were bearing their full weight. This novel gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke.
Role of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Endotoxin-Induced Cerebral Hyperemia
Authors: Okamoto Hirotsugu , Ito Osamu , Roman Richard J. , Hudetz Antal G.
Published: June 2011

Background and Purpose
—Bacterial lipopolysaccharide (LPS), an endotoxin, has been reported to induce the expression of inducible isoforms of both nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in various cell types. LPS is also known to dilate systemic vasculature, including cerebral vessels. This study aimed to determine to what extent LPS induces iNOS and COX-2 expression in the brain and whether NO and/or cyclooxygenase metabolites derived from iNOS and/or COX-2 contribute to the LPS-induced cerebral hyperemia.

Methods
—Regional cerebral blood flow (rCBF) was measured by laser-Doppler flowmetry in halothane-anesthetized, artificially ventilated rats for 4 hours after intracerebroventricular administration of LPS.

Results
—LPS at doses of 0.01 mg/kg to 1 mg/kg caused dose-dependent, progressive increases in rCBF at 1 to 4 hours after administration. The increase in rCBF was attenuated by systemic administration of the selective iNOS inhibitor aminoguanidine (100 mg/kg IP) or the selective COX-2 inhibitor NS-398 (5 mg/kg IP), and it was abolished by preventing induction of these isoforms with dexamethasone (4 mg/kg IP). LPS significantly increased iNOS and COX-2 mRNA, iNOS protein, and iNOS and cyclooxygenase enzyme activity. The increases in iNOS and cyclooxygenase enzyme activity were eliminated by aminoguanidine and NS-398, respectively. Dexamethasone also prevented the increase in iNOS and cyclooxygenase activity.

Conclusions
—These results indicate that induction of iNOS and COX-2 expression and the increased production of NO and vasodilator prostanoids in the brain contribute to the elevation in CBF after intracerebroventricular administration of LPS.
Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage
Authors: Osuka Koji , Suzuki Yoshio , Watanabe Yasuo , Takayasu Masakazu , Yoshida Jun
Published: June 2011

Background and Purpose
—Inducible cyclooxygenase (COX-2) has been found to play a pathological role in cerebral insult
.
We investigated the expression of COX-2 in the basilar artery after experimental subarachnoid hemorrhage (SAH).

Methods
—In a canine “two-hemorrhage” model of SAH, the basilar arteries were obtained on day 2 after a cisternal injection of autologous blood or on days 4, 6, 7, or 9 after the second injection. Basilar arteries also were obtained 12 hours after intracisternal injection a cytokine: interleukin (IL)-1β (0.03 μg), IL-6 (3 μg), or IL-8 (10 μg). Western blotting with a polyclonal anti–COX-2 antibody was performed in these arteries.

Results
—COX-2 protein was not demonstrated in the basilar artery in control animals without SAH. However, it was expressed in the basilar artery on days 2, 4, 6, and 7 after blood injection but not on day 9
.
Intracisternal injection of IL-1β, IL-6, or IL-8 also induced COX-2 in the basilar artery.

Conclusions
—COX-2 expression was detected in basilar arterial tissue in both acute and chronic stages after SAH. Elevation of inflammatory cytokines after SAH may be involved in the induction of COX-2, which may produce sufficient quantities of eicosanoids to affect hemodynamics after SAH.
Posthyperventilatory Steal Response in Chronic Cerebral Hemodynamic Stress
Authors: Nariai Tadashi , Senda Michio , Ishii Kenji , Wakabayashi Shinichi , Yokota Takanori , Toyama Hinako , Matsushima Yoshiharu , Hirakawa Kimiyoshi
Published: June 2011

Background and Purpose
—The alteration of regional cerebral blood flow (CBF) during and after hyperventilation was measured using positron emission tomography (PET) to determine the circulatory response induced by daily respiratory changes in the cerebral area under chronic hemodynamic stress.

Methods
—Three normal volunteers and 12 patients with an obstruction of major cerebral arteries underwent PET measurements of the CBF after an injection of H
2
15
O: (1) in the resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO
2
, and (5) after an injection of acetazolamide. Eleven patients also underwent a
15
O gas study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume (CBV).

Results
—(1) In 9 patients, the CBF value in the post-HV scan was lower than that in the HV scan in 1 or more regions in the area of the obstructed arteries, although the Pa
co
2
level during the post-HV scan was higher than that during the HV scan in all patients. All control regions in the patients and in the normal volunteers showed an elevated CBF in the post-HV scan compared with the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was prominent in 4 patients with moyamoya vessels and in another 5 patients with atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV or OEF). (3) The regional pre- to post-HV change in CBF was significantly correlated with the CBF responses to acetazolamide and CO
2
.

Conclusions
—Vasodilatation after the termination of hyperventilation in the normal areas induces a steal response in the cerebral area suffering from hemodynamic stress and may cause profound hypoperfusion in everyday situations. This phenomenon may be important to our understanding of the clinical symptoms and the natural course of chronic cerebral occlusive disease bearing hemodynamic stress.
Risk Factors for Ischemic Stroke
Authors: Simons Leon A. , McCallum John , Friedlander Yechiel , Simons Judith
Published: June 2011

Background and Purpose
—One in 10 deaths in Australia is due to stroke. The predictors of ischemic stroke have not been well defined, although hypertension, atrial fibrillation, and previous stroke have been consistently reported. We report on 98 months’ follow-up in a prospective study of cardiovascular disease in the Australian elderly, the Dubbo Study.

Methods
—The cohort, first examined in 1988, was composed of 2805 men and women 60 years and older. The prediction of ischemic stroke by potential risk factors was examined in a Cox proportional hazards model, after linkage to hospital and death records.

Results
—Three hundred six men and women manifested an ischemic stroke event (ICD-9-CM 433 to 437), and 95 subjects suffered a fatal stroke event. In the multivariate model, the significant independent predictors of stroke were advancing age, female sex (48% lower risk), being married (30% lower risk), prior history of stroke (227% higher risk), use of antihypertensive drugs (37% higher risk), belonging to the highest category of blood pressure reading (67% higher risk), presence of atrial fibrillation (58% higher risk), HDL cholesterol (36% lower risk for each 1-mmol/L increment), impaired peak expiratory flow (77% higher risk for tertile I than for tertile III), physical disability (59% higher risk), and depression score (41% higher risk for tertile III than for tertile I).

Conclusions
—These findings suggest that morbidity and mortality associated with ischemic stroke can be predicted by various clinical indicators, some of which may be amenable to intervention. The matters of impaired peak expiratory flow, depression score, and ischemic stroke require further study.
Opposing National Stroke Mortality Trends in Poland and for African Americans and Whites in the United States, 1968 to 1994
Authors: Massing Mark W. , Rywik Stefan L. , Jasinski Bogdan , Manolio Teri A. , Williams O. Dale , Tyroler Herman A.
Published: June 2011

Background and Purpose
—The United States (US) has experienced declines in stroke mortality in contrast to the increases reported for Poland. As part of the Poland and US Agreement on Cardiovascular and Cardiopulmonary Research, stroke mortality trends in Polish and US subpopulations were compared in the context of cross-population differences in competing causes of death and determinants of stroke.

Methods
—Age-adjusted annual stroke, cardiovascular disease (CVD), non-CVD, and all-cause mortality rates were determined for men and women aged 35 to 64 and 65 to 74 years from 1968 to 1994 for African Americans and US whites and in Poland. Mean annual percent changes of mortality rates were estimated during 1968 to 1980 and 1981 to 1994 with the use of piecewise log-linear regression.

Results
—US stroke mortality rates declined 3.7% to 4.8% annually during 1968 to 1980 and 2.0% to 3.1% during 1981 to 1994, with similar declines in each ethnic, gender, and age group. Polish rates increased 3.3% to 5.5% annually for all age-gender groups in Poland during 1968 to 1980. Polish men aged 35 to 64 experienced increasing rates during 1981 to 1994 (1.6% annually), while Polish women and older men experienced slight declines or little change. Only Polish men aged 35 to 64 years exhibited increases in stroke, CVD, and non-CVD mortality rates during both time intervals.

Conclusions
—Poland and the US experienced opposing stroke mortality rate trends between 1968 and 1994. These national and ethnic trends occurring in just one generation suggest major effects of lifestyle, socioenvironmental, and/or medical care determinants.
ACE, MTHFR, Factor V Leiden, and APOE Polymorphisms in Patients With Vascular and Alzheimer’s Dementia
Authors: Chapman Joab , Wang Ningshan , Treves Therese A. , Korczyn Amos D. , Bornstein Natan M.
Published: June 2011

Background and Purpose
—There is a growing interest in the use of genetic markers in the differential diagnosis of dementia. In the current study we examined the usefulness of genetic risk factors for vascular disease as markers for vascular dementia (VD).

Methods
—The groups included 41 patients with VD, 49 patients with dementia of the Alzheimer’s type, and 40 age-matched control subjects without dementia. These patients were genotyped for vascular disease–associated polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), factor V Leiden (FVL), and a common genetic risk factor for AD, apolipoprotein E ε4 (APOE ε4).

Results
—There was no significant association between ACE, MTHFR, and FVL genotypes with VD whether compared with subjects with AD or with control subjects. There was a higher frequency of APOE ε4 alleles in patients with AD (30%,
P
=0.016) and VD (26%,
P
=0.07) compared with control subjects (15%).

Conclusions
—VD is not associated with the genetic risk factors for vascular disease examined in this study, indicating that the pathogenesis of VD may differ from other vascular diseases.
Stress-Induced Pulse Pressure Change Predicts Women’s Carotid Atherosclerosis
Authors: Matthews Karen A. , Owens Jane F. , Kuller Lewis H. , Sutton-Tyrrell Kim , Lassila Holly C. , Wolfson Sidney K.
Published: June 2011

Background and Purpose
—Individuals who exhibit large increases in blood pressure and heart rate during mental stress may be at risk for accelerated atherosclerosis. This report evaluates the association between stress-induced hemodynamic responses and carotid atherosclerosis in 254 healthy postmenopausal women.

Methods
—The magnitude of change in blood pressure and heart rate from rest to public speaking and mirror image tracing, two stressful tasks, was measured. Average intima-media thickness (IMT) and focal plaque in the common carotid artery, bulb, and internal carotid artery were measured with the use of duplex ultrasonography on average 2.3 years later.

Results
—The average IMT was 0.77 mm, with a range of 0.60 to 1.37; 52.5% had at least one plaque. Correlational analysis showed that greater IMT was associated with greater pulse pressure change during mental stress (
r
=0.17,
P
<0.01). Statistical adjustments for possible confounders (age, hormone replacement therapy use, resting pulse pressure, smoking status, and triglyceride levels) did not alter the results. The plaque index was associated with greater pulse pressure change during the mirror image tracing task (odds ratio=1.47,
P
=0.01) for women with a plaque score of ≥2 versus 1 or 0, adjusted for possible confounders.

Conclusions
—Mental stress–induced pulse pressure changes may influence the development of early atherosclerosis in the carotid artery of women. Widening of pulse pressure during stress, as well as at rest, may be a marker of compromised compliance in the vessel wall.
Effects of a Synthetic Allosteric Modifier of Hemoglobin Oxygen Affinity on Outcome From Global Cerebral Ischemia in the Rat
Authors: Grocott Hilary P. , Bart Robert D. , Sheng Huaxin , Miura Yoshihide , Steffen Robert , Pearlstein Robert D. , Warner David S.
Published: June 2011

Background and Purpose
—Neuronal injury results from an insufficient supply of oxygen to the brain. This experiment examined whether a pharmacologically induced rightward shift of the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) would improve outcome from either incomplete and/or near-complete forebrain ischemia–induced hypoxia in the rat.

Methods
—For incomplete ischemia (attenuated electroencephalogram), fasted rats (n=17 to 19 per group) were given a synthetic allosteric modifier of hemoglobin affinity for oxygen (RSR13; 150 mg/kg IV) before or immediately after 20 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 40 mm Hg. For near-complete ischemia (isoelectric electroencephalogram), rats (n=15 per group) were given RSR13 (150 mg/kg) at onset of reperfusion after 10 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 30 mm Hg. In both experiments, control rats were given vehicle (0.9% NaCl IV) only. Outcome (defined as percent dead hippocampal CA1 neurons) was determined at 5 days after ischemia.

Results
—RSR13 (150 mg/kg) produced a 68% rightward shift of P50 (34±3 to 57±8 mm Hg). RSR13 reduced CA1 damage resulting from incomplete ischemia by 28% (
P
=0.02), but only when administered at the onset of reperfusion. RSR13 had no effect on outcome from near-complete ischemia.

Conclusions
—A postischemic pharmacologically induced increase in P50 may improve outcome from incomplete global cerebral ischemia. More severe (near-complete) ischemia negates this benefit.
Two-Kidney, Two Clip Renovascular Hypertensive Rats Can Be Used as Stroke-prone Rats
Authors: Zeng Jinsheng , Zhang Yiqin , Mo Jianwei , Su Zhenpei , Huang Ruxun
Published: June 2011

Background and Purpose
—The cerebrovascular lesions in stroke-prone spontaneously hypertensive rats are not only dependent on high blood pressure but partly related to pressure-independent genetic factors. The aim of the present study was to observe whether spontaneous stroke occurred in renovascular hypertensive rats without a genetic deficiency.

Methods
—The 1-kidney, 1 clip (1k1c); 2-kidney, 1 clip (2k1c); and 2-kidney, 2 clip (2k2c) methods were used to induce hypertension in male Sprague-Dawley rats with a ring-shaped silver clip. Sham-operated rats were used as controls. Blood pressure and neurological symptoms were observed in the rats without any artificial inducement. Brain sections stained with hematoxylin-eosin and phosphotungstic acid–hematoxylin were examined under a microscope to determine stroke foci.

Results
—The attack rate of stable hypertension was 100% (55/55) in the 2k2c group, which was significantly higher than that in the 1k1c (23/30, 76.7%) and 2k1c (21/30, 70%) groups (
P
<0.01). None of the rats in the 2k2c group died of acute renal failure or suffered from diffuse cerebral lesions postoperatively. Forty weeks after renal artery constriction, the incidence of spontaneous stroke in the 2k2c group was 61.8% (34/55), which was significant higher than that in the 1k1c (7/30, 23.3%) and 2k1c (5/30,16.7%) groups (
P
<0.01). Stroke foci were not observed in normotensive controls.

Conclusions
—We conclude that 2k2c renovascular hypertensive rats with proper renal artery constriction can be used as stroke-prone renovascular hypertensive rats independent of a genetic deficiency.
Cost-Effectiveness of Anticoagulation in Nonrheumatic Atrial Fibrillation in the Primary Prevention of Ischemic Stroke
Authors: Lightowlers Sara , McGuire Alistair
Published: June 2011

Background and Purpose
—A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation.

Methods
—We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature.

Results
—The cost per life-year gained free from stroke over 10 years ranged from −£400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to £13 221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring.

Conclusions
—For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.
Hyperinsulinemia and the Risk of Stroke in Healthy Middle-Aged Men
Authors: Pyörälä Marja , Miettinen Heikki , Laakso Markku , Pyörälä Kalevi
Published: June 2011

Background and Purpose
—Several studies have shown that hyperinsulinemia is associated with the risk of coronary heart disease, but information on the association of hyperinsulinemia with the risk of stroke is limited. We investigated the association of hyperinsulinemia with the risk of stroke during a 22-year follow-up of the Helsinki Policemen Study population.

Methods
—The study was based on a cohort of 970 men aged 34 to 64 years who were free of cerebrovascular disease, other cardiovascular disease, or diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the insulin response curve during oral glucose tolerance test was used as a composite variable reflecting plasma insulin levels.

Results
—During the 22-year follow-up, 70 men had a fatal or nonfatal stroke. Hyperinsulinemia (highest area under the insulin response curve quintile compared with the combined 4 lower quintiles) was associated with the risk of stroke (age-adjusted hazard ratio, 2.12; 95% CI, 1.28 to 3.49), but not independently of other risk factors (multiple-adjusted hazard ratio, 1.54; 95% CI, 0.90 to 2.62), which was mainly due to the impact of obesity, particularly upper body obesity, with subscapular skinfold thickness used as an index. Of other risk factors, upper body obesity, blood pressure, and smoking were independent predictors of the risk of stroke.

Conclusions
—Hyperinsulinemia was associated with the risk of stroke in Helsinki policemen during the 22-year follow-up, but not independently of other risk factors, particularly upper body obesity.
Local Intra-Arterial Thrombolysis in Acute Ischemic Stroke
Authors: Gönner Friedrich , Remonda Luca , Mattle Heinrich , Sturzenegger Matthias , Ozdoba Christoph , Lövblad Karl-Olov , Baumgartner Ralf , Bassetti Claudio , Schroth Gerhard
Published: June 2011

Background and Purpose
—We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome.

Methods
—Forty-three patients were treated with LIT using urokinase (median dose, 0.75×10
6
IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death.

Results
—Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (
P
<0.001), improvement by 4 or more points on NIHSS score within 24 hours (
P
=0.001), and vessel recanalization (
P
=0.02). Recanalization was more likely if LIT was started within 4 hours (
P
=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%).

Conclusions
—LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.
Endothelial Nitric Oxide Synthase Exon 7 Polymorphism, Ischemic Cerebrovascular Disease, and Carotid Atheroma
Authors: Markus Hugh S. , Ruigrok Ynte , Ali Nadira , Powell John F.
Published: June 2011

Background and Purpose
—The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in exon 7 of the eNOS gene (894G→T) has been reported to be a strong risk factor for coronary artery disease. We determined whether it was also a risk factor for transient ischemic attack (TIA) and ischemic stroke and for carotid atheroma.

Methods
—We studied 361 consecutive white patients presenting with ischemic stroke or TIA to a neurological cerebrovascular disease service and 236 normal white controls. In all patients CT and/or MR head imaging and high-resolution carotid duplex ultrasound were performed. The presence of the polymorphism (N/n) was determined by polymerase chain reaction and restriction with the enzyme
Ban
II.

Results
—There was no difference in the frequency of the
NN
genotype between patients and controls (13.0% versus 15.3%;
P
=0.44) or in N allele frequency (39% versus 37%;
P
=0.57). There was no association with genotype when only patients with stroke (excluding those with TIA) or when only individuals aged ≤65 years were considered. In contrast, there was a highly significant independent association between cerebrovascular disease and hypertension (odds ratio, 2.87; 95% CI, 2.0 to 4.15;
P
<0.00001), smoking (odds ratio, 2.58; 95% CI, 1.80 to 3.70;
P
<0.00001), and diabetes (odds ratio, 2.68; 95% CI, 1.38 to 5.24;
P
=0.004). There was no relationship between the polymorphism and any particular stroke subtype: large-vessel disease, for
NN
, 15 of 105 (14.3%); lacunar disease, 10 of 75 (13.3%); cardioembolic and unknown, 18 of 151 (11.9%); and tandem pathology, 4 of 30 (13.3%) (
P
=0.68, χ
2
). There was no difference in the mean degree of carotid stenosis between the 3 genotypes:
NN,
31.1% (SD, 27.1);
Nn,
30.1% (29.0); and
nn
, 31.2% (26.3) (
P
=0.9). There was no association between the
NN
genotype or the N allele and hypertension.

Conclusions
—We failed to find a relationship between this exon 7 polymorphism and ischemic cerebrovascular disease. In particular, it was not associated with stroke and TIA secondary to large-vessel atherosclerosis or with the degree of carotid stenosis in patients with cerebrovascular disease. It is unlikely that this particular polymorphism or any closely linked polymorphism is a major risk factor in the majority of white patients with stroke.
Intracerebral Hemorrhage in the Rat: Effects of Hematoma Aspiration
Authors: Altumbabic Mensura , Peeling James , Del Bigio Marc R.
Published: June 2011

Background and Purpose
—Deep intracerebral hemorrhage is associated with considerable mortality and morbidity, but the value of surgical therapy is debatable. The purpose of this study was to evaluate whether aspiration of the hematoma in a rodent model of intracerebral hemorrhage could improve final neurological outcome.

Methods
—Intracerebral hemorrhage was induced in 2 groups of rats by injection of bacterial collagenase into the caudate nucleus. In 1 group of rats, streptokinase was used to lyse the hematoma 4 hours after hemorrhage induction, and the clot was then aspirated. Behavioral function was evaluated repeatedly until the rats were killed 7 weeks after collagenase injection. Histology was used to assess neuronal loss, astroglial proliferation, and overall brain morphology. In a second experiment, brain water was measured at 24 hours.

Results
—The treated rats performed significantly better than controls on a motor-behavior evaluation on days 1, 2, and 28 after aspiration. Skilled forelimb testing performed for 3 weeks after the global behavior evaluations showed a significant deficit of contralateral forelimb function in both groups, but there was no significant difference between the 2 groups. Neuronal loss in the perihematoma striatum was significantly greater in untreated compared with treated rats. In most rats, structural damage extended into the internal capsule and thalamus.

Conclusions
—Aspiration of the hematoma after collagenase-induced hemorrhage slightly improved acute functional outcome and reduced neuronal loss from the striatum. Further studies are required to delineate the mechanism of the effect.
Mechanisms of Motor Dysfunction After Transient MCA Occlusion: Persistent Transmission Failure in Cortical Synapses Is a Major Determinant
Authors: Bolay Hayrunnisa , Dalkara Turgay
Published: June 2011

Background and Purpose
—Failure of prompt motor recovery after spontaneous recirculation or thrombolytic therapy may be due to an unsatisfactory restoration of synaptic activity within cortex and/or blockade of electrical impulses at the severely ischemic subcortical region.

Methods
—Afferent, efferent, and synaptic activities were focally examined within the rat sensorimotor cortex by recording the somatosensory-evoked potential (SEP) and motor area response evoked by stimulation of premotor afferents (PmEP) intracortically and the motor-evoked potential (MEP) generated by stimulation of the forelimb area from the brain stem. The effect of ischemia on electrical activity in the cortex and on axonal conduction in the subcortical region was studied differentially by proximal or distal occlusion of the MCA.

Results
—MEP consisted of direct and indirect waves generated by direct activation of pyramidal axons and indirect excitation of pyramidal neurons via cortical synapses, respectively. MEP, PmEP, and SEP disappeared on proximal occlusion. Following reperfusion after 1 to 3 hours of ischemia, the direct wave of MEP readily recovered but the indirect wave showed no improvement, suggesting a restored axonal conduction but impaired cortical synaptic transmission. The synaptic defect, which also caused a poor recovery in PmEP and SEP and on electrocorticogram, was persistent and detected 24 hours after 1 hour of proximal occlusion.

Conclusions
—Our data suggest that motor dysfunction is caused by loss of cortical excitability and blockade of motor action potentials at the subcortical level during ischemia. After brief transient ischemia, axonal conduction readily recovers; however, a persistent transmission failure at cortical synapses leads to motor dysfunction.
Rapid Microvascular Repair Using Plastic Adhesive
Authors: Shintani Akira , Zervas Nicholas T. , Kuwayama Akio
Published: June 2011

Simple longitudinal arteriotomy was carried out in rabbits to assess the use of a rapid-setting tissue adhesive in shortening the time necessary to carry out microvascular repair. The vessels studied varied from 0.8 to 1.5 mm in diameter and repair was carried out using microsurgical dissection. It was found that the use of the tissue adhesive in conjunction with three sutures would bring about satisfactory repair of the arteriotomy for shortening the time of repair by at least 50%. Toxic reactions or other complications common to micro-anastomosis of small vessels were not encountered with any greater frequency than in controls.
Relationships Between Cerebral Perfusion Pressure and Regional Cerebral Blood Flow in Patients With Severe Neurological Disorders
Authors: HEILBRUN M. PETER , JORGENSEN PAUL BALSLEV , BOYSEN GUDRUN
Published: June 2011

Three patients, one with a recurrent brain tumor, one with a severe brain contusion, and one with a brain abscess, are described who had continuous monitoring of the intracranial pressure with epidural and/or ventricular pressure transducers, continuous monitoring of the blood pressure, and periodic regional cerebral blood flow (rCBF) studies by the intra-arterial
133
Xenon method. A fourth patient with a severe brain contusion is described who had only blood pressure monitoring and rCBF studies. By measuring the regional cerebral blood flow and by testing autoregulation through changes in cerebral perfusion pressure and arterial P
CO
2
, it is possible to reveal critical levels of cerebral perfusion pressure in the supratentorial compartment. Such measurements allow more rational evaluation of methods for control of increased intracranial pressure. The data point out that monitoring of systemic cardiorespiratory parameters for signs of cerebral compression is generally inadequate. The fact that pressure gradients may exist within the craniospinal enclosure is discussed. For this reason, before valid conclusions can be made regarding brain stem circulatory impairment at the tentorium and in the posterior fossa, the present regional techniques must be applied to these compartments also.
I. Epidemiology For Stroke Facilities Planning
Authors: Stallones Reuel A. , Dyken Mark L. , Fang Harry C. H. , Heyman Albert , Seltser Raymond , Stamler Jeremiah
Published: June 2011

The Major factors known to be associated with stroke include increasing age, hypertension, cardiovascular disease and diabetes. However, many additional data are required to substantiate the role of other risk factors.

The incidence, prevalence and mortality figures in this paper are presented in a form to be useful for palnning health facilities and manpower resources required in the proper management of stroke problems.
Continued Patency of Canine Lingual-Basilar System
Authors: Reichman O. Howard
Published: June 2011

A canine lingual-basilar system has been helpful to study the use of extracranial vessels for perfusion of the cerebral circulation. This experimental system was patent in all nine long-term animals and enlarged with time.

The principles derived from this experimental investigation have been applied to six patients in whom the superficial temporal artery was used to enhance cerebral perfusion by anastomosis to a cortical branch of the middle cerebral artery. The first four patients have had follow-up arteriography which demonstrates patency of all five new vascular channels.
The Sympathetic Nervous System and the Regulation of Cerebral Blood Flow in Man
Authors: SKINHØJ Erik
Published: June 2011

Pharmacological blockade of the α adrenergic system by 20 mg phentolemine I.V. was shown not to influence CBF in 14 patients with an intact cerebral autoregulation. If the autoregulation--tested with angiotensin--was impaired for some reason, CBF was found to follow proportionally the blood pressure changes provoked by the blockade. The physiological sympathetic stimulation provoked by distention of the bladder did not alter the CBF (seven patients). The CO
2
reactivity was unaffected by the sympathetic α blockade (six patients).

It appears from these studies that the sympathetic system does not play any substantial role in regulation of CBF in man, and thus it would seem useless to try to influence the cerebral circulation for therapeutic purposes by systemic application of drugs, which directly or indirectly work via the sympathetic system.
The Use of Medical Facilities for Cerebrovascular Disease Patients in a Country of Western Pennsylvania
Authors: CARPENTER ROBERT R. , ROGERS KENNENTH D. , REED DAVID E.
Published: June 2011

A survey of hospital, nursing home, and death certificate records, and interviews with local physicians were undertaken in a country of 201,000 population. Data from these sources indicate that the incidence of cerebrovascular disease episodes requiring medical care is somewhat higher (particularly among the aged) than the incidence of cerebrovascular disease reported in the United States population. Each year, 385 patients per 100,000 population sought medical care for cerebrovascular disease; 37% of these patients died. One county resident in eight could expect to require care for cerebrovascular disease in the decade after his retirement. To care for the affected patients, one in 20 of the county's hospital beds and one in three of its nursing home beds were required. Including only the most easily identified direct costs, the care of patients with stroke in 1971 required $2,100 per patient and a yearly expenditure of $688,000 per 100,000 population.