Large Cerebral Vessels Research Articles

Risk Reduction Strategies in Ischaemic Stroke

Stroke is a common and serious disorder, and is a leading cause of disability and death in adults. Transient ischaemic attacks are now recognised as being common precursors of stroke, with a high risk of subsequent vascular events. The majority of strokes are ischaemic in origin, and are typically due to athero-thrombosis/microatheromatosis involving a large or small cerebral blood vessel or to an embolic event. Owing to the diffuse nature of atherothrombosis, these patients are at risk of ischaemic events in other vascular beds. Options for treating patients with acute ischaemic stroke are very limited; therefore prevention is a key strategy for reducing the risk of recurrent stroke and other vascular events. Treatment of risk factors such as hypertension, diabetes mellitus, smoking and obesity is an important approach for stroke prevention. Platelets are involved in the development of thrombi and emboli, making antiplatelet therapy an important preventive strategy. Antiplatelet agents are effective in preventing recurrent ischaemic stroke and other vascular ischaemic events, such as myocardial infarction and vascular death. In some cases, anticoagulants may be effective in preventing ischaemic stroke recurrence. Carotid endarterectomy can reduce stroke risk in patients with moderate- or high-grade carotid artery stenosis. Choosing the most appropriate therapy for the individual patient is key to optimising stroke prevention.

Les manifestations neurologiques de la maladie de Behçet : analyse d’une série de 27 patients

Purpose. – To describe epidemiological and clinical characteristics of neurological involvement in Behçet’s disease (BD) and to determine a subgroup of patients at high risk for this complication. Patients and methods. – The medical notes of 105 patients with BD fulfilling the criteria of the international Study Group for Behçet’s disease were retrospectively reviewed. Patients were divided into two groups according to the presence (group 1) or not (group 2) of neurological and/or psychiatric involvement attributable to BD. The epidemiological, clinical and genetic (HLA B51 and MICA 6 frequency) features in the two groups were analysed and compared using the Kruskall-Wallis and the chi-square tests. Results. – Twenty-seven patients (25.7%) had clinical evidence of neurological involvement. They were 20 men and 7 women. The mean age at neurological onset was 34.26 ± 8.79 years. Nineteen patients (70.3%) had meningoparenchymal “MP” central nervous system involvement (brainstem: 9, hemispheric involvement: 6, spinal cord: 4, psychiatric involvement: 2, isolated pyramidal signs: 1, aseptic meningitis:1). Seven patients (25.9%) had cerebral large vessels involvement that is cerebral angio-Behçet “CAB” (intracranial hypertension: 5 cases due to cerebral venous thrombosis: 3 and pseudotumor cerebri: 2, cerebral haemorrhage: 1, cerebral arterial thrombosis: 1). One patient (3.7%) had both “MP” and “CAB” involvement. Headache was significantly more frequent in non-parenchymal patients. In group 1, complete recovery or improvement with mild neurological impairment was seen in 13 cases, improvement with severe disability in 3 cases, worsening in 1case, the course was stationary in 1 case and 3 patients died (11.2%). Arterial aneurysms were significantly more frequent in “CAB” subgroups than in subgroup 2. Conclusion. – Frequency of neurological involvements in BD was high in our study. Arterial aneurysms seem to be a risk factor to these complications. Cerebral angio-Behçet appears to be a protector factor against uveitis.

Early Detection of Cerebral Arterial Occlusion on Magnetic Resonance Angiography: Predictive Value of the Baseline NIHSS Score and Impact on Neurological Outcome

The presence of a thrombus on initial arteriography is directly related to the baseline NIHSS score. Magnetic resonance angiography (MRA) offers a noninvasive and rapid assessment of large cerebral vessel patency. We aimed at evaluating (1) the baseline NIHSS score as a tool for predicting the likelihood of an occluded artery on MRA and (2) the course of stroke within the first week according to the presence of a cerebral arterial occlusion. Patients were enrolled in this prospective study according to the following criteria: (1) acute cerebral ischemia with a neurological deficit lasting >1 h, and (2) brain MRI performed within 24 h of stroke onset. The NIHSS score assessment was performed on admission and at day 1 and day 7. The MRI protocol included: (1) T2-weighted Turbo spin echo, (2) echo-planar imaging isotropic diffusion, (3) T2*-gradient echo sequence, and (4) time of flight MRA (3D TOF Turbo MRA). The presence of a symptomatic cerebral arterial occlusion on MRA was systematically screened. Fifty-four patients were studied. Median age was 60 years. Mean time from stroke onset to NIHSS assessment was 170 ± 95 min. The mean baseline NIHSS score was 13.5 ± 7.3. The mean time from stroke onset to MRI was 384 ± 171 min. MRA was readable in 50 cases. An arterial occlusion was detected in 23 patients (46%). The median baseline NIHSS score was significantly higher in the group of patients with occlusion than in the group of patients without occlusion (18 vs. 7, p = 0.01). The predictive probability to demonstrate an arterial occlusion was related to the baseline NIHSS score. None of the patients with an NIHSS score of 1–6 (11 patients) had visible occlusion, whereas 9 (43%) out of 21 patients with an NIHSS score of 7–15 and 14 (78% ) out of 18 patients with an NIHSS score above 16 had an arterial occlusion. For an increase by one point in the NIHSS score, the odds ratio for the presence of occlusion was 1.28 (95% CI: 1.11–1.46). The course of the stroke as assessed by follow-up NIHSS score was significantly more severe if an occlusion was detected. Median day 0, day 1 and day 7 NIHSS score were, respectively, 18, 16 and 13 in patients who had an occlusion versus 7, 4 and 0 in patients who had no visible occlusion (p < 0.01). A direct relation between the baseline NIHSS score and the likelihood of the presence of an occlusion on initial MRA is demonstrated. The presence of a cerebral arterial occlusion on MRA is significantly linked to a poor neurological outcome.

The protean manifestations of varicella-zoster virus vasculopathy.

Varicella-zoster virus (VZV) vasculopathy in the central nervous system (CNS) affects large and small cerebral vessels. Large-vessel disease is most common in immunocompetent individuals, whereas small-vessel disease usually develops in immunocompromised patients. In some patients, both large and small vessels are involved. Neurological features are protean. Neurological disease often occurs months after zoster and sometimes without any history of zoster rash. Magnetic resonance imaging (MRI) scanning, cerebral angiography, and examination of cerebrospinal fluid (CSF) with virological analysis are needed to confirm the diagnosis. VZV vasculopathy patients do not always have VZV DNA in CSF, but diagnosis can be confirmed by finding anti-VZV antibody in CSF, along with reduced serum/CSF ratios of VZV immunoglobulin G (IgG) compared to albumin or total IgG. When VZV vasculopathy develops months after zoster, antiviral treatment is often effective.

Detection of Lipoprotein(a) in Intraparenchymal Cerebral Vessels: Correlation with Vascular Pathology and Clinical History

Serum levels of lipoprotein(a), Lp(a), have been shown to be associated with increased risk of atherosclerosis (AS) and AS-related diseases such as myocardial and ischemic cerebral infarcts (ICI). Lp(a) has been detected in the vascular wall of the aorta and coronary vessels, and we documented the presence of apo(a) in cerebral vessels of the Circle of Willis, associated with AS changes. In this study we further investigated and characterized the biochemical nature of Lp(a) detected in both large and small cerebral parenchymal vessels. Autopsy specimens of cerebral vessels of 51 patients were examined by immunohistochemistry with monoclonal antibodies against apo(a), apoB, and plasminogen. Lp(a) was detected in cerebral capillaries and arterioles. All of the 8 patients with ICI expressed Lp(a) in parenchymal vessels, generally (6/8) in both capillaries and arterioles. Of 43 patients without ICI only 25 had Lp(a) detected. Among the patients without ICI, there was a slightly increased incidence of parenchymal Lp(a) in those patients who had severe hypoxic brain damage (12/20) compared to those patients without severe hypoxic damage (9/23). Thus, the presence of Lp(a) in small cerebral parenchymal vessels may reflect the role of Lp(a) in ICI.

Homocysteine in Cerebrovascular Disease: an Independent Risk Factor for Subcortical Vascular Encephalopathy

Hyperhomocysteinemia is a risk factor for obstructive large-vessel disease. Here, we studied plasma concentrations of homocysteine and vitamins in patients suffering from subcortical vascular encephalopathy (SVE), a cerebral small-vessel disease leading to dementia. These results were compared to the homocysteine and vitamin plasma concentrations from patients with cerebral large vessel disease and healthy control subjects. Plasma concentrations of homocysteine, vascular risk factors and vitamin status (B6, B12, folate) were determined in 82 patients with subcortical vascular encephalopathy, in 144 patients with cerebral large-vessel disease and in 102 control subjects. Patients with SVE, but not those with cerebral large-vessel disease, exhibited pathologically increased homocysteine concentrations in comparison with control subjects without cerebrovascular disease. Patients with SVE also showed lower vitamin B6 values in comparison to subjects without cerebrovascular disease. Logistic regression analysis showed that homocysteine is associated with the highest risk for SVE (odds ratio 5.7; CI 2.5-12.9) in comparison to other vascular risk factors such as hypertension, age and smoking. These observations indicate that hyperhomocysteinemia is a strong independent risk factor for SVE.

The Functional Status of the Cardiovascular System in Children Survivors of Oncological Disease

According to data of Russian Research Institute of Children Oncology and Hematology, the incidence of oncological disease in children is rather high (220 - 240 new cases in Moscow every year). Nevertheless, when started in due time, an adequate treatment results in complete recovery with favorable longterm prognosis in up to 80% of all cases of lymphoblastic leukemia, 95% of lymphogranulomatosis, 65% of lymphosarcoma, 90% of nephroblastoma, and 100% of retinoblastoma. Most children continue to attend general school after recovery. So, examination of functional status of various physiological systems in children survivors of oncological disease is a topical problem. In treating children with oncological disease, it should be taken into account that their growing and developing physiological systems are highly sensitive to various endogenous and exogenous influences [1‐3]. The most important components of complex oncological disease treatment are radiation and chemotherapy. However, their use can be accompanied by unfavorable long-term side-effects associated with lesions in unaffected tissues and organs (dysfunctions in urogenital, endocrine, cardiorespiratory, and/or locomotor systems). It has been shown [4] that 15-year survivors of oncological disease diagnosed during their childhood and treated chemotherapeutically have increased cardiac mortality rates. In this connection, this work was designed to study the functional status of the cardiovascular system in 7- to 17-year-old children and adolescents with long-lasting remissions after cured malignant diseases. All the children examined were in-patients in the rehabilitation department of Research Institute of Children Oncology and Hematology; they continue their schooling according to the standard curricula. Central hemodynamics was examined with echocardiography (EchoCG) and electrocardiography (ECG). The readings were taken with patients resting in the recumbent position. The following EchoCG parameters were recorded: the systolic and diastolic myocardium thickness in the left ventricular posterior wall; enddiastolic and end-systolic left ventricular size and volume; stroke volume; cardiac output; ejection fraction; systolic shortening fraction; systolic speed of the circulatory myocardial fiber shortening; and the blood ejection time. The ECG was recorded with 12 common leads; it was checked for the presence of various disturbances of cardiac rhythm, intraventricular conductance, myocardial recovery, electrical alternation, or decrease in ECG-wave voltage. The volumetric and tonic parameters of cerebral and antebrachial circulation were determined with focused and tetrapolar impedance plethysmography. The study was performed with 75 patients with histories of various malignant diseases (blood malignancies accounted for approximately 70% of cases examined). According to EchoCG data, about 50% of children examined had various myocardial disorders. Frequently (in 50% of cases) there was a 12‐35% decrease in pumping and contractile myocardium capacity. A 12‐20% thinning of the left ventricular posterior wall (relative to the age-specific norm) was found in 20% of children, and was frequently accompanied by the transition zone shift towards the left thoracic leads. Fifteen percent of patients had a 10‐20% widening of the left ventricle expressed on ECG as an abnormal amplitude ratio of R-wave in left V leads. These disorders were combined in 20% of the children. Cardiac arrhythmia, bradycardia, tachycardia, impairments of intraventricular conductance or myocardial recovery, electrical alternation or decrease in ECG-wave voltage were observed in 20, 22, 14, 75, 26, 18, and 10% of the children, respectively. Changes of this complexity in morphofunctional parameters may be regarded as a manifestation of myocardiac dystrophy. Up to 80% of children examined had impairments of peripheral circulation such as the tonic instability of large cerebral and antebrachial vessels or a significant decrease in the tone of small and medium-size antebrachial vessels; in 50% of cases there were restrictions of venous backflow caused by decreased venous tone. These data are characteristic of the high incidence of vascular dystonias in this group of children.

P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature; contribution of P2X and P2Y receptors.

Purine and pyrimidine nucleotides evoke changes in the vascular tone of medium to large cerebral vessels through the activation of P2 purinoceptors. We have applied P2 receptor drugs to rat pial arterioles and measured changes in arteriole diameter (o.d. 40-84 micrometer at rest), and recorded currents from arteriolar smooth muscle cells using patch-clamp techniques. Transient vasoconstrictions and rapidly inactivating currents were evoked by alpha,beta-methylene ATP (0.1-30 micrometer) and were sensitive to the P2 receptor antagonists suramin and iso-PPADS. UTP and UDP (0.1-1000 micrometer) evoked sustained suramin-sensitive vasoconstrictions. ATP (0.1-1000 micrometer) and 2-methylthioATP (2MeSATP, 300 micrometer) evoked transient vasoconstrictions followed by sustained vasodilatations. ADP application resulted in only vasodilatation (EC50 approximately 4 micrometer). Vasodilator responses to ATP, 2MeSATP or ADP were unaffected by suramin (100 micrometer). RT-PCR analysis indicated that P2X1-7 and P2Y1,2,6 RNA can be amplified from the pial sheet. Our results provide direct evidence for the presence of functional P2X receptors with a phenotype resembling the P2X1 receptor subtype on cerebral resistance arterioles. The pharmacological properties of the pyrimidine-evoked responses suggest that a combination of P2Y2- and P2Y6-like receptors are responsible for the sustained vasoconstrictions. It is therefore likely that the nucleotides and their associated receptors are involved in a complicated regulatory system to control cerebral blood pressure.

Stroke in Children.

Identification and treatment of the underlying risk factors for stroke reduce the potential for additional strokes; therefore, a thorough search for treatable risk factors is justified. Because some risk factors can have a cumulative effect, even children with known risk factors for stroke sometimes need to be evaluated for other conditions. Cerebral angiography is often helpful; I recommend angiography in any child with an unexplained infarction or hemorrhage. Angiography is especially important in children with intraparenchymal hemorrhage because more than one third of such children will prove to have some type of potentially treatable congenital vascular anomaly such as an arteriovenous malformation (AVM) or aneurysm. The evidence that periodic blood transfusion effectively prevents cerebral infarction due to sickle cell disease is compelling. Transfusions apparently must be continued indefinitely to maintain the reduction of stroke risk, and without iron chelation, chronic transfusion eventually results in severe iron toxicity and, most likely, death, so the decision to begin transfusion is not an easy one. Measurement of the time-averaged mean flow velocity in the large cerebral vessels with transcranial Doppler (TCD) is highly predictive of stroke risk in these children, enough to justify its routine use in screening patients with sickle cell disease for stroke risk. I believe that patients with sickle cell disease should be offered chronic transfusion after an initial large-vessel stroke or when the TCD results suggest a high risk of stroke. The family must be made aware of the serious complications of chronic transfusion and the importance of complying with chelation once it is started. There are no controlled clinical trials to guide the use of anticoagulants, antiplatelet agents, or thrombolytic agents in children, although these drugs are being used more and more often in pediatric patients. For the most part, our approach has been adapted from our experience with adults. Heparin followed by warfarin is often used for sinovenous thrombosis and for arterial dissection. I also suggest long-term anticoagulation for children with coagulopathy or a high risk of embolism due to congenital or acquired cardiac disease. It is reasonable to use a thrombolytic agent in children with an acute infarction; because few children present soon enough after the onset of symptoms, however, thrombolysis is infrequently used. Aspirin is used more than other antiplatelet agents in children, largely because of years of experience with aspirin and the lack of evidence that other agents are more effective. Despite its frequent use, there are no unequivocal indications for the use of aspirin in children. Aspirin is often started empirically in children suspected to be at substantial risk for additional ischemic stroke but whose risk is ill defined, an approach not too dissimilar from that often used in adult patients. Although the risk of Reye's syndrome in a child taking daily aspirin for stroke prevention is a common concern, I know of no published examples of children who developed Reye's syndrome while taking prophylactic aspirin. This apparently low risk must be weighed against the often-considerable risk of ischemic stroke that could be reduced by the use of daily aspirin. In situations such as vasculopathy or infarction of unknown cause, the small risk of Reye's syndrome seems acceptable.

Naturally occurring and experimentally induced beta-amyloid deposits in the brains of marmosets (Callithrix jacchus).

Cerebral beta-amyloid occurs in elderly animals of some species and in Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally with brain tissue from a patient with Alzheimer's disease. Six years later, when the monkeys were middle aged, we found moderate numbers of intracerebral plaques and cerebrovascular deposits containing beta-amyloid. We have re-examined these brains and those of 10 other marmosets injected with brain homogenate containing beta-amyloid, and have found some beta-amyloid in animals injected more than 4 years previously. We have found beta-amyloid in 4 of 26 elderly control marmosets, but not in 9 young to middle-aged control marmosets. The beta-amyloid found in middle aged marmosets injected with Alzheimer brain tissue was, therefore, not a consequence of their age. Deposits in large cerebral vessels in elderly marmosets, and in marmosets previously injected with brain tissue containing beta-amyloid, reacted with antibodies to Abeta and Abeta1-40; plaques and microvessel deposits reacted with antibodies to Abeta and Abeta1-42.

In Vivo Animal Models of Cerebral Vasospasm: A Review

BACKGROUND: Cerebral vasospasm is delayed-onset cerebral arterial narrowing in response to blood clots left in the subarachnoid space after spontaneous aneurysmal subarachnoid hemorrhage (SAH). Ideally, studies on the pathogenesis and treatment of cerebral vasospasm in humans should be conducted using human cerebral arteries. Because in vivo experiments using human vessels are not possible, and postmortem pathological examination of human arteries in vasospasm provides only a limited amount of information, a number of animal models of vasospasm have been developed. METHODS: The literature was searched to find all references to in vivo animal models of SAH and vasospasm. An online search of the medical database MEDLINE was initially performed using the key words “cerebral,” “vasospasm,” “subarachnoid,” “hemorrhage,” “animal,” and “model.” References were checked to determine the first description of each in vivo animal model. RESULTS: Fifty-seven models of SAH and vasospasm were identified. These models used one of three techniques to simulate SAH: 1) an artery was punctured allowing blood to escape and collect around the artery and its neighbors; 2) an artery was surgically exposed, and autologous blood obtained from another site was placed around the artery; or 3) blood from another site was injected into the subarachnoid space and was allowed to collect around arteries. Each technique has advantages and disadvantages. The majority of animal models of SAH and vasospasm use intracranial arteries; however, extracranial arteries have also been used recently in vasospasm experiments. These studies seem easier and less costly to perform, but concerns exist regarding the physiological dissimilarity between systemic and cerebral arteries. CONCLUSION: The model of SAH and vasospasm used most frequently is the canine “two-hemorrhage” model, in which two injections of blood into the dog’s basal cistern performed 48 hours apart result in greater arterial vasoconstriction than that effected by a single injection of blood. On the basis of its ability to accurately predict what occurs in human SAH, the best model of vasospasm seems to be the primate model in which a blood clot is surgically placed around the large cerebral vessels at the base of the monkey’s brain.

Constrictor responses of the rat basilar artery during diabetes mellitus

Diabetes mellitus produces abnormalities of the endothelium and impairs endothelium-dependent dilatation of large and small cerebral blood vessels. However, the effect of diabetes mellitus on cerebral vasoconstriction and the modulatory influence of nitric oxide on cerebral vasoconstriction is unclear. Thus, the first goal of this study was to examine the effect of diabetes mellitus on constrictor responses of the basilar artery in vivo. Our second goal was to examine a potential role for nitric oxide in modulating constrictor responses of the basilar artery. A craniotomy was performed over the ventral medulla to expose the basilar artery. The diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (3–4 months after injection of streptozotocin; 50–60 mg/kg i.p.) rats in response to angiotensin II, arginine vasopressin, endothelin-1, and the thromboxane analogue, U-46619. Topical application of angiotensin II (10 and 100 nM) produced only minimal changes in diameter of the basilar artery which were similar in nondiabetic and diabetic rats ( p>0.05). Arginine vasopressin (0.1 and 1.0 nM), endothelin-1 (10 and 50 nM), and U-46619 (10 and 100 nM) produced marked dose-related constriction of the basilar artery which also was similar in nondiabetic and diabetic rats ( p>0.05). Next, we examine whether the synthesis/release of nitric oxide played a role in constriction of the basilar artery in response to the agonists. We found that l-NMMA (1.0 μM) did not alter constrictor responses of the basilar artery in nondiabetic and diabetic rats. Thus, responses of the basilar artery to important vasoactive agonists are not altered by diabetes mellitus. In addition, it does not appear that the synthesis/release of nitric oxide modulates constrictor responses of the basilar artery to angiotensin II, arginine vasopressin, endothelin-1 and U-46619. We suggest that preservation of vasoconstrictor responses, coupled with impaired vasodilator responses, may contribute to the pathogenesis of cerebrovascular abnormalities associated with diabetes mellitus.

Retrograde cerebral perfusion provides limited distribution of blood to the brain: A study in pigs

Objective: The objective of this study was to investigate flow distribution during retrograde and antegrade cerebral perfusion with India ink as a marker. Methods: Ten pigs received cerebral perfusion with a solution containing 50% filtered India ink for 5 minutes either antegradely through both internal carotid arteries at a flow of 180 to 200 ml/min ( n = 5) or retrogradely via the superior vena cava at a flow of 300 to 500 ml/min ( n = 5). The brains were then fixed for quantitative measurement of the density of ink-filled capillaries (reported as a percentage of the total selected area). The assessment was done with the use of an in-house software program. Results: In the antegrade cerebral perfusion group, the intracranial arterial and venous systems were completely filled with ink. The gray matter was colored uniformly black, and light coloring was observed in the white matter. During retrograde cerebral perfusion, the majority of ink was returned to the inferior vena cava, and only a small amount of ink was found in the innominate artery draining from the brain. Massive ink filling was observed in the sagittal sinus and other venous sinuses in all the pigs. Vessels on the surface of the brain and large vessels in the brain were also well filled with ink. However, only 10% of capillaries were filled with ink during retrograde cerebral perfusion relative to the number observed with antegrade cerebral perfusion. Conclusions: Retrograde cerebral perfusion supplies a limited amount of blood to brain tissue, which flows mainly through superficial and large deep cerebral vessels. (J Thorac Cardiovasc Surg 1997;114:660-5)

Effects of serotonin on cerebral circulation after middle cerebral artery occlusion.

Serotonin (5-HT) produces constriction of peripheral collateral blood vessels. Using an animal model, the authors tested the hypothesis that 5-HT constricts collateral vessels in the cerebrum. A branch of the middle cerebral artery (MCA) was occluded proximally and cannulated distally in anesthetized dogs. Blood flow to the area at risk for infarction was detected by perfusing the cannulated MCA branch with microsphere-free blood during systemic injection of radioactive microspheres (shadow flow technique). Blood flow to collateral-dependent and normal cerebrum was measured during intravenous infusion of 5-HT (10 and 40 mg/kg/minute). Serotonin produced a dose-related reduction of blood flow to collateral-dependent cerebrum, increased collateral vessel resistance in large cerebral arteries and collateral vessels, and decreased cerebral artery perfusion pressure. In contrast, blood flow to normal cerebrum was not altered because a decrease in small vessel resistance effectively compensated for a decrease in MCA perfusion pressure. These findings indicate that 5-HT produces constriction of collateral vessels in the cerebrum. This response is clearly different from normal small cerebral vessels, which dilate during 5-HT infusion.

Cardiovascular risk factors and hyalinization of renal arterioles at autopsy. The Honolulu Heart Program.

Nephrosclerosis, commonly found in subjects with hypertension and diabetes, is marked by hyalinization of arterioles and fibroplasia of small arteries in the renal cortex. Cardiovascular risk factors that predicted subsequent hyalinization of renal arterioles at autopsy were identified, using data from the Honolulu Heart Program, a prospective epidemiological study of cardiovascular disease (CVD) in Japanese-American men. Among 8006 participants at baseline, 1381 died between 1965 and 1982; 285 of these had a protocol autopsy, and 150 had assessments of arteriolar hyalinization from renal tissue. Subjects were categorized into four groups on the basis of the number of hyalinized arterioles per square centimeter of renal tissue, and CVD risk factor levels and proportions were compared across these groups with the use of general linear models and logistic regression. Multivariate assessment using logistic regression demonstrated that diastolic blood pressure (DBP) and glucose level were positively associated and alcohol intake was negatively associated with an elevated degree of renal arteriolar hyalinization, independent of other CVD risk factors. The odds ratios for elevated hyalinization associated with a 10-mm Hg increase in DBP, a 20-mg/dL increase in glucose level, and a 30-mL/d increase in alcohol intake were 1.97 (95% confidence interval [CI] = 1.24-3.12), 1.23 (95% CI = 1.07-1.41), and 0.24 (95% CI = 0.11-0.55), respectively. Associations were similar when prevalent cases of CVD were excluded and when autopsy selection bias was taken into account. Renal arteriolar hyalinization was also more strongly associated with atherosclerosis in the larger cerebral vessels (Spearman's r = .59, P < .001) than in the coronary arteries (r = .16, P = .073) and aorta (r = .24, P = .022). Hyalinization was significantly related to cardiovascular-renal mortality, and this association was accounted for by other CVD risk factors. These findings suggest that blood pressure, glucose level, and alcohol intake are independent predictors of hyalinization in renal arterioles and that this type of renal vasculopathy may be a marker for atherosclerosis in other vascular regions, particularly the cerebral vessels. The protective association involving alcohol and the possibility that renal arteriolar hyalinization may be an indicator of cerebral atherosclerosis may warrant investigation in other populations.

A method for isolating and culturing vascular smooth muscle cells from porcine cerebral arteries

Cerebral blood vessels have unique properties when compared to most peripheral vascular beds. One such property is that large cerebral vessels are involved in the regulation of cerebral vascular resistance. Studying smooth muscle cells isolated from these vessels will determine how phenotypic properties of these cells contribute to unique cerebrovascular function. Therefore we developed a method of culturing smooth muscle cells from explants of cerebral arteries of porcine brains obtained, gratis, from a local slaughter house. Cells isolated and cultured by the methods described herein were of smooth muscle origin as indicated by histochemical staining for smooth muscle α-actin. Further, we examined the response of the cultured cells to agonists which activate the cGMP dependent vasodilator system by stimulating soluble guanylyl cyclase (nitroglycerin and sodium nitroprusside) or particulate guanylyl cyclase (C-type natriuretic peptide). Also, forskolin activation of adenylyl cyclase was examined. These agents stimulated an increase in intracellular cGMP and cAMP in a manner that was reproducible in every cell isolation (20 brains) and which remained unchanged through nine passages. Additionally, the cells could be frozen, thawed and replated without loss of responsiveness to these agents. The protocol reported here provides a method for culturing cerebral artery smooth muscle cells that is inexpensive, relatively simple, and which yields cells that can be utilized through multiple passages.

Magnetic resonance angiography in moyamoya disease.

Spontaneous occlusion of the circle of Willis, i.e., moyamoya disease (MMD), is a clinical disease entity angiographically characterized by progressive and bilateral stenosis of the carotid bifurcation, with a hazy collateral network at the base or convexity of the brain. Although the importance of computed tomography (CT) and conventional magnetic resonance (MR) imaging in diagnosing MMD has already been determined, conventional arteriography is still regarded as necessary for definitive diagnosis. Magnetic resonance angiography (MR-A) is a very recent vascular imaging technique which allows noninvasive and direct imaging of vessels without the use of contrast medium. We present four pediatric cases of MMD, evaluated by conventional angiography, CT, MR imaging, and MR-A. Our data demonstrate that MR-A is successful both in allowing detection of occlusive disease of the basal portion of the internal carotid artery and large branch basal cerebral vessels and demonstrating the collateral vessels at the base of the brain. As a noninvasive procedure, MR-A promises to become a valuable alternative to classical angiography in the diagnosis of MMD.

Alpha 2-adrenergic agonist effects on normocapnic and hypercapnic cerebral blood flow in the dog are anesthetic dependent.

alpha 2-Adrenergic receptors are found on large and small cerebral vessels, but their role in control of cerebral blood flow (CBF) and cerebral vascular reactivity is unclear. We assessed the effects of dexmedetomidine (DEX), a highly selective alpha 2-adrenergic agonist, on the cerebrovascular response to hypercapnia in dogs anesthetized with either pentobarbital (PENTO) or isoflurane (ISO), drugs which produce different levels of CBF at a similar level of cerebral oxygen consumption (CMRO2). Dogs were anesthetized with either PENTO, 30 mg/kg, n = 6, or ISO 1.4% end-tidal, n = 7. CBF (radiolabeled microspheres) was determined during normocapnia and hypercapnia at baseline (pre-DEX), after DEX (10 micrograms/kg, intravenous bolus, plus an additional 5 micrograms/kg during hypercapnia), and after administration of a selective alpha 2-adrenergic receptor antagonist (atipamezole, 500 micrograms/kg, intravenous bolus). In the PENTO group, CBF increased from 31 +/- 3 to 137 +/- 24 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg) at pre-DEX and there was no change in normocapnic CBF or hypercapnic blood flow after DEX or atipamezole. In the ISO group, at pre-DEX, CBF increased from 86 +/- 8 to 166 +/- 19 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

α2-ADRENERGIC AGONIST EFFECTS ON NORMOCAPNIC AND HYPERCAPNIC CEREBRAL BLOOD FLOW IN THE DOG ARE ANESTHETIC-DEPENDENT

alpha 2-Adrenergic receptors are found on large and small cerebral vessels, but their role in control of cerebral blood flow (CBF) and cerebral vascular reactivity is unclear. We assessed the effects of dexmedetomidine (DEX), a highly selective alpha 2-adrenergic agonist, on the cerebrovascular response to hypercapnia in dogs anesthetized with either pentobarbital (PENTO) or isoflurane (ISO), drugs which produce different levels of CBF at a similar level of cerebral oxygen consumption (CMRO2). Dogs were anesthetized with either PENTO, 30 mg/kg, n = 6, or ISO 1.4% end-tidal, n = 7. CBF (radiolabeled microspheres) was determined during normocapnia and hypercapnia at baseline (pre-DEX), after DEX (10 micrograms/kg, intravenous bolus, plus an additional 5 micrograms/kg during hypercapnia), and after administration of a selective alpha 2-adrenergic receptor antagonist (atipamezole, 500 micrograms/kg, intravenous bolus). In the PENTO group, CBF increased from 31 +/- 3 to 137 +/- 24 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg) at pre-DEX and there was no change in normocapnic CBF or hypercapnic blood flow after DEX or atipamezole. In the ISO group, at pre-DEX, CBF increased from 86 +/- 8 to 166 +/- 19 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of cerebrovascular reactivity in patients with unilateral asymptomatic carotid artery stenosis.

Intracranial hemodynamic status varies in patients with unilateral significant carotid artery stenosis. It ranges from normal, because of sufficient collaterals, to poor, because of a severely reduced blood supply that puts the patient at an increased risk of stroke or cerebral ischemia. The present study examined patterns of abnormal cerebrovascular hemodynamics in patients with asymptomatic carotid artery stenosis. The CO2 reactivity of the cerebral resistance index (CRi) and of mean blood flow velocity (vmean) was determined via transcranial Doppler sonography in 91 patients with unilateral high-grade to threadlike carotid artery stenosis and in 37 control subjects. The interhemispheric asymmetry of CRi reactivity of the control group was used to differentiate between normal and abnormal findings. We found that 64.8% of the patients demonstrated normal CRi asymmetry with comparable CRi reactivity (ipsilateral, 4.42 +/- 0.44 %CRi/vol%CO2; contralateral, 4.51 +/- 0.39 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.080 +/- 0.004 m/s per vol%CO2; contralateral, 0.079 +/- 0.005 m/s per vol%CO2) at both hemispheres. In 16.5% of the patients, CRi reactivity was supranormal at the affected hemisphere. This phenomenon was due to an exaggerated dilatory response of the ipsilateral hemisphere and was combined with an absent CRi reactivity of the contralateral hemisphere (ipsilateral, 6.63 +/- 1.03 %CRi/vol%CO2; contralateral, -1.16 +/- 1.78 %CRi/vol%CO2). In contrast, hemispheric vmean reactivities were comparable (ipsilateral, 0.078 +/- 0.008 m/s per vol%CO2; contralateral, 0.077 +/- 0.008 m/s per vol%CO2). The remaining 18.7% showed severely diminished ipsilateral CRi reactivity (ipsilateral, 1.91 +/- 0.83 %CRi/vol%CO2; contralateral, 8.48 +/- 1.00 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.073 +/- 0.007 m/s per vol%CO2; contralateral, 0.108 +/- 0.012 m/s per vol%CO2; P < .01), compatible with a significantly reduced perfusion pressure at the poststenotic hemisphere. Most asymptomatic patients do not suffer from severely abnormal hemodynamics at the poststenotic hemisphere. One small subgroup of patients presented with severely disturbed ipsilateral hemodynamics; another small subgroup demonstrated a steal phenomenon with secondary dilation of large cerebral vessels at the contralateral hemisphere. These subgroups require specific evaluation of proper treatment.