Abstract P066: Purinergic Receptor Function In The Middle Cerebral Artery From Clopidogrel-treated Rabbits

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Dawn Kuszynski ◽  
Barbara Christian ◽  
Anne M Dorrance ◽  
Dale A Lauver

Arterial thrombosis is the leading cause of death in the developed world and hypertensive patients are at an increased risk. Dual antiplatelet therapy, consisting of low-dose aspirin in combination with a P2Y 12 antagonist, is the most common preventative treatment for arterial thrombosis. Clopidogrel, a P2Y 12 antagonist, is associated with cerebral microbleeds and intracerebral hemorrhages. We have previously reported in rabbits that clopidogrel (3mg/kg) induces bleeding at lower doses than required to inhibit platelet aggregation, making it unlikely that the clopidogrel-mediated bleeding events are the result of platelet inhibition. I hypothesized that clopidogrel was acting on other purinergic receptors to impair artery function due to the structural similarity of the metabolites of clopidogrel. Purinergic receptors, P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 , are expressed in the endothelium of cerebral vessels. The purpose of this study was to determine the effects of clopidogrel on vascular function in response to activation of P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 . The middle cerebral artery (MCA) was used as it is the site most common for cerebrovascular events. New Zealand white rabbits (n=3) were treated for 3 days with vehicle or clopidogrel (3mg/kg/day) prior to MCA isolation. Myogenic tone was allowed to develop before assessing the response of the MCA to increasing concentrations (10 -9 -10 -5 M) of specific purinergic receptor agonists P2Y 1 : MRS 2365; P2Y 2 : MRS 2768; P2Y 4 : MRS 4062; P2Y 6 : MRS 2693. If myogenic tone was not generated the MCA was preconstricted with 10 -6 M serotonin. Response was analyzed by two-way ANOVA and compared to vehicle using Dunnett’s post-test. In all cases, p < 0.05 denote statistical significance. Constriction was calculated as a percent change from baseline. Stimulation with the P2Y 4 agonist resulted in a mean maximal constriction of 28.95% (28.95 of 100) for vehicle and 52.72% (52.72 of 100) for 3mg/kg clopidogrel. There was no significant difference upon stimulation with the P2Y 1 , P2Y 2 , or P2Y 6 agonists compared to vehicle. These data suggest that clopidogrel has vascular effects on the P2Y 4 receptor expressed in the MCA and may explain the cerebral bleeding side effects observed.

2017 ◽  
Vol 10 (7) ◽  
pp. 620-624 ◽  
Author(s):  
Hamidreza Saber ◽  
Sandra Narayanan ◽  
Mohan Palla ◽  
Jeffrey L Saver ◽  
Raul G Nogueira ◽  
...  

BackgroundEndovascular thrombectomy has demonstrated benefit for patients with acute ischemic stroke from proximal large vessel occlusion. However, limited evidence is available from recent randomized trials on the role of thrombectomy for M2 segment occlusions of the middle cerebral artery (MCA).MethodsWe conducted a systematic review and meta-analysis to investigate clinical and radiographic outcomes, rates of hemorrhagic complications, and mortality after M2 occlusion thrombectomy using modern devices, and compared these outcomes against patients with M1 occlusions. Recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 or modified TICI 2b/3.ResultsA total of 12 studies with 1080 patients with M2 thrombectomy were included in our analysis. Functional independence (modified Rankin Scale 0–2) rate was 59% (95% CI 54% to 64%). Mortality and symptomatic intracranial hemorrhage rates were 16% (95% CI 11% to 23%) and 10% (95% CI 6% to 16%), respectively. Recanalization rates were 81% (95% CI 79% to 84%), and were equally comparable for stent-retriever versus aspiration (OR 1.05; 95% CI 0.91 to 1.21). Successful M2 recanalization was associated with greater rates of favorable outcome (OR 4.22; 95% CI 1.96 to 9.1) compared with poor M2 recanalization (TICI 0–2a). There was no significant difference in recanalization rates for M2 versus M1 thrombectomy (OR 1.05; 95% CI 0.77 to 1.42).ConclusionsThis meta-analysis suggests that mechanical thrombectomy for M2 occlusions that can be safely accessed is associated with high functional independence and recanalization rates, but may be associated with an increased risk of hemorrhage.


2012 ◽  
Vol 2 (2) ◽  
pp. 77-80
Author(s):  
Md Abu Taher ◽  
Nuzhat Tasmin ◽  
AS Mohiuddin ◽  
Md Mohit Ul Alam ◽  
Md Mofazzal Sharif ◽  
...  

This observational type of descriptive study was carried out in the Department of Radiology and Imaging, BIRDEM selecting 70 Bangladeshi pregnant babies with the aim to find out the normogram of foetal middle cerebral artery Doppler flow velocity indices and correlation between Doppler flow velocity indices [Resistance Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D) & Peak Systolic Velocity (PSV)] of foetal middle cerebral artery and gestational age in normal pregnancies of 20 to 40 weeks. It was observed that RI, PI and S/D were decreased with the advance of gestational age but PSV was increases with the advance of gestational age. Statistical analyses showed there were significant difference between mean PSV, RI and PI before and after 25 weeks of gestation. No significant difference was found between mean S/D before and after 25 weeks of gestation. It was observed from Correlation analysis between Doppler indices with independent gestational age that all the Doppler indices of foetal middle cerebra artery was positively correlated with the whole gestation period. The statistical analysis showed only PSV and RI were significantly correlated with the gestational age. Simple regression analysis between dependent Doppler index with independent gestational age before and after 25 weeks revealed that all the Doppler indices had positive relationship with the corresponding gestational age but relationship between PSV and PI (before 25 weeks) with their corresponding gestational ages were only statistically significant.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12306 Birdem Med J 2012; 2(2) 77-80


2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.


2008 ◽  
Vol 65 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Radojica Stolic ◽  
Goran Trajkovic ◽  
Vladan Peric ◽  
Aleksandar Jovanovic ◽  
Dragica Stolic ◽  
...  

Backgraund/Aim. Hemodialysis catheter, as an integral part of hemodialysis, is a catheter placed into the jugular, subclavian and femoral vein. The most common catheter-related complications are infections and thrombosis. The aim of the study was to analyze the prevalence of complications associated with differently inserted central-vein catheters for hemodialysis. Methods. The study was organized as a prospective examination during the period from December 2003 to November 2006, and included all patients who needed an active depuration by hemodialysis, hospitalized at the Clinical Center Kragujevac. The subject of the study were 464 centralvein catheters inserted during the mentioned period and there were recorded all complications related to the placement and usage of catheters. Results. The largest percent of inserted catheters was into the femoral vein ? 403 (86.8%), significantly less into the jugular vein ? 42 (9.2%), while into the subclavian vein there were placed only 19 catheters (4%). The average of femoral catheter functioning was 17 catheter days, in jugular catheters it was 17.3 days while the subclavian catheters had an average rate of functioning of 25.9 catheter days; there was found a statistically significant difference regarding the duration of functioning (p = 0.03). By microbe colonization of smear culture of the skin at the catheter insertion site, in clinically present suspicion of catheter infection, there was obtained a positive finding in 5.5% of catheters placed into the femoral vein and 7.1% of catheters instilled into the jugular vein, of which Staphylococcus aureus was the most important bacterial type, without statistically significant difference (p = 0.51). Haemoculture, done when there was a suspicion of bacteriemia, was positive in 3.7% of the patients with femoral and 4.8% with jugular catheters; Staphylococcus aureus was the most common bacteria type, but there was no statistically significant difference (p = 0.65). Colonizing the smears of the cut catheter tops, there was found a positive finding in 8.9% of femoral and 4.7% of jugular catheters in which the mentioned type of staphylococcal bacteria was prevalent, without statistically significant difference (p = 0.82). In 77% of femoral, 71.4% of jugular and 68.4% of subclavian catheters, there were no complications associated with insertion and manipulation of catheters for hemodialysis and the difference was at the limits of statistical significance (p = 0.06). Conclusion. Unconvincing rate of infections and a smaller percent of serious complications associated with the placement and use of central vein catheters instilled into the femoral vein, indicate that personal experience is sufficient recommendation to convince us that femoral vein does not represent a region with an increased risk for insertion of hemodialysis catheters.


2019 ◽  
Vol 7 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Valentina Tofiloska ◽  
Maria Krstevska ◽  
Ana Daneva-Markova ◽  
Viktorija Jovanovska

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kunakorn Atchaneeyasakul ◽  
Amer M Malik ◽  
Dileep R Yavagal ◽  
Mehdi Bouslama ◽  
Diogo C Haussen ◽  
...  

Introduction: Recent trials demonstrated that mechanical thrombectomy improve functional outcome in anterior circulation acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) of the middle cerebral artery (MCA) M1 segment. However, such data regarding AIS due to MCA M2 segment ELVO is limited. Analysis of the STAR, SWIFT, and SWIFT-PRIME trials found thrombectomy in MCA M2 occlusion to be feasible in achieving successful reperfusion. The most optimal technique and/or device used for such reperfusion is not clearly defined. We aim to compare the outcome for the contemporary techniques and devices used for thrombectomy of AIS patients due to MCA M2 ELVO. Methods: A retrospective review of AIS patients with MCA M2 ELVO receiving thrombectomy from three tertiary care academic medical centers was conducted. Thrombectomy technique and thrombectomy device utilized were recorded. Outcomes were successful angiographic reperfusion (TICI ≥2b), favorable modified Rankin Scale (mRS≤2) at discharge and at 90 days, and rate of symptomatic intracerebral hemorrhage (sICH). Results: From October 1999 through June 2016, 253 AIS patients underwent thrombectomy for MCA M2 ELVO. Thrombectomy methods utilized were Stent-retriever (n=118), Aspiration only [manual or Penumbra device] (n=83), and MERCI retriever (n=52). Table 1 shows rate of outcomes measured. There was no difference in baseline NIHSS or in stroke onset to groin puncture time. Stent-retriever group showed a significantly higher recanalization rate, lower sICH rate, and favorable 90-day mRS versus Aspiration group or MERCI group, respectively. No significant difference was seen in discharge mRS between the groups. Conclusions: Thrombectomy for AIS patients with MCA M2 ELVO with Stent-retriever appears to be feasible with a significantly higher rate of recanalization, lower sICH rate, and favorable 90-day mRS when compared to Aspiration and MERCI.


2019 ◽  
Vol 90 (3) ◽  
pp. e1.2-e1
Author(s):  
S Moughal ◽  
D Boeris ◽  
A Hainsworth ◽  
E Pereira ◽  
A Shtaya ◽  
...  

ObjectivesTo compare the outcomes of decompressive craniectomy (DC) with craniotomy and debulikng of stroke tissue (Strokectomy (SC)) for malignant MCA infarction at our centre.DesignRetrospective records review.SubjectsAll Patients with malignant MCA infraction that underwent DC and SC between Jan 2012 and Sep 2017.Methods20 patients had DC (11F/9M, mean age 44.7±1.8 y) and four patients had SC (1F/3M) 51.5±5.9 7 y). Outcomes were assessed by Modified Rankin Scale (mRS) scores before surgery and at latest follow up (3–6 months). mRS was dichotomised as good (0–3) and poor (4–6). Craniotomy size was measured by antero-posterior (AP) diameter and compared between the groups.Results18 patients (90%) of the DC group had mRS 4–6 before surgery versus 100% in the SC group. Post-surgery 15 patients (75%) of the DC group had poor outcome with 7 mortalities (35%) in comparison to one patient (25%) with poor outcome in the SC group and no mortalities. The average craniotomy size in DC was 120.1±4.1 mm versus 85.5±13.1 mm in the SC, p=0.003 students t test). Six patients of the DC group underwent cranioplasty where two developed post-operative seizures. There was no significant difference in age, sex and side of craniotomy (7 Left/13 Right in DC vs 2 Left/2 Right in SC).ConclusionsStrokectomy is comparable to decompressive craniectomy in outcomes without taking the extra risks and costs of cranioplasty. Further studies are required to promote this approach.


Cephalalgia ◽  
1990 ◽  
Vol 10 (2) ◽  
pp. 87-94 ◽  
Author(s):  
Arve Dahl ◽  
David Russell ◽  
Rolf Nyberg-Hansen ◽  
Kjell Rootwelt

Transcranial Doppler and rCBF examinations were carried out in 25 cluster headache patients. Spontaneous and glyceryl trinitrate (nitroglycerin) provoked attacks were accompanied by a bilateral decrease in middle cerebral artery blood flow velocities. This decrease was more pronounced on the symptomatic side but the difference did not reach statistical significance. Mean hemispheric blood flow and rCBF were within normal limits during provoked attacks and similar to those found when patients were attack-free. During cluster periods middle cerebral artery velocities were significantly higher on the symptomatic side. Glyceryl trinitrate caused a bilateral middle cerebral artery velocity decrease which was significantly greater on the symptomatic side. Attacks provoked by glyceryl trinitrate appeared to begin when the vasodilatory effect of this substance was receding.


Neurosurgery ◽  
2002 ◽  
Vol 50 (5) ◽  
pp. 1026-1031 ◽  
Author(s):  
Jose G. Romano ◽  
Alejandro M. Forteza ◽  
Mauricio Concha ◽  
Sebastian Koch ◽  
Roberto C. Heros ◽  
...  

Abstract OBJECTIVE: To determine the frequency and characteristics of microembolic signals (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the presence of MES and vasospasm. Each middle cerebral artery was monitored for 30 minutes three times each week. Patients were excluded if they had traumatic SAH or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1–16 d) after SAH and lasted 6.6 days (1–13 d). Eleven individuals without SAH or other cerebrovascular diseases who were treated in the same unit served as control subjects. Each patient underwent monitoring of both middle cerebral arteries a mean of three times; therefore, 46 vessels were studied (a total of 138 observations). Control subjects underwent assessment of each middle cerebral artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16 of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with 2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P &lt; 0.05). MES were observed for 83% of patients with clinical vasospasm and 54% of those without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138 vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of those without vasospasm. Aneurysms proximal to the monitored artery were identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were common in SAH, occurring in 70% of cases of SAH and one-third of all vessels monitored. Although MES were more frequent among patients with clinical vasospasm, this difference did not reach statistical significance. We were unable to demonstrate a relationship between ultrasonographic vasospasm and MES, and the presence of a proximal secured or unsecured aneurysm did not alter the chance of detection of MES. Further studies are required to determine the origin and clinical relevance of MES in SAH.


2016 ◽  
Vol 124 (4) ◽  
pp. 1114-1122 ◽  
Author(s):  
Shalva Eliava ◽  
Yury Pilipenko ◽  
Oleg Shekhtman ◽  
Anton Konovalov

OBJECT Thrombosis of the cerebral arteries is one of the complications of microsurgical operations for partially thrombosed intracranial aneurysms. The object of this study was to assess the frequency of intraoperative arterial thrombosis (IAT) during microsurgical treatment of large and giant partially thrombosed aneurysms of the middle cerebral artery (MCA) and also to assess the efficacy of the treatment of this complication. MATERIALS The authors analyzed a consecutive series of 53 patients who underwent surgery for partially thrombosed aneurysms of the MCA at the Burdenko Neurosurgical Institute between January 2005 and September 2014. Thirty-two patients had large aneurysms (15–25 mm) and 21 had giant aneurysms (> 25 mm). Clipping of aneurysms was performed in 47 patients, trapping was performed in 3, and wrapping was performed in 3. RESULTS IAT was diagnosed in 10 patients (18.9%). The authors describe a technique for IAT reversal involving the injection of modified human recombinant prourokinase (mr-proUK). Of the 7 patients who underwent injection of mr-proUK in the thrombosed artery, 5 (71.4%) were discharged without any change in neurological status, 1 (14.3%) experienced moderate deterioration (modified Rankin Scale [mRS] score of 2), and 1 (14.3%) experienced severe deterioration (mRS score of 4). Among the 3 patients who had complications and did not receive an injection of mr-proUK, 2 experienced severe deterioration (mRS score of 3 and 4) and 1 had moderate deterioration (mRS score of 2). CONCLUSIONS The primary risk factor of thrombectomy with temporary trapping is thrombosis in the MCA branches. The injection of a fibrinolytic agent into thrombosed MCA branches is an effective method for the treatment of IAT.


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