Abstract WP79: Appropriate Timing of Fluoxetine and Statin Administration Reduces the Risk of Secondary Hemorrhagic Infarct After Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Moner A Ragas ◽  
Maria H Balch ◽  
Danny Wright ◽  
Amber Hensley ◽  
Kenny Reynolds ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ischemic Stroke ◽  
Infarct Volume ◽  
Stroke Onset ◽  
Sprague Dawley ◽  
Stroke Patients ◽  
Unequal Variances ◽  
Exact Test ◽  
Strong Trend ◽  
Sprague Dawley Rats

Introduction: Ongoing clinical trials are testing the effect of fluoxetine delivered 2-15 days from the onset of an acute ischemic stroke where a majority of patients are taking statins. We hypothesized that earlier drug delivery would result in smaller infarcts. Methods: Endothelin-1-induced strokes were initiated in 10-12 month old Sprague-Dawley rats, targeting the forelimb motor cortex. Combined medications of 5 mg/kg fluoxetine and 1 mg/kg simvastatin were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and continued daily for 90 days. Infarct volumes were assessed at post-stroke day 91 using Nissl stained coronal brain sections. An unpaired T-test with Welch’s correction for unequal variances was used for statistical comparison of the infarct volumes. Results: Control animals typically had 5-13 mm3 infarct volumes. Animals that received fluoxetine and simvastatin beginning 20-26 hours after stroke induction showed a strong trend of reduced infarct volume (3 ± 0.3447 mm3 SEM, P=0.0563). Earlier drug delivery (6-12 hours after stroke) resulted in significantly larger infarct volumes (15.4 ± 4.260 mm3 SEM, P=0.0157) when the drug groups were directly compared (Fig.1). Examination of the infarct volumes showed that earlier drug delivery induced secondary hemorrhagic infarcts, while later delivery did not (P=0.0427; Fisher’s exact test). Conclusions: There appears to be substantial danger of developing hemorrhagic infarct if the combination of fluoxetine and statin is given within 6-12 hours of stroke induction (RR= 4.36, 95% CI = 0.64-29.5). For that reason, it is crucial to monitor stroke patients for statins and fluoxetine, and withhold the statin for at least 20 hours after stroke onset. Delivery of both drugs after 20-26 hours of stroke onset resulted in significantly reduced infarcts.

scholarly journals Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun Han ◽  
Xiao-kun Geng ◽  
Hangil Lee ◽  
Fengwu Li ◽  
Yuchuan Ding
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Glucose Transporter ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Ros Production ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Neuroprotective Effects ◽  
Sprague Dawley Rats

Background and Purpose. Studies have shown that interischemia hypothermia is able to reduce the size of myocardial infarctions and improve their clinical outcomes. The present study determined whether interischemia hypothermia induced by the pharmacological approach induced stronger neuroprotection in ischemic brains. Methods. Adult male Sprague Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (interischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin (DHC) was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the interischemia and inter-reperfusion groups, brain damage was evaluated using infarct volume and neurological deficits at 24 h reperfusion. In addition, mRNA expressions of NADPH oxidase (NOX) subunits (gp91phox, p67phox, p47phox, and p22phox) and glucose transporter subtypes (GLUT1 and GLUT3) were determined by real-time PCR at 6 and 24 h reperfusion. ROS production was measured by flow cytometry assay at the same time points. Results. In both hypothermia groups, the cerebral infarct volumes and neurological deficits were reduced in the ischemic rats. At 6 and 24 h reperfusion, ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by interischemia hypothermia at 24 h. Conclusion. Both interischemia and inter-reperfusion pharmacological hypothermia treatments play a role in neuroprotection after stroke. Interischemia hypothermia treatment may be better able to induce stronger neuroprotection after ischemic stroke. This study provides a new avenue and reference for stronger neuroprotective hypothermia before vascular recanalization in stroke patients.

Abstract 178: Infarct Growth Rate Depends on Collateral Status in Acute Ischemic Stroke Patients

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Reza Hakimelahi ◽  
Karen A Buch ◽  
Thabele M Leslie-Mazwi ◽  
Joshua A Hirsch ◽  
James D Rabinov ◽  
...  
Keyword(s):  
Growth Rate ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Time Windows ◽  
Treatment Options ◽  
Contralateral Side ◽  
Stroke Onset ◽  
Lesion Volume ◽  
Stroke Patients

Introduction and Hypothesis: Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but < contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis. Results: In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p<0.0004 for all group comparisons). Patients with good collaterals were younger (p=0.004 and p=0.018 compared to poor and intermediate groups respectively) and had lower NIHSS scores (p< 0.001). Time after stroke onset, gender, or occlusion site (ICA vs MCA) were not significantly different among different collateral groups. There was no correlation between time and DWI volume (r2=0.02, p=0.8) or collateral status (r2=0.05, p=0.6). There was significant correlation between collateral status and infarct growth (r2=-0.6,p<0.0001). Conclusion: AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.

scholarly journals Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Focused Ultrasound ◽  
Healthy Tissue ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Intense Staining ◽  
Her2 Breast Cancer ◽  
Sprague Dawley Rats ◽  
Blood Spinal Cord Barrier

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hannah J Irvine ◽  
Thomas W Battey ◽  
Ann-Christin Ostwaldt ◽  
Bruce C Campbell ◽  
Stephen M Davis ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Edema ◽  
Infarct Volume ◽  
Brain Magnetic Resonance Imaging ◽  
Lesion Volume ◽  
Stroke Patients ◽  
Early Reperfusion ◽  
Echoplanar Imaging ◽  
Swelling Volume

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.

Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
The United States ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Increased Risk ◽  
Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Abstract TP315: D-dimer is Associated With 30-day Mortality in Acute Ischemic Stroke With Active Cancer

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ki Woong Nam ◽  
Chi Kyung Kim ◽  
Tae Jung Kim ◽  
Sang Joon An ◽  
Kyungmi Oh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Nihss Score ◽  
Patients With Cancer ◽  
Advanced Stages ◽  
D Dimer ◽  
Active Cancer

Background: Stroke in cancer patients is not rare, but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. Methods: We included 210 ischemic stroke patients with active cancer. The data of 30-day mortality were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. Results: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS score, D-dimer levels, CRP levels, frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. Initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independently from D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease of D-dimer levels, despite treatment, while the survivor group showed opposite responses. Conclusions: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

scholarly journals Erratum to: Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume

2011 ◽  
Vol 259 (2) ◽  
pp. 400-400 ◽  
Author(s):  
Heidi Ormstad ◽  
Hans Christian Dalsbotten Aass ◽  
Niels Lund-Sørensen ◽  
Karl-Friedrich Amthor ◽  
Leif Sandvik
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Serum Levels ◽  
C Reactive Protein ◽  
Stroke Patients ◽  
Reactive Protein

scholarly journals Emergency Medical Services Support for Acute Ischemic Stroke Patients Receiving Thrombolysis at a Primary Stroke Center

2009 ◽  
Vol 1 ◽  
pp. JCNSD.S2221
Author(s):  
Byron R. Spencer ◽  
Omar M. Khan ◽  
Bentley J. Bobrow ◽  
Bart M. Demaerschalk
Keyword(s):  
Decision Making ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Stroke Onset ◽  
Stroke Patients ◽  
Emergency Medical ◽  
Field Assessment ◽  
Primary Stroke Center ◽  
Stroke Center

Background Emergency Medical Services (EMS) is a vital link in the overall chain of stroke survival. A Primary Stroke Center (PSC) relies heavily on the 9-1-1 response system along with the ability of EMS personnel to accurately diagnose acute stroke. Other critical elements include identifying time of symptom onset, providing pre-hospital care, selecting a destination PSC, and communicating estimated time of arrival (ETA). Purpose Our purpose was to evaluate the EMS component of thrombolysed acute ischemic stroke patient care at our PSC. Methods In a retrospective manner we retrieved electronic copies of the EMS incident reports for every thrombolysed ischemic stroke patient treated at our PSC from September 2001 to August 2005. The following data elements were extracted: location of victim, EMS agency, times of dispatch, scene, departure, emergency department (ED) arrival, recordings of time of stroke onset, blood pressure (BP), heart rate (HR), cardiac rhythm, blood glucose (BG), Glasgow Coma Scale (GCS), Cincinnati Stroke Scale (CSS) elements, emergency medical personnel field assessment, and transport decision making. Results Eighty acute ischemic stroke patients received thrombolysis during the study interval. Eighty-one percent arrived by EMS. Two EMS agencies transported to our PSC. Mean dispatch-to-scene time was 6 min, on-scene time was 16 min, transport time was 10 min. Stroke onset time was recorded in 68%, BP, HR, and cardiac rhythm each in 100%, BG in 81%, GCS in 100%, CSS in 100%, and acute stroke diagnosis was made in 88%. Various diagnostic terms were employed: cerebrovascular accident in 40%, unilateral weakness or numbness in 20%, loss of consciousness in 16%, stroke in 8%, other stroke terms in 4%. In 87% of incident reports there was documentation of decision-making to transport to the nearest PSC in conjunction with pre-notification. Conclusion The EMS component of thrombolysed acute ischemic stroke patients care at our PSC appeared to be very good overall. Diagnostic accuracy was excellent, field assessment, decision-making, and transport times were very good. There was still room for improvement in documentation of stroke onset and in employment of a common term for acute stroke.

Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke

2020 ◽  
pp. 1-9
Author(s):  
Mahesh Kate ◽  
Laura Gioia ◽  
Negar Asdaghi ◽  
Thomas Jeerakathil ◽  
Ashfaq Shuaib ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cerebral Perfusion ◽  
Primary Outcome ◽  
Infarct Volume ◽  
Univariate Analysis ◽  
Primary Outcome Measure ◽  
Untreated Group ◽  
Stroke Patients ◽  
The Mean

ABSTRACT: Objective: The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. Patients and methods: Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. Results: The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5–49.3) ml in the NTG group and 32.6 (8.6–96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7–44.2) ml) than the NTG group (3.2 (0.5–16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. Conclusion: NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

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