scholarly journals Reperfusion failure despite recanalization in stroke: New translational evidence

2021 ◽  
Vol 5 (1) ◽  
pp. 2514183X2110071
Author(s):  
Mohamad El Amki ◽  
Susanne Wegener
Keyword(s):  
Mechanical Thrombectomy ◽  
Recombinant Tissue Plasminogen Activator ◽  
Current Treatment ◽  
Stroke Patients ◽  
Ischemic Brain ◽  
Clot Removal ◽  
Luminal Narrowing ◽  
Thrombolytic Drug ◽  
Tissue Plasminogen ◽  
Ischemic Brain Tissue

Current treatment for acute ischemic stroke aims at recanalizing the occluded blood vessel to reperfuse ischemic brain tissue. Clot removal can be achieved pharmacologically with a thrombolytic drug, such as recombinant tissue plasminogen activator, or with mechanical thrombectomy. However, reopening the occluded vessel does not guarantee full tissue reperfusion, which has been referred to as reperfusion failure. When it occurs, reperfusion failure significantly attenuates the beneficial effect of recanalization therapy and severely affects functional recovery of stroke patients. The mechanisms of reperfusion failure are somewhat complex and not fully understood. Briefly, after stroke, capillaries show stalls, constriction and luminal narrowing, being crowded with neutrophils, and fibrin–platelet deposits. Furthermore, after recanalization in stroke patients, a primary clot can break, dislodge, and occlude distal arterial branches further downstream. In this review, we highlight a rodent model that allows studying the pathophysiological mechanisms underlying reperfusion failure after stroke. We also describe the vascular and intravascular changes involved in reperfusion, which may provide relevant therapeutic targets for improving treatment of stroke patients.

Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke

2012 ◽  
Vol 112 (12) ◽  
pp. 2068-2076 ◽  
Author(s):  
H. N. David ◽  
B. Haelewyn ◽  
M. Degoulet ◽  
D. G. Colomb ◽  
J. J. Risso ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Rat Model ◽  
Recombinant Tissue Plasminogen Activator ◽  
Thromboembolic Stroke ◽  
Stroke Patients ◽  
Ischemic Brain ◽  
Normobaric Oxygen ◽  
Tissue Plasminogen ◽  
Flow Restoration

The potential benefit of 100 vol% normobaric oxygen (NBO) for the treatment of acute ischemic stroke patients is still a matter of debate. To advance this critical question, we studied the effects of intraischemic normobaric oxygen alone or in combination with recombinant tissue-plasminogen activator (rtPA) on cerebral blood flow and ischemic brain damage and swelling in a clinically relevant rat model of thromboembolic stroke. We show that NBO provides neuroprotection by achieving cerebral blood flow restoration equivalent to 0.9 mg/kg rtPA through probable direct interaction and facilitation of the fibrinolytic properties of endogenous tPA. In contrast, combined NBO and rtPA has no neuroprotective effect on ischemic brain damage despite producing cerebral blood flow restoration. These results 1) by providing a new mechanism of action of NBO highlight together with previous findings the way by which intraischemic NBO shows beneficial action; 2) suggest that NBO could be an efficient primary care therapeutic intervention for patients eligible for rtPA therapy; 3) indicate that NBO could be an interesting alternative for patients not eligible for rtPA therapy; and 4) caution the use of NBO in combination with rtPA in acute stroke patients.

Computed Tomography Angiography in Acute Stroke Patients Receiving Recombinant Tissue Plasminogen Activator: Outcome and Safety Evaluations in an Asian Population

2020 ◽  
Vol 49 (1) ◽  
pp. 62-69
Author(s):  
Chuan-Min Lin ◽  
Hsiu-Chuan Wu ◽  
Yi-Ming Wu ◽  
Chi-Hung Liu ◽  
Kuo-Hsuan Chang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Computed Tomography Angiography ◽  
Mechanical Thrombectomy ◽  
Medical Center ◽  
Asian Population ◽  
Recombinant Tissue Plasminogen Activator ◽  
Stroke Patients ◽  
Tissue Plasminogen

Introduction: The multiphase computed tomography angiography (mCTA) is superior to the noncontrast computed tomography (NCCT) in selecting patients that would benefit from mechanical thrombectomy following an acute ischemic stroke (AIS). It remains unclear whether the longer examination time of mCTA worsens outcomes of intravenous recombinant tissue plasminogen activator (IV r-tPA) or increases the risk of hemorrhagic transformation (HT) compared to NCCT in Asian stroke patients. Methods: Between January 2011 and December 2017, 199 AIS patients receiving IV r-tPA with initial National Institute of Health Stroke Scale (NIHSS) scores between 6 and 25 were enrolled in a single medical center. Onset-to-needle time (ONT), door-to-needle time (DNT), and creatinine levels before and after thrombolysis were recorded. We evaluated NIHSS scores 2, 24 h after treatment, and at discharge, the modified Rankin Scale (mRS) at discharge, and mortality rate. The presence of HT was reviewed within 7 days after thrombolysis. Results: DNT, perithrombolysis creatinine levels, NIHSS, and mRS scores at the emergency room were similar between the NCCT and mCTA groups. ONT was shorter in the mCTA group. AIS patients got more significant neurologic improvement (NIHSS decrease ≥4) after thrombolysis and physically independent (mRS ≤2) at discharge in the mCTA group. Mortality rates, symptomatic, and total HT rates were similar between the NCCT and mCTA groups. Conclusion: Comparing to NCCT, mCTA-based IV r-tPA would not delay DNT nor worsen the outcome. Furthermore, mCTA provides more information for early identification of candidates for mechanical thrombectomy in Asian AIS patients.

scholarly journals Interventional Mechanical thrombectomy Indications and limitations A Mini-Review

2021 ◽  
Vol 9 (4) ◽  
pp. 01-04
Author(s):  
Sheila Fatehpur
Keyword(s):  
Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Time Window ◽  
Recombinant Tissue Plasminogen Activator ◽  
Posterior Circulation ◽  
Large Vessel Occlusion ◽  
Arterial Ischemic Stroke ◽  
Stroke Patients ◽  
Vessel Occlusion ◽  
Tissue Plasminogen

The endovascular clot retrieval in combination with intravenous recombinant tissue plasminogen activator (rtPA) has been established as the 1st choice therapy for the treatment of acute arterial ischemic stroke (AIS) in case of large vessel occlusion. While the results of this therapy in ischemic insults in the anterior stromal region are clearly positive, the results for mechanical thrombectomy in posterior circulation are controversially discussed. In addition, the indication is made by the time window, sizing of the ischemic area, and various scores. The aim of the article is to review the available reports on the use of thromboelastography in acute ischemic stroke patients.

Study on the therapeutic and nursing effect of thrombus targeted thrombolysis mediated by recombinant plasminogen activator modified nanoparticles on stroke patients

2021 ◽  
Vol 11 (7) ◽  
pp. 1024-1030
Author(s):  
Li Zhang ◽  
Miao Xu ◽  
Min Zhu ◽  
Andong Liu ◽  
Fenghua Zhao
Keyword(s):  
Drug Therapy ◽  
Plasminogen Activator ◽  
Survival Rates ◽  
Clinical Applications ◽  
The Self ◽  
Therapeutic Effects ◽  
Stroke Patients ◽  
Traditional Treatment ◽  
Thrombolytic Drug ◽  
Tissue Plasminogen

Tissue plasminogen activator (rt-PA) is a thrombolytic drug used for the treatment of stroke. However, it has a short half-life and a high risk of complications of cerebral hemorrhage, which complicates its use in clinical applications. In this study, polyethylene glycol and polycaprolactone were used as nano-carriers in the development of new nano-drug-recombinant plasminogen activator modified nanoparticles (PEG-PCL@rt-PA) loaded with rt-PA. Following treatment, the patients received with either conventional nursing or continuous nursing. Compared with traditional treatment and nursing, the nanoparticles had stronger thrombolytic and therapeutic effects, significantly improved the self-care recovery rate of patients, and reduced the occurrence of complications. This new mode of PEG-PCL@rt-PA drug therapy combined with continuous nursing is expected to improve the recovery and survival rates of stroke patients.

Abstract T P66: Safety and Effectiveness of Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients on Aspirin and Clopidogrel

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mushtaq H Qureshi ◽  
Shayaan M Khan ◽  
Nauman Jahangir ◽  
Ahmed A Malik ◽  
Melissa Freese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Combination Therapy ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Favorable Outcome ◽  
Stroke Patients ◽  
Neurological Improvement ◽  
Tissue Plasminogen

Background: The number of acute ischemic stroke patients who are on both aspirin and clopidogrel treatment at time of acute ischemic event is increasing. There is limited data regarding the safety and efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) treatment in such patients. Methods: We reviewed the medical records and imaging data of consecutive patients with acute ischemic stroke who received IV rt-PA within 4.5 hours of symptom onset. We stratified the patients based on active regular use of antiplatelet medications: monotherapy (aspirin or clopidogrel), combination therapy (aspirin and clopidogrel), and no therapy and compared the rates of symptomatic intracerebral hemorrhage (ICH), neurological improvement (≥4 points in National Institutes of Health Stroke Scale [NIHSS], and favorable outcome (modified Rankin scale [mRS] 0-1) at discharge between the three groups. Results: A total of 88 acute ischemic stroke patients (mean age±SD; 69.88 ±15) were treated with IV rt-PA within the study duration. Of the 88 patients 45 (50.6%), 37 (41.6%), and 52 (58.4) were on monotherapy, combination therapy, or no therapy at time of presentation. The proportion of patients who developed symptomatic ICHs were similar (p=0.8) in monotherapy, combination therapy, and no therapy groups (3.3%, 0.0%, and 4.1%, respectively). The rates of neurological improvement were greater in patients on monotherapy (20%) (p=0.03) followed by combination therapy (11.1%), and no therapy groups (2.0%). There was no significant reduction in the rate of favorable outcome at discharge among patients on combination treatment compared with no treatment (odds ratio 0.8 , 95% confidence interval 0.4-1.8 ) after adjusting for age and initial NIHSS score strata (<10, 10-19, and ≥20). Conclusions: Compared with patients on no antiplatelet treatment, acute ischemic stroke patients who are actively using aspirin and clopidogrel appear to have similar risks and benefits with IV rt-PA treatment.

Abstract TP10: Intra-Arterial Thrombolysis After Failed Mechanical Thrombectomy: A STRATIS Registry Subgroup Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Syed Zaidi ◽  
Alicia Castonguay ◽  
Mouhammad Jumaa ◽  
Nils Mueller-Kronast ◽  
Osama Zaidat
Keyword(s):  
Mechanical Thrombectomy ◽  
Rescue Therapy ◽  
Recombinant Tissue Plasminogen Activator ◽  
Prospective Data ◽  
Increased Risk ◽  
First Choice ◽  
Tissue Plasminogen ◽  
Symptomatic Intracranial Hemorrhage ◽  
Number Of Passes ◽  
Arterial Thrombolysis

Background: Limited prospective data exists on the use of intra-arterial (IA) thrombolytics as rescue therapy(RT) after failed mechanical thrombectomy(MT) in acute ischemic stroke(AIS) patients with large vessel occlusions LVO). The aim of this study is to investigate the use of IA recombinant tissue plasminogen activator(IA-rtPA) as RT in the prospective STRATIS Registry. Methods: Data from the STRATIS Registry, a multicenter study of AIS patients treated with the Solitaire stent-retriever as the first choice therapy within 8 hours from symptoms onset, were analyzed. Clinical and angiographic outcomes were compared between patients treated with and without IA-rtPA. Both anterior and posterior circulation occlusions were included in this substudy. Results: Of the 938 STRATIS patients with IA-tPA use reported, 809 and 129 were in the no IA-rtPA(83.2%) and IA-rtPA(13.8%)groups, respectively. No difference was seen in baseline demographics. Site of occlusion was similar between the groups, with the majority occurring in the MCA(72.4% versus 73.6%, p=0.74). IV-rtPA was administered in 63.0% and 70.5% of no IA-rtPA and IA-rtPA patients(p=0.11). Median IA-rtPA dose was 4mg(IQR 2-12). Mean onset to arterial puncture time was shorter in the IA-rtPA group(200.2±104.6 versus 228.2±98.5 minutes, p=0.003); however, mean puncture to procedure end time was longer in the IA-rtPA group(78.7±43.1 versus 63.1±35.9 minutes). Mean number of passes (2.2±1.4 versus 1.8±1.2,p=0.001) and rate of distal embolization(67.8% versus 54.5%, p=0.007) was significantly higher in the IA-rtPA group. Core lab adjudicated substantial reperfusion (mTICI≥2b) was achieved in 88.4% and 84.7% of no IA-rtPA and IA-rtPA patients(p=0.16). No difference was observed in rates of symptomatic intracranial hemorrhage(sICH) (1.4% versus 1.6%,p=0.70), good functional outcome (mRS≥2, 57.3% versus 59.2%, p=0.86), or mortality (15.5% versus 13.3%,p=0.80) at 90-days. Conclusion: Use of IA-rtPA after failed thrombectomy was not associated with an increased risk of sICH or mortality in the STRATIS Registry. These results suggest that IA thrombolysis may be a safe option as rescue therapy in select patients.

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