scholarly journals Effect of Delayed Thrombolysis with rt-PA in a Rat Embolic Stroke Model

1994 ◽  
Vol 14 (3) ◽  
pp. 472-477 ◽  
Author(s):  
Karsten Overgaard ◽  
Tomas Sereghy ◽  
Hans Pedersen ◽  
Gudrun Boysen

The effect of delayed thrombolysis with recombinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embolized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15–240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56–71% after embolization. Reperfusion induced by thrombolytic therapy was demonstrated by comparing the posttreatment angiography of the pooled five treatment groups to control animals. Thrombolytic therapy significantly reduced the infarct volume and improved the prekill clinical score by up to 2 h of treatment delay, and treatment might have been beneficial even after 4 h delay. Prolonging the delay of treatment increased the infarct volume ( p < 0.001, Jonckheere–Terpstra test). Only a few hemorrhagic complications were observed. Thus, thrombolytic therapy in embolic stroke induced recanalization. The effect on clinical outcome and infarct volume was dependent on delay time.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tao Peng ◽  
George L Britton ◽  
Jaroslaw Aronowski ◽  
Davide Cattano ◽  
Melvin E Klegerman ◽  
...  

BACKGROUND: Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. Intravenous (iv) tissue plasminogen activator (tPA) in combination with the neuroprotective gas, xenon (Xe), is a promising strategy for ischemic stroke treatment. However, Xe delivery by inhalation may reduce oxygen uptake and tPA activity. We have developed novel Xe-containing echogenic liposomes (Xe-ELIP). In this study, we investigated the therapeutic effect of Xe-ELIP in a rat embolic stroke model. METHODS: Xe-ELIP was prepared by the pressurized-freeze method. Thrombotic strokes were induced in male Sprague-Dawley rats (n=16) by injecting a 13mm long blood clot into the middle cerebral artery (MCA). In the treatment group, tPA (10mg/kg) was infused intravenously at 2 hours after the onset occlusion. Xe-ELIP was administrated into the common carotid artery just before iv tPA. Continuous wave ultrasound (1 MHz, 50% duty cycle, 0.5 W/cm 2 ) was applied to trigger Xe release from ELIP during the 5 min of Xe-ELIP administration. Behavioral tests (limb placement, grid walking and beam walking) were conducted three days after the thrombotic stroke. Two mm-thick coronal brain sections were cut and stained with TTC to determine infarct size. RESULTS: The thrombotic stroke control group without any treatment exhibited the largest damage and infarct size (17±5% of the whole brain); tPA treatment reduced the damage and the infarct size to 5.2±0.4% of (p=0.025 vs stroke). tPA treatment in combination with Xe-ELIP further reduced the infarct size to 1.5±0.4% (p=0.05 vs tPA group) ( Fig 1a, 1b). Behavioral deficit correlated with the infarct volume reduction. Regional blood flow velocity monitored by a laser Doppler flow meter was the same in both tPA and tPA+Xe-ELIP treatment groups. CONCLUSIONS: This study has demonstrated a significant neuroprotective effect of ELIP-encapsulated xenon released by application of 1 MHz ultrasound. Xe-ELIP can be used in combination with tPA without affecting tPA thrombolytic activity.


Stroke ◽  
2001 ◽  
Vol 32 (3) ◽  
pp. 748-752 ◽  
Author(s):  
Deborah F. Chapman ◽  
Patrick Lyden ◽  
Paul A. Lapchak ◽  
Sonia Nunez ◽  
Harold Thibodeaux ◽  
...  

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Toshiyuki Ohtani ◽  
Ryosuke Sintoku ◽  
Tasuku Yajima ◽  
Naoyuki Kaneko

Abstract Background Idarucizumab is a specific antidote for the anticoagulant dabigatran. Although its efficacy has been recently reported, the drug is still in postmarketing surveillance and requires case data in different emergency settings. A newer intravenous thrombolytic therapy with recombinant tissue plasminogen activator has been proposed after injection of idarucizumab in patients receiving dabigatran; however, the safety and efficacy of this therapy are equivocal because of the limited number of reported cases. We describe a case of a patient with acute lacunar stroke causing dysarthria and hemiparesis successfully treated with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab. Case presentation A 67-year-old Asian woman was transferred to our emergency center 200 minutes after sudden onset of dysarthria and right-sided hemiparesis. She had been taking dabigatran for prevention of stroke recurrence caused by atrial fibrillation. Diffusion-weighted magnetic resonance imaging revealed a new lacunar infarction near old putamen infarctions. We treated her with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after administering idarucizumab. The time to recombinant tissue plasminogen activator administration was 5 minutes from idarucizumab injection and 269 minutes from symptom onset. The patient’s activated partial thromboplastin times were 68.0 and 43.2 seconds before and after the therapy, respectively. The patient’s neurological symptoms improved significantly after the treatment, and she experienced no adverse events. Conclusions Intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab may be safe and feasible in patients with acute ischemic stroke with lacunar infarct. Furthermore, intravenous thrombolytic therapy with recombinant tissue plasminogen activator could be used in patients in emergency settings until just before the end of the recommended time limit within which it needs to be administered because of the immediate effect of idarucizumab.


1989 ◽  
Vol 25 (3) ◽  
pp. 281-285 ◽  
Author(s):  
David A. Phillips ◽  
Marc Fisher ◽  
Thomas W. Smith ◽  
Michael A. Davis ◽  
Roy H. L. Pang

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