Dataset Information

Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model.

ABSTRACT:

Background

Intra-arterial (IA) administration of rt-PA for ischemic stroke has the potential for greater thrombolytic efficacy, especially for a large thrombus in the M1 or M2 segment of the middle cerebral artery (MCA). Intracranial hemorrhage (ICH) is a concern with IA or intravenous (IV) administration especially as the therapeutic window is extended. However, because IA administration delivers a higher local concentration of agent, the incidence and severity of ICH may be greater than with similar doses IV. We investigated the safety of rt-PA administration by IA compared to IV infusion following 6 hours of MCA occlusion (MCAo) with reflow in the spontaneously hypertensive rat (SHR).

Methods

Male SHRs were subjected to 6 hours MCAo with 18 hours reflow using a snare ligature model. They were treated with IA saline, IA rt-PA (1, 5, 10, 30 mg/kg), or IV rt-PA (10 and 30 mg/kg) by a 10 to 60 minute infusion beginning approximately 1 minute before reflow. The rats were recovered for 24 hours after MCAo onset at which time Bleeding Score, infarct volume, and Modified Bederson Score were measured.

Results

Greater hemorrhagic transformation occurred with 10 and 30 mg/kg rt-PA administered IA than IV. The IV 10 mg/kg rt-PA dosage induced significantly less bleeding than did the 1 or 5 mg/kg IA groups. No significant increase in infarct volume was observed after IA or IV treatment. Rats treated with 30 mg/kg rt-PA by either the IA or IV route had greater neurological dysfunction compared to all other groups.

Conclusions

Administration of rt-PA by the IA route following 6 hours of MCAo results in greater ICH and worse functional recovery than comparable dosages IV. Significantly greater bleeding was observed when the IA dose was a tenth of the IV dose. The increased bleeding did not translate in larger infarct volumes.

SUBMITTER: Crumrine RC

PROVIDER: S-EPMC3184064 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Publications

Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model.

Crumrine R Christian RC Marder Victor J VJ Taylor G McLeod GM Lamanna Joseph C JC Tsipis Constantinos P CP Scuderi Philip P Petteway Stephen R SR Arora Vikram V

Experimental & translational stroke medicine 20110920 1

<h4>Background</h4>Intra-arterial (IA) administration of rt-PA for ischemic stroke has the potential for greater thrombolytic efficacy, especially for a large thrombus in the M1 or M2 segment of the middle cerebral artery (MCA). Intracranial hemorrhage (ICH) is a concern with IA or intravenous (IV) administration especially as the therapeutic window is extended. However, because IA administration delivers a higher local concentration of agent, the incidence and severity of ICH may be greater tha ...[more]

PMID: 21933438

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Project description:ObjectiveTo evaluate the clinical efficacy of intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke.MethodsA total of 76 patients with acute ischemic stroke admitted to the Encephalopathy Dept. of Zhecheng Hospital of Traditional Chinese Medicine between February 2021 and June 2022 were recruited in this prospective trial (ClinicalTrials.gov, NCT03884410) and patients were randomized 1:1 to receive either aspirin plus clopidogrel (control group) or aspirin plus clopidogrel and rt-PA intravenous thrombolytic therapy (experimental group), with 38 cases in each group. The treatment efficiency, National Institute of Health stroke scale (NIHSS) scores, daily living ability, coagulation function, serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2), homocysteine (HCY), hypersensitive C-reactive protein (hsCRP) levels, adverse events, and prognosis were evaluated and compared between the two groups.ResultsIntravenous thrombolysis with rt-PA resulted in a better treatment outcome of patients versus aspirin plus clopidogrel (P<0.05). Patients with rt-PA exhibited better improvement in neurological function than those with aspirin plus clopidogrel, as shown by the lower NIHSS scores (P<0.05). Intravenous thrombolysis with rt-PA resulted in a better quality of life of patients than aspirin plus clopidogrel, indicated by the higher Barthel Index (BI) levels (P<0.05). The lower von Willebrand factor (vWF) and Factor VIII (F) levels indicated better coagulation function of patients with rt-PA versus those with aspirin plus clopidogrel (P<0.05). The lower serum concentrations of Lp-PLA2, HCY, and hsCRP suggested patients with rt-PA had milder inflammatory responses versus those without rt-PA (P<0.05). There was no significant difference in the incidence of adverse events in the two groups (P>0.05). Intravenous thrombolytic therapy with rt-PA better enhanced the prognosis of patients than with aspirin plus clopidogrel (P<0.05).ConclusionCompared with conventional pharmacological regimens, additional rt-PA intravenous thrombolytic therapy improves the clinical outcome of patients with acute ischemic stroke, promotes neurological recovery, and enhances patient prognosis without increasing the risk of patient-related adverse events.

Project description:BACKGROUND:The necessity for rapid evaluation and treatment of acute ischemic stroke with intravenous tPA (tissue-type plasminogen activator) may increase the risk of administrating tPA to patients presenting with noncerebrovascular conditions that closely resemble stroke (stroke mimics). However, there are limited data on thrombolysis safety in stroke mimics. METHODS AND RESULTS:Using data from the Get With The Guidelines-Stroke Registry, we identified 72?582 patients with suspected ischemic stroke treated with tPA from 485 US hospitals between January 2010 and December 2017. We documented the use of tPA in stroke mimics, defined as patients who present with stroke-like symptoms, but after workup are determined not to have suffered from a stroke or transient ischemic attack, and compared characteristics and outcomes in stroke mimics versus those with ischemic stroke. Overall, 3.5% of tPA treatments were given to stroke mimics. Among them, 38.2% had a final nonstroke diagnoses of migraine, functional disorder, seizure, and electrolyte or metabolic imbalance. Compared with tPA-treated true ischemic strokes, tPA-treated mimics were younger (median 54 versus 71 years), had a less severe National Institute of Health Stroke Scale (median 6 versus 8), and a lower prevalence of cardiovascular risk factors, except for a higher prevalence of prior stroke/transient ischemic attack (31.3% versus 26.1%, all P<0.001). The rate of symptomatic intracranial hemorrhage was lower in stroke mimics (0.4%) as compared with 3.5% in ischemic strokes (adjusted odds ratio, 0.29; 95% CI, 0.17-0.50). In-hospital mortality rate was significantly lower in stroke mimics (0.8% versus 6.2%, adjusted odds ratio, 0.31; 95% CI, 0.20-0.49). Patients with stroke mimics were more likely to be discharged to home (83.8% versus 49.3%, adjusted odds ratio, 2.97; 95% CI, 2.59-3.42) and to ambulate independently at discharge (78.6% versus 50.6%, adjusted odds ratio, 1.86; 95% CI, 1.61-2.14). CONCLUSIONS:In this large cohort of patients treated with tPA, relatively few patients who received tPA for presumed stroke were ultimately not diagnosed with a stroke or transient ischemic attack. The complication rates associated with tPA in stroke mimics were low. Despite the potential risk of administering tPA to stroke mimics, opportunity remains for continued improvement in the rapid and accurate diagnosis and treatment of ischemic stroke.

Dataset Information

Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model.

Background

Methods

Results

Conclusions

Publications

Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model.

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