Computer Simulation of Systemic Circulation and Clot Lysis Dynamics During Thrombolytic Therapy That Accounts for Inner Clot Transport and Reaction

Anand, Sriram; Diamond, Scott L.

doi:10.1161/01.cir.94.4.763

Cited by 41 publications

(29 citation statements)

References 50 publications

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“…30 Pressure gradient changes associated with different stroke subtypes may also hamper delivery of the thrombolytic resulting in less exposure and altered responsiveness. 29,31 In addition, the site of the intracranial artery occlusion has been shown to alter the response to thrombolytic agents with terminal internal carotid artery occlusions least likely to respond. 32 An interesting observation from our data is that patients who received rt-PA with a stroke onset between 0401 and 0800 hours were less likely to develop symptomatic ICH in the first 36 hours.…”

Section: Discussionmentioning

confidence: 99%

Time of Day, Outcome, and Response to Thrombolytic Therapy: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trial Experience

Rhoney

Coplin

Yang

et al. 2010

Journal of Stroke and Cerebrovascular Diseases

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Section: Discussionmentioning

confidence: 99%

Time of Day, Outcome, and Response to Thrombolytic Therapy: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trial Experience

Rhoney

Coplin

Yang

et al. 2010

Journal of Stroke and Cerebrovascular Diseases

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“…Following the treatment of Rijken et al 1990 andAnand andDiamond (1996), there are four chemical reactions pertaining to thrombolysis by tPA. These reactions include the activation of plasminogen (Pm) to plasmin (P) by tPA, the inhibition of tPA by plasminogen activator inhibitor 1 (PAI), the inhibition of the resulting plasmin by α 2 antiplasmin (AP) and the degradation of fibrin (F) by plasmin into fibrin degradation products (Fs).…”

Section: Chemical Considerationsmentioning

confidence: 99%

Arrhenius temperature dependence ofin vitrotissue plasminogen activator thrombolysis

et al. 2007

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Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T ≤ 35 °C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Δm(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E eff of 42.0 ± 0.9 kJ mole −1 . E eff approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole −1 . A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.

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“…4,5 However, the time until complete clot dissolution and restoration of blood flow may vary widely, depending on location of occlusion, clot composition, area of clot surface exposed to blood flow, and pressure-driven permeation of tPA into the clot structures. 6,7 Transcranial Doppler (TCD) monitoring provides a noninvasive tool for real-time measurement of the beginning, speed, timing, and degree of recanalization. In unselected stroke patients, the speed of clot lysis during tPA infusion has been demonstrated to predict short-term improvement.…”

mentioning

confidence: 99%

Differential Pattern of Tissue Plasminogen Activator–Induced Proximal Middle Cerebral Artery Recanalization Among Stroke Subtypes

Molina

Montaner

Arenillas

et al. 2004

Stroke

188

144

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Background and Purpose-We aimed to evaluate the timing, speed, and degree of tissue plasminogen activator (tPA)-induced recanalization in patients with proximal middle cerebral artery (MCA) occlusion of different stroke subtypes. Methods-We evaluated 72 patients with acute stroke caused by proximal MCA occlusion treated with intravenous tPA in Ͻ3 hours. Transcranial Doppler monitoring of recanalization was conducted during tPA infusion and at 6 hours. Strokes were categorized as large-vessel disease strokes, cardioembolic strokes, or strokes of undetermined origin according to Trial of Org 10172 in Acute Stroke Treatment criteria. Results-During 1-hour tPA infusion, recanalization occurred in 34 patients (47%); 32% showed a sudden, 50% showed a stepwise, and 18% showed a slow pattern of recanalization. One-hour recanalization was more frequent in patients with cardioembolic stroke (59%) compared with large-vessel disease (8%) and undetermined origin (50%) strokes. A cardiac source of emboli was identified in 81% of patients who showed a sudden clot breakup during tPA infusion. Rate of complete recanalization at 6 hours was higher (Pϭ0.006) in patients with cardioembolic stroke (50%) compared with other stroke subtypes (27%). Sudden recanalization was associated (Pϭ0.002) with a higher degree of neurological improvement at 24 hours compared with stepwise, slow, and no recanalization. A graded response in long-term outcome was observed in relation to the speed of clot lysis during tPA administration. Conclusions-We demonstrate that the pattern of tPA-induced MCA recanalization differs among stroke subtypes. Early recanalization was more frequent, faster, and more complete in patients with cardioembolic stroke compared with other stroke subtypes.

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Computer Simulation of Systemic Circulation and Clot Lysis Dynamics During Thrombolytic Therapy That Accounts for Inner Clot Transport and Reaction

Cited by 41 publications

References 50 publications

Time of Day, Outcome, and Response to Thrombolytic Therapy: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trial Experience

Time of Day, Outcome, and Response to Thrombolytic Therapy: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trial Experience

Arrhenius temperature dependence ofin vitrotissue plasminogen activator thrombolysis

Differential Pattern of Tissue Plasminogen Activator–Induced Proximal Middle Cerebral Artery Recanalization Among Stroke Subtypes

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