The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.

Hematoma puncture, fibrinolysis, and aspiration of the liquefied clot is a promising new treatment strategy for large intracerebral hemorrhages (ICH). Characteristics of the cellular injury and neuronal and glial cell death associated with ICH and the administration of fibrinolytic agents still need...

Full description

Bibliographic Details
Main Authors: Thiex, R, Küker, W, Müller, H, Rohde, I, Schröder, J, Gilsbach, J, Rohde, V
Format: Journal article
Language:English
Published: 2003
_version_ 1797088472728600576
author Thiex, R
Küker, W
Müller, H
Rohde, I
Schröder, J
Gilsbach, J
Rohde, V
author_facet Thiex, R
Küker, W
Müller, H
Rohde, I
Schröder, J
Gilsbach, J
Rohde, V
author_sort Thiex, R
collection OXFORD
description Hematoma puncture, fibrinolysis, and aspiration of the liquefied clot is a promising new treatment strategy for large intracerebral hemorrhages (ICH). Characteristics of the cellular injury and neuronal and glial cell death associated with ICH and the administration of fibrinolytic agents still need to be defined. We developed a porcine model to study the histopathological effects of recombinant tissue-Plasminogen-Activator (rt-PA) on perihematomatous cell integrity. In 20 pigs, lobar hematomas were induced by intracranial pressure (ICP)-controlled injections of 7.6 +/- 1.6 ml of autologous blood into the white matter of the right frontal hemisphere. In nine animals, the clots were lysed with rt-PA, thereby facilitating aspiration 2 h after hematoma induction. In 11 control pigs, the hematoma resorption followed its natural course. The rate of hematoma reduction and edema formation over 10 days was evaluated on planimetry of the MRI data and correlated to the histopathological changes found at autopsy. Although rt-PA significantly accelerated clot resolution compared to controls (p < 0.02), the increase of perihematomatous edema volume within 10 days was not significantly ameliorated in rt-PA-treated animals compared to controls on MRI. The extent of inflammatory infiltrates on histology was more pronounced in animals treated with rt-PA. In conclusion, despite significant reduction in the size of the hematoma clot liquefication with rt-PA and aspiration invokes a substantial inflammatory response when studied after 10 days and does not result in a reduction of the perihematomatous edema.
first_indexed 2024-03-07T02:50:35Z
format Journal article
id oxford-uuid:ad8d857a-98f1-45d5-bc25-c006c6629996
institution University of Oxford
language English
last_indexed 2024-03-07T02:50:35Z
publishDate 2003
record_format dspace
spelling oxford-uuid:ad8d857a-98f1-45d5-bc25-c006c66299962022-03-27T03:36:22ZThe long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ad8d857a-98f1-45d5-bc25-c006c6629996EnglishSymplectic Elements at Oxford2003Thiex, RKüker, WMüller, HRohde, ISchröder, JGilsbach, JRohde, VHematoma puncture, fibrinolysis, and aspiration of the liquefied clot is a promising new treatment strategy for large intracerebral hemorrhages (ICH). Characteristics of the cellular injury and neuronal and glial cell death associated with ICH and the administration of fibrinolytic agents still need to be defined. We developed a porcine model to study the histopathological effects of recombinant tissue-Plasminogen-Activator (rt-PA) on perihematomatous cell integrity. In 20 pigs, lobar hematomas were induced by intracranial pressure (ICP)-controlled injections of 7.6 +/- 1.6 ml of autologous blood into the white matter of the right frontal hemisphere. In nine animals, the clots were lysed with rt-PA, thereby facilitating aspiration 2 h after hematoma induction. In 11 control pigs, the hematoma resorption followed its natural course. The rate of hematoma reduction and edema formation over 10 days was evaluated on planimetry of the MRI data and correlated to the histopathological changes found at autopsy. Although rt-PA significantly accelerated clot resolution compared to controls (p < 0.02), the increase of perihematomatous edema volume within 10 days was not significantly ameliorated in rt-PA-treated animals compared to controls on MRI. The extent of inflammatory infiltrates on histology was more pronounced in animals treated with rt-PA. In conclusion, despite significant reduction in the size of the hematoma clot liquefication with rt-PA and aspiration invokes a substantial inflammatory response when studied after 10 days and does not result in a reduction of the perihematomatous edema.
spellingShingle Thiex, R
Küker, W
Müller, H
Rohde, I
Schröder, J
Gilsbach, J
Rohde, V
The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title_full The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title_fullStr The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title_full_unstemmed The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title_short The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.
title_sort long term effect of recombinant tissue plasminogen activator rt pa on edema formation in a large animal model of intracerebral hemorrhage
work_keys_str_mv AT thiexr thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT kukerw thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT mullerh thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT rohdei thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT schroderj thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT gilsbachj thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT rohdev thelongtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT thiexr longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT kukerw longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT mullerh longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT rohdei longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT schroderj longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT gilsbachj longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage
AT rohdev longtermeffectofrecombinanttissueplasminogenactivatorrtpaonedemaformationinalargeanimalmodelofintracerebralhemorrhage