title: Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation.
abstract: OBJECTIVE
  Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume.
  
  
  METHODS
  A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43+/-0.42 ml on Day 0 to 0.85+/-0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 +/- 0.28 ml on Day 0 to 0.52 +/- 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 +/- 0.61 ml to 1.73 +/- 0.73 ml on Day 4, before dropping to 1.17 +/- 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 +/- 0.21 ml on Day 0 to 1.93 +/- 0.79 ml on Day 4, and further to 3.34 +/- 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04).
  
  
  CONCLUSIONS
  Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.
authors.affiliation: Department of Neurosurgery, Aachen University, Germany. vrohde@ukaachen.de
authors.forename: Veit
authors.initials: V
authors.lastname: Rohde
authors.forename: Ina
authors.initials: I
authors.lastname: Rohde
authors.forename: Ruth
authors.initials: R
authors.lastname: Thiex
authors.forename: Azize
authors.initials: A
authors.lastname: Ince
authors.forename: Axel
authors.initials: A
authors.lastname: Jung
authors.forename: Gregor
authors.initials: G
authors.lastname: Dückers
authors.forename: Klaus
authors.initials: K
authors.lastname: Gröschel
authors.forename: Carina
authors.initials: C
authors.lastname: Röttger
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Küker
authors.forename: Harald D
authors.initials: HD
authors.lastname: Müller
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Gilsbach
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006406:Hematoma / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D013552:Swine; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014619:Vacuum Curettage
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator