Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage

Edema reduction and blood-brain barrier protection

Kenneth R. Wagner, Guohua Xi, Ya Hua, Mario Zuccarello, Gabrielle M. De Courten-Myers, Joseph P. Broderick, Thomas G Brott

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs. Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0,3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post- ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 ± 1.3 to 2.8 ± 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 ± 0.10 compared with 1.26 ± 0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28 ± 0.05 compared with 1.46 ± 0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls. Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalJournal of Neurosurgery
Volume90
Issue number3
StatePublished - Mar 1999

Fingerprint

Cerebral Hemorrhage
Tissue Plasminogen Activator
Blood-Brain Barrier
Edema
Swine
Fibrinolytic Agents
Hematoma
Animal Models
Clinical Trials

Keywords

  • Blood-brain barrier
  • Cerebral hemorrhage
  • Edema
  • Fibrinolysis
  • Pig
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage : Edema reduction and blood-brain barrier protection. / Wagner, Kenneth R.; Xi, Guohua; Hua, Ya; Zuccarello, Mario; De Courten-Myers, Gabrielle M.; Broderick, Joseph P.; Brott, Thomas G.

In: Journal of Neurosurgery, Vol. 90, No. 3, 03.1999, p. 491-498.

Research output: Contribution to journalArticle

Wagner, Kenneth R. ; Xi, Guohua ; Hua, Ya ; Zuccarello, Mario ; De Courten-Myers, Gabrielle M. ; Broderick, Joseph P. ; Brott, Thomas G. / Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage : Edema reduction and blood-brain barrier protection. In: Journal of Neurosurgery. 1999 ; Vol. 90, No. 3. pp. 491-498.
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abstract = "Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs. Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0,3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post- ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 ± 1.3 to 2.8 ± 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 ± 0.10 compared with 1.26 ± 0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28 ± 0.05 compared with 1.46 ± 0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls. Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70{\%}), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.",
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T1 - Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage

T2 - Edema reduction and blood-brain barrier protection

AU - Wagner, Kenneth R.

AU - Xi, Guohua

AU - Hua, Ya

AU - Zuccarello, Mario

AU - De Courten-Myers, Gabrielle M.

AU - Broderick, Joseph P.

AU - Brott, Thomas G

PY - 1999/3

Y1 - 1999/3

N2 - Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs. Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0,3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post- ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 ± 1.3 to 2.8 ± 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 ± 0.10 compared with 1.26 ± 0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28 ± 0.05 compared with 1.46 ± 0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls. Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.

AB - Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs. Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0,3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post- ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 ± 1.3 to 2.8 ± 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 ± 0.10 compared with 1.26 ± 0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28 ± 0.05 compared with 1.46 ± 0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls. Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.

KW - Blood-brain barrier

KW - Cerebral hemorrhage

KW - Edema

KW - Fibrinolysis

KW - Pig

KW - White matter

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