Abstract
We assessed the incidence of hemorrhagic transformation and infarct volume after early
intravenous infusion of recombinant human tissue plasminogen activator (rht-PA) in
a newly developed rat cerebral embolic model. Male Wistar rats (n=60) were subjected to middle cerebral artery (MCA) occlusion by a single fibrin rich
clot. One hour after embolization, rats were assigned to the following groups: (1)
rht-PA treated group (n=20); (2) vehicle treated group (n=20); and (3) saline treated group (n=20). Neurological deficits, lodgement of a clot at the origin of the MCA, infarction
volume and microscopic hemorrhage were measured. Animals exhibited moderate to severe
neurological deficits 1 h after MCA occlusion in all groups. Administration of rht-PA
significantly (P<0.05) reduced the incidence of lodgement of a clot at the origin of the MCA (30%)
compared with the saline treated group (100%) and the vehicle treated group (80%).
A significant (P<0.05) reduction of percent hemispheric infarct volume was detected between the saline
(33.2±3.71%) and the rht-PA groups (19.4±3.3%). However, no significant difference
was found in the total area of microscopic hemorrhage of the rht-PA (0.05±0.02 mm2), the vehicle (0.02±0.01 mm2), and the saline (0.03±0.02 mm2) treated groups. No significant difference of percent hemispheric infarct volume
(P=0.08) was observed between the vehicle and the rht-PA treated groups. This study
demonstrates that treatment with rht-PA reduced infarct volume without increasing
intracerebral hemorrhage in rats with large cerebral infarction when treatment was
initiated at 1 h of the onset of embolization.
Keywords
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References
Anderson JL, Karagounis L, Allen A, Bradford MJ, Menlove RL, Pryor TA. Older age and elevated blood pressure are risk factors for intracerebral hemorrhage after thrombolysis. Am J Cardiol 1991;15(68):166–70.
- Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction.Stroke. 1990; 21: 596-601
- Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.Ann Neurol. 1992; 32: 78-86
- Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study.J Am Med Assoc. 1995; 274: 1017-1025
- `Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs.Arch Neurol. 1996; 53: 309-315
- Hemorrhagic transformation and microvascular integrity during focal cerebral ischemia/reperfusion.J Cereb Blood Flow Metab. 1996; 16: 1373-1378
- A comparison of intra-arterial and intravenous tissue-type plasminogen activator on autologous arterial emboli in the cerebral circulation of rabbits.Stroke. 1994; 25: 651-656
- Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion.J Cereb Blood Flow Metab. 1997; 17: 388-400
- Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient (2 h) but not after permanent MCA occlusion in the rat.Neurosci Res Comm. 1994; 15: 85-93
- Evaluation of cerebral artery embolic stroke and rt-PA intervention using diffusion, perfusion and T2 weighted NMR imaging in rat.J Cereb Blood Flow Metab. 1997; 17: S326
- Ischaemic cerebrovascular diseases in an autopsy series. 2. Prevalence, location, pathogenesis, and clinical course of cerebral infarcts..J Neurol Sci. 1969; 9: 285-320
- Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study.Stroke. 1997; 28: 957-960
- Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke.Stroke. 1994; 25: 291-297
- Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence.Cerebrovasc Brain Metab Rev. 1993; 5: 1-16
- Intracerebral hemorrhage after experimental embolic infarction.Arch Neuro. 1987; 44: 848-850
- L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat.Stroke. 1994; 25: 429-435
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–7.
- Reduction of infarct volume by thrombolysis with rt-PA in an embolic rat stroke model.Scand J Clin Invest. 1993; 53: 383-393
- A rat model of reproducible cerebral infarction using thrombotic blood clot emboli.J Cereb Blood Flow Metab. 1992; 12: 484-490
- Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model.J Cereb Blood Flow Metab. 1994; 14: 472-477
- Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke.J Neurosurg. 1987; 67: 394-398
- The effect of intravenous tissue-type plasminogen activator in a rat model of embolic cerebral ischemia.Yale J Biol Med. 1987; 60: 233-243
- The safety and angiographic efficacy of tissue plasminogen activator in a cerebral embolization model.Ann Neurol. 1988; 23: 391-394
- Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization.Neurology. 1992; 42: 289-298
- Hemorrhagic infarct induced by arterial hypertension in cat brain following middle cerebral artery occlusion.Stroke. 1990; 21: 589-595
- Hemorrhagic complications of thrombolytic therapy in experimental stroke.Stroke. 1987; 18: 1148-1156
- A semiautomated method for measuring brain infarct volume.J Cereb Blood Flow Metab. 1990; 10: 290-293
- A long half-life and fibrin specific form of tissue plasminogen activator in rabbit models of embolic stroke and peripheral bleeding.Stroke. 1994; 25: 2072-2078
- Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke. 1989; 20: 84-91
- A rat model of focal embolic cerebral ischemia.Brain Res. 1997; 766: 83-92
- Tissue plasminogen activator reduces neurological damage after cerebral embolism.Science. 1985; 230: 1289-1292
- Tissue plasminogen activator. Reduction of neurologic damage after experimental embolic stroke.Arch Neurol. 1988; 45: 387-391
Article info
Publication history
Accepted:
April 3,
1998
Received in revised form:
March 18,
1998
Received:
October 31,
1997
Identification
Copyright
© 1998 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
