Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction.

The effect of an intravenous infusion of recombinant tissue plasminogen activator on hemorrhagic transformation early after middle cerebral artery territory ischemia was studied in an established awake nonhuman primate (baboon) model. Following 3 hours' occlusion of the middle cerebral artery and 30 minutes' reperfusion in each of 30 baboons, a 60-minute infusion of recombinant tissue plasminogen activator (at three doses: Group A, 0.3 mg/kg, n = 6; Group B, 1.5 mg/kg, n = 6; Group C, 10 mg/kg, n = 6) or normal saline (n = 12) was undertaken. The frequency and volume of intracerebral hemorrhage, the volume of infarction, and clinical alterations were determined by computed tomography at 24 hours and 10 days, neuropathology at 14 days, and serial daily neurologic evaluations, respectively. Peripheral (nonintracranial) hemorrhage (Group A, p = 0.46; Group B, p = 0.015; Group C, p = 0.002) and peak plasma tissue plasminogen activator levels varied directly with the dose of recombinant tissue plasminogen activator. Petechial hemorrhagic infarction was a common finding among the 30 baboons. No significant differences in the incidences or volumes of infarction-related hemorrhage were apparent in any group compared with the respective saline-treated baboons. In pooled data, no significant relation between the volume of hemorrhage and the volume of infarction could be established. We conclude that the incidence and severity of hemorrhagic transformation are not related to infarction size and that recombinant tissue plasminogen activator does not increase the incidence or severity (volume) of hemorrhage when given early (less than or equal to 3.5 hours) after the onset of focal cerebral ischemia in this model.

[1]  G. Press,et al.  Tissue plasminogen activator‐mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits , 1989, Neurology.

[2]  W. Feinberg,et al.  Hemostatic markers in acute stroke. , 1989, Stroke.

[3]  Gregory,et al.  Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. , 1988, Stroke.

[4]  Z. Zakov,et al.  The Heart and Stroke: Exploring Mutual Cerebrovascular and Cardiovascular Issues , 1988 .

[5]  A. Yamadori,et al.  Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. , 1988, Stroke.

[6]  P. Lyden,et al.  Tissue Plasminogen Activator: Reduction of Neurologic Damage After Experimental Embolic Stroke , 1988 .

[7]  W. Hacke,et al.  Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study. , 1988, Stroke.

[8]  I. Koc,et al.  [Thrombolysis of cerebral thromboembolism by urokinase in an animal model]. , 1987, Schweizerische medizinische Wochenschrift.

[9]  E. Braunwald,et al.  Update from the Thrombolysis in Myocardial Infarction Trial. , 1987, Journal of the American College of Cardiology.

[10]  E. Topol,et al.  Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke. , 1987, Journal of neurosurgery.

[11]  J. Seibert,et al.  Digital angiographic quantification of blood flow dynamics in embolic stroke treated with tissue-type plasminogen activator. , 1987, Journal of neurosurgery.

[12]  W. Pulsinelli,et al.  Hemorrhagic complications of thrombolytic therapy in experimental stroke. , 1987, Stroke.

[13]  H. Lüders,et al.  The source of 'paradoxical lateralization' of cortical evoked potentials to posterior tibial nerve stimulation , 1987, Neurology.

[14]  C. Fisher,et al.  Observations on Brain Embolism with Special Reference to Hemorrhagic Infarction , 1987 .

[15]  T. Waltz,et al.  Experimental acute thrombotic stroke in baboons. , 1986, Stroke.

[16]  H. Zeumer,et al.  Thrombolytic therapy in stroke: possibilities and hazards. , 1986, Stroke.

[17]  T. Waltz,et al.  The beneficial effect of intracarotid urokinase on acute stroke in a baboon model. , 1986, Stroke.

[18]  D. Collen,et al.  Thrombolytic therapy in the eighties. , 1986, Blood.

[19]  W. Hacke,et al.  Acute vertebral-basilar thrombosis. Angiologic-clinical comparison and therapeutic implications. , 1986, Acta radiologica. Supplementum.

[20]  U. Degirolami,et al.  Tissue plasminogen activator reduces neurological damage after cerebral embolism. , 1985, Science.

[21]  M. Aldrich,et al.  Cerebrovascular complications of streptokinase infusion. , 1985, JAMA.

[22]  W. Heiss,et al.  [Hemorrhagic neurologic complications during therapy with anticoagulants and fibrinolytic agents]. , 2008, Deutsche medizinische Wochenschrift.

[23]  L. Harker,et al.  Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. , 1984, The Journal of clinical investigation.

[24]  W. Hacke,et al.  [Local fibrinolysis in basilar artery thrombosis (author's transl)]. , 2008, Deutsche medizinische Wochenschrift.

[25]  R. Ritz,et al.  Sequential Treatment of Arterial Occlusions with Porcine Plasmin and Low Dose Streptokinase , 1982, Thrombosis and Haemostasis.

[26]  R. Ritz,et al.  Side Effects of Thrombolytic Treatment with Porcine Plasmin and Low Dose Streptokinase , 1982, Thrombosis and Haemostasis.

[27]  C. Korninger,et al.  Studies on the Specific Fibrinolytic Effect of Human Extrinsic (Tissue-Type) Plasminogen Activator in Human Blood and in Various Animal Species in Vitro , 1981, Thrombosis and Haemostasis.

[28]  R. Macko,et al.  Chronic reversible cerebral ischemia: evaluation of a new baboon model. , 1980, Neurosurgery.

[29]  K. Mettinger,et al.  Factor VIII related antigen, antithrombin III, spontaneous platelet aggregation and plasminogen activator in ischemic cerebrovascular disease A study of stroke before 55 , 1979, Journal of the Neurological Sciences.

[30]  J. Garcìa,et al.  Temporary regional cerebral ischemia in the cat. A model of hemorrhagic and subcortical infarction. , 1977, Journal of neuropathology and experimental neurology.

[31]  W. Landau,et al.  Intracranial Bleeding Associated With Urokinase Therapy for Acute Ischemic Hemispheral Stroke , 1976, Stroke.

[32]  Pilgeram Lo.  Abnormalities in clotting and thrombolysis as a risk factor for stroke. , 1974 .

[33]  L. Pilgeram.  Abnormalities in Clotting and Thrombolysis as a Risk Factor for Stroke , 1974, Thrombosis and Haemostasis.

[34]  McKee Pa,et al.  Streptokinase and urokinase activation of human, chimpanzee and baboon plasminogen. , 1971 .

[35]  P. McKee,et al.  Streptokinase and Urokinase Activation of Human, Chimpanzee and Baboon Plasminogen , 1971, Thrombosis and Haemostasis.

[36]  D. Cox,et al.  The analysis of binary data , 1971 .

[37]  D. G. Beech,et al.  Statistical Theory and Methodology in Science and Engineering. , 1961 .

[38]  R. D. Adams.  Observations on brain embolism with special reference to the mechanism of hemorrhagic infarction. , 1950, The Journal of clinical investigation.