Intracisternal recombinant tissue plasminogen activator after aneurysmal subarachnoid hemorrhage

1991 ◽  
Vol 75 (2) ◽  
pp. 181-188 ◽  
Author(s):  
J. Max Findlay ◽  
Bryce K. A. Weir ◽  
Neal F. Kassell ◽  
Lew B. Disney ◽  
Michael G. A. Grace
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Aneurysm Rupture ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Acceptable Risks ◽  
Tissue Plasminogen ◽  
Fine Print

✓ Fifteen patients undergoing surgery within 48 hours of aneurysm rupture were administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after minimal surgical clot removal and aneurysm clipping. Preoperatively, 13 patients had diffuse or localized thick subarachnoid blood clots on computerized tomography (CT), and two had diffuse thin clots. The rt-PA was given as a single intraoperative injection of 7.5 mg (one patient), 10 mg (nine patients), or 15 mg (five patients). Postoperative cisternal drainage was employed in three patients. All patients except one demonstrated partial to complete cisternal clot clearance on CT scans within 24 hours after surgery. The patient who showed no clot reduction was the only patient in this series to develop symptomatic vasospasm and was the only fatality, dying 8 days after rupture. No vasospasm was seen on follow-up cerebral angiography in six of the 14 responding patients, and mild-to-moderate arterial narrowing was seen in at least one major cerebral artery in the remaining eight patients. Severe angiographic vasospasm was not seen, although the patient who died did not undergo repeat angiography. There was one major complication early in the series which seemed clearly related to treatment, and that was a large extradural hematoma occurring within several hours of craniotomy. Intrathecal fibrinolytic treatment appears effective in clearing subarachnoid clot and reducing vasospasm, and may be associated with acceptable risks if given to patients with large-volume subarachnoid hemorrhages at high risk for severe vasospasm.

Tissue plasminogen activator thrombolysis of a middle cerebral artery embolus in a patient with an arteriovenous malformation

1991 ◽  
Vol 74 (5) ◽  
pp. 808-812 ◽  
Author(s):  
Jafar J. Jafar ◽  
Walter S. Tan ◽  
Robert M. Crowell
Keyword(s):  
Arteriovenous Malformation ◽  
Middle Cerebral Artery ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cerebral Artery ◽  
Thrombolytic Agent ◽  
Recombinant Tissue Plasminogen Activator ◽  
Content Type ◽  
Tissue Plasminogen ◽  
Fine Print

✓ A patient harboring a cerebral arteriovenous malformation (AVM) underwent angiography in an attempt to embolize the AVM. During catheterization (and prior to embolization) he became hemiplegic and aphasia Angiography revealed a complete middle cerebral artery (MCA) occlusion by an embolus. The patient was treated with recombinant tissue plasminogen activator (t-PA), a thrombolytic agent. Restoration of MCA flow was achieved, and the patient recovered. Immediately after MCA embolus, t-PA infusion may lead to thrombolysis and neurological recovery. The decision-making process as well as the risks associated with the use of t-PA are discussed.

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

2002 ◽  
Vol 97 (4) ◽  
pp. 954-962 ◽  
Author(s):  
Veit Rohde ◽  
Ina Rohde ◽  
Ruth Thiex ◽  
Azize Ince ◽  
Axel Jung ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Treated Group ◽  
Fibrinolytic Therapy ◽  
Untreated Group ◽  
Hematoma Volume ◽  
Edema Formation ◽  
Content Type ◽  
Tissue Plasminogen ◽  
Fine Print

Object. 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.

Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection

1999 ◽  
Vol 90 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Kenneth R. Wagner ◽  
Guohua Xi ◽  
Ya Hua ◽  
Mario Zuccarello ◽  
Gabrielle M. de Courten-Myers ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Mass Effect ◽  
Content Type ◽  
Tissue Plasminogen ◽  
Clot Aspiration ◽  
Perihematomal Edema ◽  
Fine Print

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.

Lysis of intraventricular hematoma with tissue plasminogen activator

1991 ◽  
Vol 74 (5) ◽  
pp. 803-807 ◽  
Author(s):  
J. Max Findlay ◽  
Bryce K. A. Weir ◽  
Dan E. Stollery
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Blood Clot ◽  
Artery Aneurysm ◽  
Recombinant Tissue Plasminogen Activator ◽  
External Ventricular Drainage ◽  
World Federation ◽  
Content Type ◽  
Tissue Plasminogen ◽  
Cerebral Artery Aneurysm

✓ A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home.

Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

1988 ◽  
Vol 60 (01) ◽  
pp. 107-112 ◽  
Author(s):  
Roy Harris ◽  
Louis Garcia Frade ◽  
Lesley J Creighton ◽  
Paul S Gascoine ◽  
Maher M Alexandroni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Half Life ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rat Plasma ◽  
High Molecular Weight Complex ◽  
Molecular Weights ◽  
Major Activity ◽  
Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

Sign in / Sign up

Export Citation Format

Share Document