Prospective study on the prevention of cerebral vasospasm by intrathecal fibrinolytic therapy with tissue-type plasminogen activator

1993 ◽  
Vol 78 (3) ◽  
pp. 430-437 ◽  
Author(s):  
Kazuo Mizoi ◽  
Takashi Yoshimoto ◽  
Akira Takahashi ◽  
Satoru Fujiwara ◽  
Keiji Koshu ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Cerebral Vasospasm ◽  
Therapy Group ◽  
Intrathecal Injection ◽  
Neurological Deficits ◽  
Tissue Type ◽  
Control Group ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Cisternal Drainage

✓ The authors have evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in patients with a diffuse thick subarachnoid hemorrhage (SAH). The present study examined 105 patients who underwent direct surgery within 48 hours of SAH and whose computerized tomography (CT) findings were classified as Fisher CT Group 3. Patients showing diffuse thick subarachnoid blood clots on CT with greater than 75 Hounsfield units (HU) were included in the tPA therapy group and those with below 75 HU comprised the control group. The surgical method was the same in both groups, and both groups had cisternal drainage instituted. On the day following the operation, the tPA group was given an intrathecal injection of tPA (2 mg), and this was continued for several days until all of the cisterns exhibited low density on CT scans. Follow-up angiography showed that 26 cases (87%) in the tPA group had no vasospasm, three (10%) had moderate vasospasm, and one (3%) had severe vasospasm. All four patients showing spasm on angiography were asymptomatic, and there were no cases of delayed ischemic neurological deficits (DIND). In contrast, there were 11 cases (15%) with DIND in the control group. In the tPA group, there was one case of SAH caused by drainage catheter removal, one with a small epidural hematoma, and one with subgaleal fluid accumulation; all of these were treated conservatively with favorable results. Overall, there were no infectious complications related to cisternal drainage and intrathecal injection of tPA. These results indicate that multiple intrathecal injections of small doses of tPA are effective and safe in preventing vasospasm. On the basis of this experience, the authors conclude that injection of 2 mg of tPA daily for 5 days (a total of 10 mg) is effective in preventing the development of vasospasm.

Prevention of Vasospasm by Clot Removal and Intrathecal Bolus Injection of Tissue-Type Plasminogen Activator: Preliminary Report

Neurosurgery ◽  
1991 ◽  
Vol 28 (6) ◽  
pp. 807-813 ◽  
Author(s):  
Kazuo Mizoi ◽  
Takashi Yoshimoto ◽  
Satoru Fujiwara ◽  
Takayuki Sugawara ◽  
Akira Takahashi ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Bolus Injection ◽  
Single Photon ◽  
Photon Emission ◽  
Neurological Deficits ◽  
Tissue Type ◽  
Emission Computed Tomography ◽  
Ct Number ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Abstract In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm.

The Changes of Tissue-Type Plasminogen Activator and Matrix Metalloproteinases in Neonatal Mice with Hypoxic-Ischemic Encephalopathy

2012 ◽  
Vol 195-196 ◽  
pp. 447-451
Author(s):  
Jian Wen Xu ◽  
Wei Wang ◽  
Xiao Zhen Zhao ◽  
Geng Zhang ◽  
Juan Bing Wei
Keyword(s):  
Matrix Metalloproteinases ◽  
Basement Membrane ◽  
Plasminogen Activator ◽  
Hypoxic Ischemic Encephalopathy ◽  
Tissue Type ◽  
Control Group ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Hypoxia Ischemia ◽  
Ischemic Encephalopathy

Fetal distress and neonatal asphyxia are key factors which result in neonatal hypoxic-ischemic encephalopathy (HIE). There is growing evidence that tissue-type plasminogen activator (TPA) and matrix metalloproteinases (MMPs) may be involved in extracellular matrix (ECM) degradation in the central nervous system. In this study, the transmission electron microscope was used to observe the growth and development characteristics of the blood-brain barrier (BBB), follow by the activity of TPA and the expression of MMPs in HIE model were detected. The asphyxia in female mice within the last day of gestation was produced by a delayed cesarean section. The experiment was designed for 1 control group and 2 asphyctic groups (15min and 30min), then the activities of TPA and expression of MMPs were detected separately. The results showed that the BBB was not fully developed in newborns, their brain microvascular endothelial cells were not surrounded with intact basement membrane and only had discontinuous basement membrane-like materials of varying thickness. The activity of TPA and the expression of MMPs of brain increased after hypoxia-ischemia in vivo. Based on these findings we concluded that the basement membrane at the BBB was a weak link in the brain, TPA and MMPs could degrade components of the ECM. So these enzymes increased after hypoxia-ischemia might be able to attack the basement membrane of microvessels, then open the BBB and induce the cerebral edema.

Treatment of acute ischemic brain infarction with the assistance of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator

2007 ◽  
Vol 48 (7) ◽  
pp. 774-780 ◽  
Author(s):  
W. Poncyljusz ◽  
A. Falkowski ◽  
I. Kojder ◽  
E. Cebula ◽  
L. Sagan ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cerebral Infarction ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Control Group ◽  
Nihss Score ◽  
Tissue Type Plasminogen Activator ◽  
Intraarterial Thrombolysis ◽  
Type Plasminogen Activator

Background: Cerebral infarction is usually due to arterial occlusion. Prompt treatment with thrombolytic drugs can restore blood flow and improve recovery from an infarct. Purpose: To evaluate the clinical efficacy and safety of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator (rtPA) in patients with acute middle cerebral artery (MCA) infarctions within 6 hours of the onset of symptoms. Material and Methods: Sixteen patients (10 females and six males) aged from 42 to 61 years, with acute MCA territory infarcts were selected for treatment with local i.a. rtPA up to 6 hours after the onset of symptoms. Patient selection was based on clinical examination, computed tomography (CT), and digital subtraction angiography (DSA). A clinical evaluation was performed before treatment, at the time of discharge, and 90 days post-procedure on the basis of modified Rankin and NIHSS scores. Controls ( n = 16, nine females and seven males) aged from 51 to 70 years were treated only with intravenous anticoagulation using i.v. heparin infusion. The control group was evaluated with multidetector CT (MDCT) angiography performed on entry to the study and at 2–4 hours afterwards. Results: Eight patients (50%) achieved a modified Rankin score of 2 or less as the primary outcome after 90 days follow-up. The secondary clinical outcome at 90-day follow-up was as follows: NIHSS score ⩽1, three (19%) of the patients; NIHSS score ⩾50% decrease, nine (56%) of the patients. A recanalization rate of 75% was achieved in 12 of the 16 treated patients, but only 12.5% in two of the 16 patients in the control group. Intracerebral hemorrhage occurred in two (12.5%) of the patients in the treatment group, but in only one patient (6%) in the control group. There were no deaths in the treated group after thrombolysis up to the time of discharge; however, during the 90-day follow-up, two patients died compared to three patients in the control group (19% vs. 12.5% mortality rate). Conclusion: Patients with cerebral infarction who were treated within 6 hours of onset using intraarterial rtPA thrombolysis had a significantly improved clinical outcome 90 days after the procedure compared to patients treated only with intravenous anticoagulation.

Thrombomodulin Levels during Normal Pregnancy, at Delivery and in the Postpartum: Comparison with Tissue-type Plasminogen Activator and Plasminogen Activator Inhibitor-1

1998 ◽  
Vol 79 (03) ◽  
pp. 554-556 ◽  
Author(s):  
N. Mermillod ◽  
J. Amiral ◽  
G. Reber ◽  
de Moerloose
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Pregnancy ◽  
Tissue Type ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Type Plasminogen Activator ◽  
Soluble Thrombomodulin ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor

SummarySome studies suggest that soluble thrombomodulin (TM) could be used as a marker of preeclampsia or eclampsia. However little is known about the sequential changes of TM during the course of normal pregnancy.Levels of TM were determined in 100 women with uneventful pregnancies. Samples (n = 394) were divided into five study intervals, three during pregnancy, one at delivery and one three days postpartum.As compared with TM levels (median 34.3 ng/ml, range 17.6-61) of a control group of 60 healthy non-pregnant women, TM levels were shown to increase throughout pregnancy, median (and range) values being respectively 38.5 (17.6-72.7) from 11 to 20 weeks, 45.2 (22.6-75.2) from 21 to 30 weeks and 54.3 (25.1-114.5) ng/ml from 31st week to delivery. One hour after delivery TM levels were still elevated and dropped three days postpartum to 40.5 (20.9-79.4) ng/ml. The increase of TM levels was correlated with those of tissue-type plasminogen activator and plasminogen activator inhibitor-1 antigens. The large overlap in TM levels between the study periods seems to preclude a clinical use of TM based on reference values from a control group. Our data suggest that it would be more appropriate to take into account TM baseline values in a given woman to examine her TM increase during pregnancy.

Digital angiographic quantification of blood flow dynamics in embolic stroke treated with tissue-type plasminogen activator

1987 ◽  
Vol 67 (3) ◽  
pp. 399-405 ◽  
Author(s):  
Phillip Kissel ◽  
Bahram Chehrazi ◽  
James A. Seibert ◽  
Franklin C. Wagner
Keyword(s):  
Plasminogen Activator ◽  
Evans Blue ◽  
Autologous Blood ◽  
Neutral Red ◽  
Tissue Type ◽  
Facial Artery ◽  
Control Group ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Red Dye

✓ Computer analysis of digital subtraction angiography (DSA) was utilized to quantify the effectiveness of tissue-type plasminogen activator (TPA) in a rabbit cerebroembolic stroke model. Fourteen animals underwent cannulation of the facial artery and a preembolus angiogram. Autologous blood clots were then injected, and occlusion of the internal carotid artery at the circle of Willis was documented with repeat angiogram. The experimental group received a 1-mg/kg intravenous infusion of TPA via a femoral catheter for 90 minutes. A control group received an equivalent volume of saline. Follow-up angiograms were performed every 15 minutes. The TPA-treated animals showed progressive improvement in flow through previously occluded vessels. Time-density curves of the contrast material over the middle cerebral artery trunk and brain parenchyma were generated. The best integrated curves for the two groups were compared at 30 minutes after occlusion and 90 minutes after treatment. Animals were then observed for 24 hours and their neurological status was documented. Premortem infusion of either Evans blue dye or neutral red dye was performed and the integrity of the blood-brain barrier and tissue perfusion were assessed by video planometry. Significant improvements were noted by DSA, and Evans blue and neutral red dye studies in animals treated with TPA.

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