Coagulative and Fibrinolytic Activation in Cerebrospinal Fluid and Plasma after Subarachnoid Hemorrhage

Ikeda, Keisuke; Asakura, Hitoshi; Futami, Kazuya; Yamashita, Junkoh

doi:10.1097/00006123-199708000-00002

Cited by 57 publications

(28 citation statements)

References 26 publications

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“…The levels of activated proteases in these systems reportedly elevate in the CSF during the acute phase after SAH, which is considered to be an etiologic factor of cerebral vasospasm. 10,[12][13][14]27 FUT-175 inhibits complement factors thrombin and plasmin and suppresses the protease-based inflammation. 18,19 FUT-175 has been used for disseminated intravascular coagulation in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Zhang

Nagata

Kikuchi

et al. 2001

Stroke

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Background and Purpose-Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade-based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors-FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin-on the development of cerebral vasospasm in a rabbit SAH model. Methods-One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2 days after SAH. Nine groups of rabbits (nϭ6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor-BB (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 g of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours. Results-Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52Ϯ5.0%; 5 mg, 79Ϯ5.7%; 10 mg, 80Ϯ2.5%; 20 mg, 80Ϯ3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52Ϯ6.4%; 2.5 mg, 81Ϯ9.0%; 5 mg, 85Ϯ4.1%) (PϽ0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries. Conclusions-Activation

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Section: Discussionmentioning

confidence: 99%

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Zhang

Nagata

Kikuchi

et al. 2001

Stroke

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“…11) However, little data on tPA and plasminogen activator inhibitor-1 activities in CSF after SAH are available. 7,17) The hypothesis of the present investigation was that washout of extrinsic tPA does not depend on the initial dose, but on the individual patient conditions, such as anatomical variations of the cisterns, extent of surgical opening of the cistern walls, and J. Jito et al…”

Section: Introductionmentioning

confidence: 78%

“…Third, the plasminogen activator inhibitor-1 level is significantly high in the CSF and plasma of patients with severe SAH. 7) Therefore, a treatment strategy to remove clots effectively from the cisterns and ventricles requires adequate amounts of extrinsic thrombolytic factors to be given directly to the clots in the CSF space.…”

Section: Discussionmentioning

confidence: 99%

Tissue Plasminogen Activator Levels After Single Intracisternal Injection in Patients With Subarachnoid Hemorrhage

Jito

Nakasu

et al. 2004

Neurol. Med. Chir.(Tokyo)

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Tissue plasminogen activator (tPA) levels were investigated in the cisternal fluid of patients with subarachnoid hemorrhage treated with single intracisternal injection of recombinant tPA during radical surgery for ruptured aneurysms. Seven patients received different doses of tPA: two of 400 mg/ml, three of 500 mg/ml, one of 700 mg/ml, and one of 800 mg/ml in a total amount of 20 ml distilled water at pH 7. Cerebrospinal fluid samples were taken directly from the cisternal fluid at 15-minute incubation after injection, immediately after irrigation during surgery, and by lumbar tap 2 days after surgery. Cisternal tPA levels decreased to about 60% of the mean injected doses after 15-minute incubation. Simple linear regression analysis showed these tPA levels after incubation correlated with the initial doses. After copious irrigation with Ringer solution at pH 8, tPA levels decreased rapidly without correlation with the initial doses. After spinal drainage for 2 days, tPA levels further decreased by an order of 10 -4 to 10 -6 from the initial dose. These values were still greater than normal controls. The final values of tPA levels were not related to the initial dose. None of the patients suffered from systemic or wound complications. Cisternal tPA injection with increased doses and irrigation may be beneficial for the selective rapid removal of blood clots with controllable safety.

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“…PAI-1 was also the highest in the 120-IU/mL group, and it gradually decreased during the irrigation period. Ikeda et al 20 reported that patients whose PAI-1 levels in CSF were Ͼ20 ng/mL had a high incidence of vasospasm and a poor outcome. However, the fact that TAT and PAI-1 were highest in the 120-IU/mL group in the present study suggested that these results were due to clot lysis or clot volume.…”

Section: Discussionmentioning

confidence: 99%

Urokinase Cisternal Irrigation Therapy for Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Sasaki

Kodama

Kawakami

et al. 2000

Stroke

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Background and Purpose-Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated. Methods-This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher's group 3, CT number [Hounsfield units] Ͼ60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or chiasmatic cistern (outlet). Lactated Ringer's solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system. Results-Symptomatic vasospasm was observed transiently in 3 cases (10.7%) without any low-density area on CT scan.In the 120-IU/mL group, no symptomatic vasospasm occurred. Analysis of drainage fluid suggested that UK 120 IU/mL is effective. The mean values of total drained blood volume for the respective groups were as follows: 58 mL in 30 IU/mL, 106 mL in 60 IU/mL, and 143 mL in 120 IU/mL. No abnormal changes were observed in the coagulative and fibrinolytic systems after UK irrigation. Conclusions-These results suggest that cisternal irrigation therapy with UK is safe and effective for the prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. (Stroke. 2000;31:1256-1262.)

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Coagulative and Fibrinolytic Activation in Cerebrospinal Fluid and Plasma after Subarachnoid Hemorrhage

Cited by 57 publications

References 26 publications

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Tissue Plasminogen Activator Levels After Single Intracisternal Injection in Patients With Subarachnoid Hemorrhage

Urokinase Cisternal Irrigation Therapy for Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage

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