Clot Volume Research Articles

Local fibrinolysis and aspiration of intracerebral hematomas in rats. An experimental study using MR monitoring

Serial magnetic resonance (MR) imaging has not yet been validated in the therapy of experimental intracerebral hematomas in a rat model. It is possible to test the effect of local fibrinolysis and aspiration on the clot volume using serial magnetic resonance imaging and different MR-sequences. Experiments were carried out in 22 male Sprague-Dawley rats. Intracerepra I hematoma was produced by injection of fresh autologous blood into the caudate nucleus using a double injection technique. Thirty minutes later 70 rats were treated by injecting 12 µl of recombinant tissue plasminogen activator. MR-imaging was performed immediately after generation of the hematoma and after clot lysis. The clot volume measured in the magnetic resonance images was compared with that obtained in stained histological serial sections at the end of the experiment. Serial MR scanning demonstrated a significant reduction (p<0.07) of hematoma volume after fibrinolysis followed by aspiration of the blood clot. The best correlation between MR- and histological volumetry was found on RF-spoiled FLASH 2D-images. This study documents the efficacy of MRI in detecting and delineating the size of acute intracerebral hematomas and its time course. Local fibrinolysis and aspiration can be simulated in an experimental rat model. [Neural Res 1998; 20: 349-352]

Early protective effects of Iloprost after experimental spinal cord injury

Serial magnetic resonance (MR) imaging has not yet been validated in the therapy of experimental intracerebral hematomas in a rat model. It is possible to test the effect of local fibrinolysis and aspiration on the clot volume using serial magnetic resonance imaging and different MR-sequences. Experiments were carried out in 22 male Sprague-Dawley rats. Intracerepra I hematoma was produced by injection of fresh autologous blood into the caudate nucleus using a double injection technique. Thirty minutes later 70 rats were treated by injecting 12 µl of recombinant tissue plasminogen activator. MR-imaging was performed immediately after generation of the hematoma and after clot lysis. The clot volume measured in the magnetic resonance images was compared with that obtained in stained histological serial sections at the end of the experiment. Serial MR scanning demonstrated a significant reduction (p<0.07) of hematoma volume after fibrinolysis followed by aspiration of the blood clot. The best correlation between MR- and histological volumetry was found on RF-spoiled FLASH 2D-images. This study documents the efficacy of MRI in detecting and delineating the size of acute intracerebral hematomas and its time course. Local fibrinolysis and aspiration can be simulated in an experimental rat model. [Neural Res 1998; 20: 349-352]

Postoperative subarachnoid clots and the pattern of cerebral ischemia associated with symptomatic vasospasm

We retrospectively evaluated the presence of subarachnoid clots and the development of symptomatic vasospasm in 125 patients who had early surgical treatment of a ruptured cerebral aneurysm. We studied 16 patients (aged 35-86 years; mean, 58.7 years) who underwent surgery 0 to 6 days (mean, 2.1 days) and then manifested symptomatic vasospasm on day 5-12 (mean, day 7.4), and 57 patients (aged 13-79 years; mean, 52.0 years) who underwent surgery 0-8 (mean, day 2.9) and did not manifest symptomatic vasospasm. The volume and location of subarachnoid clots were evaluated with computed tomographic (CT) scanning. Cerebral ischemia was evaluated clinically and also in eight patients, by measurement of cerebral blood flow (CBF) using xenon-enhanced CT. Angiographic evaluation was performed only on one patient. Of the 16 patients with symptomatic vasospasm, the subarachnoid clots were localized, distributed thickly, or associated with intracerebral hematomas in 15 and thin in 1 at the time of admission. Fifteen patients had CT evidence of a subarachnoid clot during vasospasm. Most of the clots were near the ruptured aneurysms, but in three cases, clots were located in the remote cisterns, which were not accessible operatively. The clinical manifestations of vasospasm in these three patients correlated with the site of the clot. CBF was reduced in the territory of the involved artery in all eight patients in whom it was measured. In two of the eight cases, the reduction occurred in the territory of a contralateral artery. In contrast, in the 57 patients without symptomatic vasospasm, the subarachnoid clots were already gone or disappeared soon after surgery in most patients. The continued presence of subarachnoid clots is an important risk factor for symptomatic vasospasm after the rupture of a cerebral aneurysm. The clot is not always located near the ruptured aneurysm, and the clinical course may be unpredictable.

Ventricular dilatation in experimental intraventricular hemorrhage in pigs. Characterization of cerebrospinal fluid dynamics and the effects of fibrinolytic treatment.

Hemorrhagic ventricular dilatation (HVD) is a prominent feature of human intraventricular hemorrhage (IVH) and a strong indicator for poor outcome. We developed an IVH model to define the mechanisms responsible for HVD and to test the efficacy of intraventricular administration of tissue plasminogen activator (TPA) in the treatment of HVD. Isolated IVH was produced in pigs by injecting 10 mL of blood simultaneously with thrombin into the right lateral ventricle. The treatment group received 1.5 mg of TPA after induction of IVH. Intraventricular blood volume and the volume of the lateral ventricles were assessed by CT after 90 minutes, 7 days, and 42 days. Intracranial pressure, the pressure-volume index, and the resistance to outflow of cerebrospinal fluid (R(out)) were measured 30 minutes and 7 days after IVH. After IVH, the volume of the lateral ventricles increased from 1.98 +/- 0.69 to 6.43 +/- 1.23 mL (P < .001). There was a linear relationship between ventricular and clot volume (P = .014). Initially, R(out) increased from 24.34 +/- 7.13 to 63.56 +/- 64.91 mm Hg/mL per minute (P < .001). After 7 days, restoration of normal cerebrospinal fluid circulation occurred, but the ventricles were still significantly enlarged (5.24 +/- 1.76 mL, P < .001) and filled with blood. Within 6 weeks, ventricular volume had returned to normal values, paralleled by complete clot resolution. Intraventricular administration of TPA significantly accelerated clot clearance and restoration of normal ventricle volume. These results suggest that intraventricular bleeding may cause impairment of cerebrospinal fluid circulation but that the mass effect of clots distending the ventricle walls is the most important mechanism responsible for HVD. This model closely imitates several prominent features of human IVH and may therefore be a useful tool for preclinical assessment of the efficacy and safety of treatment with TPA.

Thrombelastographic evaluation of coagulation in transurethral prostatectomy.

To assess the changes in overall coagulation status and define the degree of systemic fibrinolysis occurring in patients undergoing transurethral prostatectomy (TURP). Thirty patients undergoing TURP, 23 for benign prostatic hyperplasia and seven for prostatic carcinoma, were studied prospectively. Serial venous blood samples were taken using the two-syringe technique. Samples were taken before, during and at intervals up to 72 h and 10-14 days after surgery. Thrombelastography (TEG) was performed on native whole blood samples. Peri-operative blood loss was assessed, until the catheter was removed, by photometric estimation of the haemoglobin content of the irrigant fluid and the measurement of clot volume. There was no evidence of fibrinolysis (TEG Percentage Clot Lysis Ly60 > 15%) in any patient over the whole peri-operative period. There was a significant change in the mean TEG variables towards hypercoagulation from 3 h until 10-14 days postoperatively, compared with the pre-operative values (P < 0.05). There was a significant correlation between blood loss and clot volume. These results question the role of systemic fibrinolysis in primary and secondary haemorrhage following TURP and thus the rationale of using antifibrinolytics in these patients. The persistent hypercoagulable state post-operatively indicates a possible role of hypercoagulability in clot retention.

Experimental intracerebral hemorrhage: description of a double injection model in rats.

For experimental purposes, the most common technique of producing an intracerebral hematoma in rats is the injection of unclotted autologous blood. All modifications of this model share the problem that size and extension of the hematoma are not reproducible, because the injected blood either ruptures into the ventricular system or it extends to the subarachnoid or subdural space. Therefore a double injection model of experimental intracerebral hemorrhage in rats has been developed using 19 male Sprague-Dawley rats. After inducing anesthesia a cannula was stereotactically placed into the caudate nucleus and an intracerebral hematoma was produced with the double injection method in which first a small amount of fresh autologous blood is injected which is allowed to clot (preclotting) in order to block the way back along the needle track; the actual hematoma is produced in a second step of the injection. The clot volume was measured on stained serial sections. A total injection volume of 50 microliters of autologous blood produced intracerebral hematomas of 41.1 +/- 10.0 microliters and of similar shapes. The double injection method allows to generate reproducible hematomas in rats. This new model of intracerebral hemorrhage will allow further investigation of fibrinolytic and cytoprotective therapies.

Why Not 100% Equities

Abstract Objective To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). Design Cohort study with logistic regression analysis to combine predictors and treatment modality. Setting Subarachnoid Haemorrhage International Trialists’ (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. Participants Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models. Main outcome measure Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale. Results Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a “neuroimaging model,” with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort. Conclusion The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

Radiological and clinical criteria for the management of epidural hematomas in children.

Modern neuroimaging and intensive care permit precise delineation and specific treatment of head injury. Children sustaining cranial trauma associated with epidural hematoma (EDH) represent a heterogeneous group with a variety of clinical outcomes. Treatment consists of simple observation or surgical evacuation. We attempted to define radiological characteristics of the EDH patients that underwent surgical evacuation. We reviewed the records and computed tomography scans of 33 children sustaining cranial trauma associated with EDH treated at the Children's National Medical Center between October 1990 and August 1994. The radiological and clinical characteristics of children treated surgically (n = 13) and nonsurgically (n = 20) were compared. Mass effect, a temporal clot location, thickness, length and volume of the clot, and midline shift (p < 0.05) differed significantly between groups. The most important radiological parameters in determining the therapeutic intervention were thickness, midline shift, mass effect, and EDH location. A thickness of the EDH > 18 mm, a midline shift >4 mm, and moderate or severe mass effect correctly predicted therapy in 29 out of 33 patients. By adding the location as a fourth parameter, therapy was accuratly predicted in 31 of 33 patients. Mechanism of injury, interval from injury to initial computed tomography scan, age, sex, Glasgow coma score on admission, or lengths of hospital and intensive care unit stays were not significantly different between groups. Although radiological criteria predict surgical intervention for larger EDH, patients harboring intermediate-size EDH will continue to require careful individualized clinical judgement.

Study of thrombus from thrombosed hemodialysis access grafts.

To determine the volume and composition of clot within thrombosed hemodialysis access grafts. Clots were collected in 22 patients at surgical thrombectomy of polytetrafluoroethylene grafts. Histologic analysis was performed in 10 of these clots plus 21 randomly selected clots from the pathology archives. A small, firm piece of whitish thrombus ("arterial plug") was almost always recovered from the arterial limb of the graft. This plug had a concave surface and ranged from 5 mm to 3 cm in length. The remaining clot was soft, red thrombus. The mean weight of all clots was 3.4 g, and mean volume was 3.2 cm3. Average graft length was 42 cm. Histologically, the arterial plug had a characteristic appearance of densely compacted alternating layers of erythrocytes and fibrin. Clot volume in thrombosed dialysis grafts is much less (approximately equal to 25%) than would be expected if the graft were completely filled with thrombus, a finding of significance to mechanical thrombolytic techniques. Resistance of the arterial plug to pulse-spray thrombolysis is likely due to compaction.

Fibrin structure and concentration alter clot elastic modulus but do not alter platelet mediated force development

During clot retraction, platelets interact with fibrin resulting in marked reduction of clot volume. Altered fibrin structure has been reported to affect clot retraction as measured by serum expression. This study was performed to test whether such altered retraction was the result of increased resistance to network collapse or due to decreased force development by platelets. Altered fibrin structure was documented as variation of fibre mass/length ratios (mu) and shifts in clot elastic modulus. The force developed by platelets during clotting was measured directly. Increasing the fibrinogen concentration led to thinner fibre formation (decreased mu), and a linear increase in gel elastic modulus. Over a fibrinogen concentration range of 100 to 400 mg/dl, force development was minimally affected. Force development and clot elastic modulus increased in a linear fashion with increasing platelet concentration. Increasing the calcium concentration from 5 to 20 mM caused a 160% increase in fibrin fibre size (mu), and a 52% decline in clot modulus. Force developed at 1200 s declined by 17%. At 15 mg/ml, dextran and hydroxyethyl starch (HES) also increased mu, and decreased clot modulus; however, both agents markedly reduced force development. Increasing ionic strength or the addition of IgG decreased mu and increased gel elastic modulus. Force development increased modestly with increased ionic strength, did not change with addition of IgG in saline and declined with addition of IgG in maltose. This study indicates that force development is primarily dependent on platelet function while clot modulus depends on both fibrin structure and platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)

Filling a Dialysis Circuit with Albumin Does Not Prevent Platelet Activation During Hemodialysis: In Vivo Study

The aim of our prospective clinical study was to evaluate whether filling a dialysis circuit with albumin before hemodialysis (HD) can prevent platelet activation during the procedure. Eight patients with chronic HD participated in the study, each dialyzed first with albumin and a week later without it. All other parameters of the HD procedure were unchanged (cellulose acetate hollow fiber dialyzer, blood flow of 300 ml/min, and low dose heparin). Before HD with albumin, 6.7% human albumin in saline was recirculated in the dialysis circuit for 10 min at a flow rate of 100 ml/min, and infused into the patient. We found a significant increase in the beta-thromboglobulin levels during both procedures. We found no difference in plasma coagulation system activation measured by fibrinopeptide A concentration. Neither was there any difference in the macroscopic antithrombotic activity assessed at the end of HD by measuring the volume of clots in the arterial and venous bubble trap and by counting the number of clotted fibers in the dialyzer. It seemed that filling the dialysis circuit, which had a cellulose acetate dialyzer, with human albumin did not improve its thrombogenicity.

Stereotactically guided thrombolysis of deep cerebral hemorrhage: preliminary results.

The neurologic outcome from conventional medical or surgical therapy of intracerebral hemorrhage (ICH) is poor; however, stereotactically guided instillation of thrombolytic agents to dissolve parenchymal clots due to hypertensive hemorrhage has recently produced results equal to or better than those obtained with conventional therapies. To determine whether stereotactic thrombolysis of deep ICH is safe and effective. We administered urokinase to clots in four patients with hypertensive ICH. After the hemorrhage was localized using angiography and computed tomography-assisted stereotactic technique, a ventricular catheter was used to administer urokinase to the clot. Preliminary results showed dramatic reduction in clot volume within 48 hours of initiating treatment and modest clinical improvement in all four patients. No further hemorrhages were seen after treatment. Three patients ultimately died of non-neurologic causes. With careful patient selection, stereotaxy-assisted thrombolytic therapy may be an advance in the treatment of certain cases of ICH.

Effects of intrathrombic administration of prostaglandin E1 during pulse-spray thrombolysis with tissue-type plasminogen activator in experimental thrombosis.

The effects of intrathrombic and intravenous injection of prostaglandin E1 (PGE1) during pulse-spray thrombolysis were studied in a rabbit model. Thrombi were produced in the inferior vena cava of 46 rabbits by means of vessel wall injury and placement of steel coils. At 2 days, pulse-spray thrombolysis was performed by using a catheter with multiple side holes spanning the clot. A control group received injections of saline. In all other rabbits, 3 mg of tissue-type plasminogen activator (tPA) was injected into the thrombus over 1 hour, and 500 U of heparin was intravenously administered. PGE1 was administered either intravenously (50 micrograms) or directly into the thrombus (10, 25, or 50 micrograms) in four groups. After treatment, the rabbits were killed and the residual clot was weighed. The relationship between clot length and volume measured on angiograms and clot weight was assessed in 13 additional untreated rabbits. Linear regression analysis was used to estimate the initial clot weight on the basis of measured clot length in treated animals. The extent of clot lysis was significantly greater with injection of tPA and 10-, 25-, or 50-micrograms PGE1 directly into the thrombous than with administration of tPA alone.

The Use of Tissue Plasminogen Activator to Declot Arteriovenous Accesses in Hemodialysis Patients

Thrombosis is the most common complication of arteriovenous (A-V) access, resulting in malfunction or total failure. We describe the first use of the thrombolytic agent tissue plasminogen activator (t-PA) to declot the A-V access in 15 hemodialysis patients (14 A-V grafts and one fistula). The t-PA was infused directly into the A-V access in 10-mg doses, at 2-hour intervals, to a maximum of 30 mg. As determined by angiography, t-PA infusion resulted in a dramatic decrease in clot volume in all cases and complete lysis, with return of bruit and thrill, in 10 patients. Eight of the 10 were able to be treated with hemodialysis via the A-V access the following day. In these patients, angiography demonstrated stenosis at the venous end of the A-V access in eight of nine A-V grafts (the one fistula did not have a venous stenosis). Three patients reclotted within 24 hours, and one had bleeding 5 days later after dialysis requiring compression of the A-V access, which resulted in reclotting. Five patients had functioning A-V grafts 1 to 15 months after t-PA treatment (with angioplasty of the venous stenosis required in three of these), and one patient was lost to follow-up. All five patients in whom t-PA infusion was only partially successful had venous stenosis. One patient died before surgery (unrelated to t-PA). Thus, venous stenosis was present in 13 of 15 A-V accesses studied, the highest incidence reported to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of adjunctive intrathrombic heparin with pulse spray thrombolysis in rabbit inferior vena cava thrombosis.

The efficacy and speed of pharmacomechanical thrombolysis may be limited by thrombotic effects of activated platelets and thrombin within the lysing clot. The authors designed an animal model of subacute venous thrombosis which was used to evaluate the effect of intrathrombic versus intravenous heparin during thrombolysis. Inferior vena cava (IVC) thrombosis was induced in rabbits by balloon catheter injury and placement of steel coils. Venacavagrams were obtained 48 hours later to document clot formation and for angiographic estimation of clot volume. Pulse-spray thrombolysis was performed by forceful injections of various agents through a catheter with multiple side holes spanning the clot. Most animals were given aspirin (30 mg orally) before treatment. After 1 hour of therapy, repeat venacavography was performed. Animals were killed, and residual clot weight was determined. Occlusive IVC thrombi were present in 94% of rabbits at 2 days. Mean residual clot weight per milliliter of estimated initial clot volume (mg/mL) for the various treatment groups was as follows: saline (n = 5) 632 +/- 54; tissue-type plasminogen activator (t-PA) 3 mg, (n = 6) 443 +/- 162; t-PA 3 mg + heparin 750 U intravenously, (n = 7) 408 +/- 128; t-PA 3 mg + heparin 500 U intrathrombic + heparin 250 U intravenously, (n = 8) 213 +/- 166. Differences among these groups (except t-PA alone versus t-PA + intravenous heparin) were significant. The extent of lysis with intrathrombic + intravenous heparin was not significantly retarded by withholding aspirin (n = 6, 194 +/- 72), or improved by giving half the intrathrombic heparin before t-PA injections (n = 6, 280 +/- 158). The results demonstrate the advantage of adjunctive intrathrombic + intravenous heparin over intravenous heparin alone in increasing the extent of pulse-spray thrombolysis in this IVC thrombosis model.

Computerized Tomography and Clinical Features of Large Cerebral Hemorrhages

We studied 17 consecutive patients with nonaneurysmal cerebral hemorrhages larger than 55 cm³ to determine the computerized tomographic correlates of stupor and coma. Coma was associated with 8 mm or greater pineal displacement in 8 of 14 comatose patients. An extension of the clot that occupied or displaced the lower diencephalic region explained coma in the remaining 6 patients with less than 8 mm horizontal pineal displacement. All patients with diencephalic clot were comatose. Three initially drowsy or stuporous patients had 3 mm mean pineal displacement. Massive hydrocephalus occurred in 5 patients, always associated with diencephalic clot, and therefore never independently accounting for coma. Clot volume could be estimated from: volume (cm³) = [largest clot diameter (cm) X 14] – 14. We incidentally found that at least 6 of the 17 massive hemorrhages had progressed from smaller clots.

Vertex Epidural Hematomas

Abstract Four cases of vertex epidural hematomas are presented to illustrate the unique management problems which set them apart from their more common counterparts located over the temporal convexity. Diagnosis requires a high degree of suspicion as vertex epidural hematomas are often missed by conventional horizontal scanning. Coronal computed tomographic scanning should be undertaken in all suspected cases. Clinical symptoms exceeding the small volume of clot may be present due to venous obstruction and disruption of cerebrospinal fluid absorption. Evacuation of the clot usually leads to clinical improvement.

Biphasic ventricular dilatation following posterior fossa subdural hematoma in the full-term neonate.

Five full-term neonates with a posterior fossa subdural hematoma caused by birth injury are reported. All of the patients were successfully treated with surgery. They all presented with biphasic ventricular dilatation as demonstrated by serial computerized tomography (CT) scanning. The initial dilatation due to obstructive hydrocephalus disappeared after removal of the hematoma; however, a second dilatation without obstruction of the ventricular system developed between 2 and 4 weeks after surgery. A ventriculoperitoneal shunt was required in one case because of progressive enlargement of the head size in the chronic stage. The other four patients showed transient dilatation of the ventricles without symptoms of increased intracranial pressure. Subarachnoid hemorrhage associated with posterior fossa subdural hematoma is considered to be the most likely causative factor for the delayed ventricular dilatation. The degree of dilatation roughly depended on the volume of the subarachnoid clot that was demonstrated on the initial CT scan.

Effect of clot removal at 24 hours on chronic vasospasm after SAH in the primate model.

The efficacy of complete clot removal 24 hours after subarachnoid hemorrhage (SAH) in the prevention of chronic cerebral vasospasm was evaluated in monkeys in a blind randomized controlled trial. Twenty-four monkeys were randomized to one of three groups to undergo sham-operation (sham-operated group), clot placement only (clot group), or clot placement and removal (clot-removal group). By means of standard microsurgical techniques, the major cerebral vessels bilaterally were dissected free of arachnoid. An autologous hematoma averaging 5 gm was placed around the vessels in the subarachnoid spaces in the clot and clot-removal groups. Saline solution was instilled in the subarachnoid spaces of the sham-operated group. All animals underwent reoperation 24 hours after the first procedure. In the clot-removal group, the hematoma was evacuated. In the sham-operated and clot groups, the incision was simply closed again after 3 hours of anesthesia. Indices monitored before and 7 days after SAH induction included neurological status, angiographic cerebral vessel caliber, and arterial blood pressure. All animals were evaluated with magnetic resonance imaging (MRI); representative animals were evaluated with computerized tomography (CT) brain scans. There were no neurological deficits in either the sham-operated or the clot-removal groups. One animal in the clot group developed a progressive delayed ischemic deficit on Day 5 after SAH. A second animal in this group died suddenly on Day 4 post-SAH. An autopsy revealed a recent infarct in the territory of the superior cerebellar artery. Clinical findings correlated with MRI and CT images. Significant vasospasm (25% to 100% reduction in vessel caliber) was present on Day 7 in 100% of the clot animals (p less than 0.01). There was no significant vasospasm (p greater than 0.05) on Day 7 in either the sham-operated or the clot-removal groups. A large volume of clot placed bilaterally resulted in a 25% incidence of delayed ischemic deficit. Evacuation of subarachnoid hematoma within 24 hours of SAH prevented the development of chronic vasospasm and delayed ischemic deficit in the primate model.

Lysis of intraventricular blood clot with urokinase in a canine model

Nine millilitres of preclotted autologous blood was injected into the ventricles of 10 adult mongrel dogs (control dogs) to create subtotal ventricular casts with solid clots. The neurological status and systemic fibrinolytic profiles were closely monitored, and the changes in clot and ventricular volumes were measured by serial computed tomography (CT) for 3 months. The control animals showed severe neurological impairment for 7 to 9 days. No visible lysis of the intraventricular clots occurred for 5 to 7 days, after which slow clot lysis occurred at a constant rate. Complete lysis of the 10 clots took 38 to 65 days, indicating that canine cerebrospinal fluid normally possessed limited capacity for in situ fibrinolysis. Of the 10 control dogs, 8 developed progressive ventricular enlargement after a transient initial shrinkage parallel with initial clot lysis. Their final ventricular volume at 3 months was as much as 14 times the base line ventricular volume. Necropsy studies disclosed increased basal subarachnoid fibrosis and extensive ependymal and subependymal damage in the lateral ventricular walls of the hydrocephalic dogs. Ten other dogs (UK dogs) were given similar ventricular clot injections. Six hours later, each UK dog was begun on a regimen of 20,000 IU of intraventricular urokinase every 12 hours until solid clots were no longer seen in the ventricles on CT. In all 10 UK dogs, intraventricular urokinase induced complete lysis in 3 to 6 days without causing local or systemic hemorrhages. The neurological status of all 10 dogs also improved promptly. In 8 UK dogs, the ventricles that were initially distended by clots showed rapid shrinkage parallel with thrombolysis to a final volume at 3 months of less than four times the initial ventricular volume. Only 2 animals had persistently large or expanding ventricles. At necropsy, the ependymal and subarachnoid spaces of the UK dogs were remarkably free of damage and fibrosis. The possible mechanisms by which intraventricular urokinase may prevent posthemorrhagic hydrocephalus are discussed. (Neurosurgery 19:553-572, 1986)