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K Overgaard

Publications and source records attributed to K Overgaard.

At least 55 records · Page 3Linked to original sources

Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model.

The effect of delayed thrombolysis with recombinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embolized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15-240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56-71% after embolization. Reperfusion induced by thrombolytic therapy was demonstrated by comparing the posttreatment angiography of the pooled five treatment groups to control animals. Thrombolytic therapy significantly reduced the infarct volume and improved the prekill clinical score by up to 2 h of treatment delay, and treatment might have been beneficial even after 4 h delay. Prolonging the delay of treatment increased the infarct volume (p < 0.001, Jonck-heere-Terpstra test). Only a few hemorrhagic complications were observed. Thus, thrombolytic therapy in embolic stroke induced recanalization. The effect on clinical outcome and infarct volume was dependent on delay time.

Animals↗

Effect of hypothermia and delayed thrombolysis in a rat embolic stroke model.

Effect of hypothermia on cerebral infarcts was studied in rats embolized in the right carotid territory. Thirty-four served as normothermic controls receiving saline infusion only. In 16 rats hypothermia of 32 degrees C was induced by cooling with a fan, followed by embolization. The rats were kept hypothermic for the following 3 h before body temperature was raised to 37 degrees C. In 26 rats, treatment with human recombinant tissue plasminogen activator (20 mg/kg i.v. during 45 min), started 2 h after embolization. Finally, 14 rats were treated similarly with hypothermia for 3 h followed by additional rt-PA treatment starting after 2 h. Thrombolytic therapy reduced median infarct volume from 19.5% of affected hemisphere among controls to 4.6% (p = 0.006) in the treated group. Three hours of hypothermia reduced infarct volume to 1.6% (p = 0.0007). Additional rt-PA could not demonstrate further improvement in this experimental setting.

Animals↗

Bone metabolism in premenopausal women with nontoxic goiter and reduced serum thyrotropin levels.

OBJECTIVE: To study whether premenopausal women with nontoxic goiter, but reduced serum TSH as a sign of spontaneous subclinical hyperthyroidism have decreased bone mass or other indications of increased bone turnover. DESIGN AND SUBJECTS: In a cross-sectional study, bone mass measurements were performed in the distal forearm and the lumbar spine in 11 premenopausal women with nontoxic goiter and a stable reduction in serum TSH (median (range) 8 months (6-108 months)), and in 22 matched controls. In a longitudinal study, measurements were repeated every 3 months for a maximum period of 2 years in 9 of the patients (6 completed 9 months, 4 completed 2 years follow-up). RESULTS: Serum TSH in the patients were (median (range)) 0.025 mU/l (< 0.005-0.256 mU/l). Patients had a bone mineral content of the distal forearm and a bone mineral density of the lumbar spine similar to those of controls, medians of controls: 98.4% and 93.8%, respectively. The risk of a type 2 error for over-looking a 10% difference was 2% for the distal forearm and 20% for the spine. TSH correlated negatively with marginal significance (p < 0.10) with markers of bone turnover: plasma osteocalcin, serum alkaline phosphatase, and fasting urinary hydroxyproline corrected for creatinine, although all patients had absolute values of these parameters within normal range. During follow-up bone mass measurements did not tend to decrease, but serum alkaline phosphatase and fasting urinary hydroxyproline showed increasing trends (p < 0.05). CONCLUSIONS: Premenopausal women with nontoxic goiter and reduced serum TSH do not seem to have reduced bone mass but seem to demonstrate signs of increased bone turnover.

Adult↗

Thrombolytic therapy in experimental embolic stroke.

The effect of thrombolytic therapy is well-documented in acute myocardial infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated in small series of patients. The point of thrombolytic therapy is to avoid or reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of reperfusion needs further investigation and documentation. This review describes studies of thrombolysis in embolic stroke using animals embolized by intracarotid injections of blood clots. Vascular occlusion was demonstrated by angiography and measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue-type plasminogen activator was initiated after varying periods of time. Reperfusion, cellular function, and brain damage were examined by angiography and by clinical and pathoanatomical examination. Based mainly on results from our own investigations, the following theses concerning ischemic stroke were made: (a) Cerebral infarction caused by arterial occlusion is due to delayed, incomplete, or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor importance. (b) Early thrombolytic therapy in animal models increases the degree of reperfusion and reduces brain damage, clinical deficits, and mortality. (c) Early arterial reperfusion reduces cerebral infarction and related edema. With early reperfusion, the extent of brain damage correlates to the length of the delay from onset of ischemia. (d) Cerebral stunning is caused by arterial occlusion followed by very early spontaneous or induced reperfusion, as neurons temporarily lose their functional capabilities without dying. (e) Multiple embolic microclots in experimental stroke result in more brain damage than a single macroclot, and with clots the extent of brain damage is dependent on the structural composition and volume of emboli. (f) The ability to recanalization in experimental embolic stroke is related to the amount of red cells in the emboli and inversely related to the volume of emboli and to the fibrin content and density of the clots. (g) Infarct-limiting effects in experimental stroke can be obtained by ischemic neuroprotectants or by hypothermia, either alone or with thrombolytic therapy, which then reduces brain damage further.

Animals↗

[Salmon calcitonin in osteoporosis. The effect of intranasal application on bone mineral content and fracture frequency in postmenopausal women with manifest osteoporotic changes].

The objective was to study the dose-related response of intranasal salmon calcitonin (Salcatonin) on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. A total of 208 healthy women aged 68-72 years, who had a bone mineral content (BMC) of the distal forearm 30% below the mean value for healthy premenopausal women, were examined in a double-blind, placebo-controlled, randomized group comparison study. They were randomized to a two-year daily treatment of either 50 IU, 100 IU, 200 IU Salcatonin or placebo. All received 500 mg calcium daily. In the calcium-(placebo)-treated group the BMC of the spine increased 1%, whereas an increase of 3% was seen in the 200 IU Salcatonin treated group. There was a dose-related response to Salcatonin manifested by an increase in BMC of 1.0%/100 IU. The incidence of new fractures was significantly lower in the women treated with Salcatonin (about one third of that in the non-Salcatonin treated women). In conclusion the results suggest that, compared with calcium alone, Salcatonin given intranasally reduces the rate of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.

Administration, Intranasal↗

[No increase in the prevalence of vertebral fractures among postmenopausal women over a 10-year period].

We examined whether the prevalence of vertebral fracture in otherwise healthy, 70-year-old Danish women had increased over a period of ten years. The population-based, epidemiological study included two age-matched, representative samples of postmenopausal women. Group 1 (1979) consisted of 173 healthy women without secondary causes of osteoporosis, Group 2 (1989) of 387 women. X-rays of the thoraco-lumbar spine were assessed for vertebral fracture by five radiological methods. There was no significant difference between the two groups in the prevalence of vertebral fracture and the 95% confidence intervals overlapped completely in all methods. The prevalence rates varied by method from 35% to 80% but the distribution of fracture types was similar in the two groups. We conclude that the prevalence of vertebral fractures due to postmenopausal osteoporosis has not increased since 1979 in suburban Copenhagen, and that comparison of prevalences requires the same method of radiological assessment.

Aged↗

Human growth hormone and growth hormone releasing hormone: a double-masked, placebo-controlled study of their effects on bone metabolism in elderly women.

We treated 42 postmenopausal women with decreased bone mass for 12 weeks with human growth hormone, growth hormone releasing hormone, or placebo. Bone density and biochemical markers were determined before and during treatment, and 4 weeks after withdrawal. Biochemical markers of bone formation and resorption increased significantly in the group treated with growth hormone, whereas no changes were seen in the other groups. After withdrawal of therapy the bone markers declined without reaching baseline values. Bone density in the forearm, spine and proximal femur was unchanged in all groups. We conclude that treatment with growth hormone stimulates bone metabolism in elderly postmenopausal women with decreased bone mass.

Absorptiometry, Photon↗

Enhancing the efficacy of thrombolysis by AMPA receptor blockade with NBQX in a rat embolic stroke model.

Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor blockade and thrombolytic therapy with human recombinant tissue plasminogen activator (TPA) was tested in a rat embolic stroke model. Sixty-three rats were embolized in the right internal carotid territory with a 200 microliters suspension of microclots formed by alternate moving of 150 microliters whole blood and 50 microliters of thrombin between two interconnected syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were treated with NBQX immediately after embolization. Thirty-one rats were treated with TPA 2 h following embolization, and in 16 of these rats additional NBQX treatments were initiated 90 min following embolization. Hemispheric cerebral blood flow (CBF) was measured by an intraarterial 133Xenon injection method before and after embolization. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volumes were measured. Median CBF was reduced by 70-77% in the affected hemispheres following embolization. Significant recanalization occurred in all groups except those treated with NBQX. TPA-treated rats had significantly better reperfusion compared to controls judged by angiography 3 h following embolization (P = 0.04). NBQX alone and TPA alone caused insignificant reduction in infarct volume but, when combined, total infarct volume was reduced by 77% compared to controls (P = 0.02). Separate measurement of cortical infarct revealed significantly smaller infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuroprotection with NBQX and thrombolysis with rt-PA in rat embolic stroke.

The efficacy of delayed thrombolysis with recombinant tissue plasminogen activator was tested in combination with the ischaemic protecting drug NBQX in an embolic stroke model. In 113 rats the carotid territory was embolized with a fibrin-rich clot formed in polyethylene tube. Hemispheric cerebral blood flow (CBF) was measured by intra-arterial 133Xenon injection method before and after embolization. Two hours after embolization 67 animals were treated with tissue plasminogen activator 20 mg kg-1, 46 control animals with saline. NBQX was given to 53 animals, of which 41 animals also received thrombolytic therapy and 12 were saline controls. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after two days, evaluated neuropathologically, and infarct volume was measured. Embolization caused a 60-78% reduction of median CBF. The comparison of post-treatment angiography of thrombolytic treated animals to controls showed significant (p < 0.01) reperfusion in thrombolytic treated animals, while NBQX alone did not enhance reperfusion. Thrombolytic therapy significantly reduced the total infarct volume from 19.5% to 4.5% of embolized hemisphere volume (p = 0.006). NBQX alone reduced total infarct volume from 19.5% to 6.5% and cortical infarct volume from 7.9% to 0.3% (p = 0.03). In thrombolytic treated animals NBQX reduced total infarct volume from 4.5% to 2.1%. The more than 50% reduction of total infarction volume caused by NBQX was not statistically significant due to the variation of infarct size in this model. Small haemorrhagic lesions in infarcts were observed in thrombolytic treated animals. The clinical outcome correlated well with infarct volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Thrombolytic therapy in acute ischemic stroke. A Danish pilot study.

BACKGROUND AND PURPOSE: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow. METHODS: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms. RESULTS: Angiography 16 to 24 hours after treatment in 17 patients showed patient intracranial arteries in 12, partial occlusion of the middle cerebral artery in 3, and total occlusion of the middle cerebral artery in 2. rCBF with 99mTc-hexamethylpropyleneamine oxime intravenously was measured 5 minutes before and within 24 hours after thrombolytic therapy in 12 patients. 10 of the 12 patients showed brain tissue reperfusion and 2, with angiographically documented middle cerebral artery occlusion, showed no reperfusion, thus documenting a relationship between reperfusion measured by regional cerebral blood flow and angiographic patency (P = .015). Three patients died. Patients who were reperfused within 24 hours (documented by repeated regional cerebral blood flow measurements) showed greater clinical improvement on the Scandinavian Stroke Scale the sooner their thrombolytic therapy was started and the more severe their neurological deficits. CONCLUSIONS: Acute cerebral ischemia can be documented by rCBF measurements without delay of thrombolytic therapy, and repeated rCBF measurements can reveal whether cerebral reperfusion has occurred. In our study, early reperfusion was associated with clinical improvement.

Adult↗

Neuroprotection by excitatory amino acid antagonist augments the benefit of thrombolysis in embolic stroke in rats.

BACKGROUND AND PURPOSE: The effects of delayed thrombolysis with alteplase and neuroprotection with an excitatory amino acid receptor antagonist and their combination were tested in an embolic stroke model. METHODS: In 61 rats the carotid artery territory was embolized with arterial-like fibrin-rich clots. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial 133Xe injection method. The animals were assigned to one of the following treatments: (1) vehicle-treated controls (n = 15); (2) dizocilpine 1 mg/kg i.v. 5 minutes after embolization (n = 16); (3) alteplase 20 mg/kg as an intravenous continuous infusion starting 2 hours after embolization (n = 16); and (4) both agents (n = 14). Carotid angiography displayed the site of occlusion of the cerebral arterial tree immediately after and 3 hours after embolization, and the clinical neurological score was assessed after the rats recovered from anesthesia and before the rats were killed. Brains were fixed after 2 days and evaluated neuropathologically; infarct volume affecting cortical and deep brain structures was measured separately. RESULTS: Both alteplase and dizocilpine reduced the total infarct volume (P = .05 and P = .04, respectively, Mann-Whitney tests). Dizocilpine reduced the incidence of cortical infarctions by 48% (P < .001, Fisher's test). Only the combined treatment significantly reduced deep brain infarctions (P = .03, Mann-Whitney test). The combined treatment also improved the clinical score by 83% compared with controls, by 75% compared with the group treated by dizocilpine alone, and by 50% compared with the group treated by alteplase alone. Sixty-seven percent of thrombolytic-treated animals recanalized completely compared with 39% of those given no thrombolytics (P = .05, Fisher's test). The clinical outcome correlated with infarct size (P < .01, Spearman test). CONCLUSIONS: Our results document comparable efficacy of delayed thrombolysis and excitatory amino acid receptor antagonism in this model and suggest that combination of these two therapeutic approaches may yield additional benefit in treatment of thromboembolic stroke, particularly in cases where deep brain (end-artery-supplied) structures are affected.

Animals↗

Reduction of infarct volume by thrombolysis with rt-PA in an embolic rat stroke model.

Thrombolytic therapy with recombinant tissue plasminogen activator was tested in an embolic stroke model. In rats the internal carotid territory was embolized through the internal carotid artery with 50 microliters thrombin-rich (n = 18), 50 microliters thrombin-poor (n = 17) and 20 microliters thrombin poor (n = 13) suspension of arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial 133Xe injection method. Fifteen minutes after embolization 19 animals were treated with tissue plasminogen activator 20 mg kg-1, and 22 animals with saline. Carotid angiography displayed the degree of occlusion of the cerebral arterial supply before and after treatment. Brains were evaluated neuropathologically and infarct volume measured. Cerebral blood flow was reduced 72% after embolization with 50 microliters emboli suspension and 32% after embolization with 20 microliters suspension. The comparison of pre- and post-treatment angiography showed some recanalization in the treated animals, control animals had no recanalization. Thrombolytic therapy reduced the infarct volume from 72.8% to 20.9% of embolized hemisphere volume (p = 0.0037) in the 50-microliters thrombin rich-embolized group, from 22.9 to 9.0 (NS) in the 50-microliters-thrombin-poor-embolized group and from 6.6 to 0.0 (NS) in the 20-microliters-embolized group. One third of treated animals recanalized completely and developed smaller (p = 0.03) infarcts than the non-recanalized. No hemorrhagic complications were observed. Early thrombolytic therapy reduced infarct volume after embolic stroke in this model, this effect was dependent upon recanalization.

Animals↗

Alteplase therapy in acute ischemic stroke: a Danish pilot study.OFF.

In the period from October 1990 to December 1991, 23 patients with acute ischemic stroke were treated with recombinant tissue plasminogen activator (rt-PA) at a median of 205 min (range 78-355 min) after symptom onset. In this open pilot study rt-PA was given intravenously after an acute CT scan had not shown acute changes. In 12 patients regional cerebral blood flow was measured intravenously using 99mTc-HMPAO before and within 24 h after thrombolytic therapy. Reperfusion of the ischemic area was obtained in 10 patients. In these patients clinical improvement was greater the shorter the delay from symptom onset to initiation of treatment. Three of the 23 patients died, one of a parenchymatous hematoma, one of a large middle cerebral artery infarct, and one of acute myocardial infarction.

Cerebral Infarction↗

Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study.

OBJECTIVE: To study the dose related response of salmon calcitonin (salcatonin) given intranasally on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 208 healthy women aged 68-72 years who had a bone mineral content of the distal forearm on average 30% below the mean value for healthy premenopausal women. INTERVENTIONS: The 208 women were allocated randomly in blocks of four to two years of treatment with either salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups received a calcium supplement of 500 mg. 32 of the women left the study before its end and 164 women complied with the study criteria throughout. MAIN OUTCOME MEASURES: Bone mineral content of the distal forearm and lumbar spine and rates of vertebral and peripheral fractures after two years of treatment. RESULTS: The average changes in bone mineral content of the spine showed positive outcomes of 1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU. There was a significant dose related response to salcatonin, manifested by an increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new fractures was reduced significantly in the women treated with salcatonin to about one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07 to 0.77)). CONCLUSION: The results suggest that, compared with calcium alone, salcatonin given intranasally reduces the rates of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.

Administration, Intranasal↗

Discriminatory ability of bone mass measurements (SPA and DEXA) for fractures in elderly postmenopausal women.

We investigated the discriminatory ability of forearm bone mineral content (BMCarm) measured by single photon absorptiometry (SPA) and spinal bone mineral density (BMDspine) measured by dual-energy X-ray absorptiometry (DEXA) in 387 elderly postmenopausal women. Of these, 22 had never sustained a fracture (normal), 91 had had less than three vertebral wedge fractures (mild), 51 had experienced a peripheral fracture (moderate), and 24 had had more than three vertebral wedge or compression fractures (severe). BMCarm exceeded BMDspine slightly in the ability to discriminate the mild and moderate groups (P less than 0.01-0.001), whether calculations were performed on raw values or the Z-scores compared with premenopausal women. Receiver operating (ROC) analysis showed that at every cutoff level BMCarm had a similar ability as BMDspine to discriminate between the vertebral fracture (mild and severe) groups and healthy premenopausal and nonfractured postmenopausal women (normal), whereas BMCarm had a significantly higher discriminatory ability of peripheral fractures (P less than 0.05) (moderate) group compared with premenopausal women. We conclude that SPA and DEXA are equally capable as diagnostic procedures in women with established osteoporosis.

Absorptiometry, Photon↗

Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis.

In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P less than 0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P less than 0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P less than 0.05-0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxy-proline/creatinine) did not change during the observational period, but significantly declined, 10-30%, during sCT treatment (P less than 0.01-0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women.

Administration, Rectal↗

No secular increase in the prevalence of vertebral fractures due to postmenopausal osteoporosis.

We examined whether the prevalence of vertebral fractures in otherwise healthy, 70-year-old Danish women had increased during an interval of 10 years. The population-based epidemiological study included two age-matched groups of postmenopausal women. Group 1 consisted of 70-year-old women (n = 386) living in a defined area of suburban Copenhagen recruited in 1979 for an epidemiological study. Of the 285 women who were entered, 173 were judged healthy, without secondary causes of osteoporosis. Group 2 was recruited by sending questionnaires to all women aged 68-72 years living in the same area in 1989. Of the 512 women who attended a medical screening, 387 were found to be without secondary causes of osteoporosis and had a spinal radiograph. Radiographs of the thoracolumbar spine were assessed for vertebral fracture by five radiological methods. There was no significant difference between the two groups in the prevalence of vertebral fractures and the 95% confidence intervals overlapped completely in all methods. The prevalence rates varied by method from about 35% to more than 80% but the distribution of fracture types was similar in the two groups. We conclude that the prevalence of vertebral fractures due to postmenopausal osteoporosis has not increased since 1979 in otherwise healthy women residing in suburban Copenhagen, and that comparison of prevalences between studies requires that they use the same method of radiological assessment.

Aged↗

A rat model of reproducible cerebral infarction using thrombotic blood clot emboli.

The purpose of this study was the development of a model of embolic stroke with high reproducibility concerning infarct volume. In 37 male Sprague-Dawley rats, the internal carotid artery was embolized with in vitro preformed suspensions of autologous microemboli resembling arterial thrombi. With a method of continuous flow through the carotid arterial catheter, reflux of blood with uncontrolled clotting and embolization was avoided, thereby providing control animals free of ischemic damage. The embolized animals had arterial occlusions on angiograms immediately after embolization and no spontaneous recanalization on angiograms 2 h later. The cerebral blood flow measured by the intra-arterial 133Xe injection method decreased to 21-37% of baseline values. All embolized animals developed hemiparesis with spontaneous circling behavior, embolization with more than 150 microliters clot suspension resulted in hemispherical infarcts. There was a strong statistically significant correlation between amount of emboli, rate of vascular occlusion, and volume of infarcted tissue. This is the first model presented utilizing autologous in vitro microemboli imitating "white" arterial thrombi. The animals developed infarction, resembling human stroke.

Angiography↗