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ABSTRACT: 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.
Acta Neurologica Scandinavica 09/1994; 90(2):91-8. · 2.47 Impact Factor
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ABSTRACT: The effect of body temperature on cerebral infarcts and thrombolytic therapy was investigated in 91 rats embolized in the right carotid territory. Hypothermia of 32 degrees C for 2 h with preembolic onset (n = 15) or hyperthermia of 39 degrees C for 2 h with postembolic onset (n = 22) was compared to normothermic controls (n = 17). After 48 h of survival, neuropathological evaluation with measurement of infarct volume was performed. Median infarct volume in percent of affected hemisphere volume was 11% (9-21, quartiles) in rats treated with hypothermia alone, compared to 46% (14-59, quartiles) in normothermic controls (P = 0.04). Hyperthermia for 2 h increased median infarct volume to 65% (37-75, quartiles). There was a positive and significant correlation between infarct volume and body temperature (R = 0.53, P = 0.0002, n = 54). Mortality rate was significantly higher among rats treated with hyperthermia compared to normothermic controls (P = 0.005). A subset of 37 rats exposed to the same temperature regimen were treated with tissue plasminogen activator (20 mg/kg i.v. during 45 min) 2 h after embolization. Judged by posttreatment carotid angiography, hyperthermic rats (n = 11) had the best degree of recanalization (P = 0.03) compared to controls (n = 17), but median infarct volume in this group was (58% (27-67, quartiles)) significantly larger (P < 0.02) than normothermic (21% (15-39, quartiles), n = 14) and hypothermic (13% (7-31, quartiles), n = 12) rats treated with thrombolytic therapy. Thrombolytic therapy following 2 h of hypothermia, could not improve the effect of hypothermia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research 06/1994; 647(1):131-8. · 2.73 Impact Factor
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ABSTRACT: 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.
Journal of Cerebral Blood Flow & Metabolism 05/1994; 14(3):472-7. · 5.01 Impact Factor
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ABSTRACT: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow.
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.
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.
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.
Stroke 11/1993; 24(10):1439-46. · 5.73 Impact Factor
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ABSTRACT: 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)
Neurological Research 10/1993; 15(5):344-9. · 1.52 Impact Factor
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ABSTRACT: 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.
Scandinavian Journal of Clinical and Laboratory Investigation 08/1993; 53(4):383-93. · 1.38 Impact Factor
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ABSTRACT: 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.
Zeitschrift für Kardiologie 02/1993; 82 Suppl 2:105-8. · 0.97 Impact Factor
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ABSTRACT: The efficacy and safety of thrombolysis with different dose regimens of recombinant tissue plasminogen activator (rt-PA) and its combination with aspirin was tested in an embolic stroke model. In rats the carotid territory was embolized with a single clot formed in a polyethylene tube and washed with saline. Fifteen minutes after embolization 10 animals were treated with rt-PA 10 mg kg-1; 11 with 15 mg kg-1; 12 with 20 mg kg-1 and 9 with 10 mg kg-1 + 20 mg kg-1 aspirin and 34 animals with saline. Rt-PA 10 mg kg-1 reduced median infarct volume (in percent of the ipsilateral hemisphere volume) from 19.5 to 4.8; rt-PA 15 mg kg-1 to 2.0; rt-PA 20 mg kg-1 to 0.0, while rt-PA 10 mg kg-1 + aspirin resulted in a median infarct volume of 9.5%. Thrombolytic therapy significantly and dose dependently (p = 0.001) reduced the infarct volume, improved the presacrifice clinical score and increased (p = 0.02) angiographically verified reperfusion. There was no additional benefit of coadministration of aspirin.
Neuroreport 11/1992; 3(10):925-8. · 1.66 Impact Factor
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ABSTRACT: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model.
The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured.
Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p = 0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p = 0.007) and increased the survival rate from 0.48 to 0.96 (p = 0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed.
Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model.
Stroke 09/1992; 23(8):1167-73; discussion 1174. · 5.73 Impact Factor
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ABSTRACT: 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.
Journal of Cerebral Blood Flow & Metabolism 06/1992; 12(3):484-90. · 5.01 Impact Factor
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Neurological Research 07/1990; 12(2):81-2. · 1.52 Impact Factor
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ABSTRACT: This report describes three patients, with acute cerebral arterial occlusion, treated with recombinant tissue plasminogen activator (rt-PA). In one patient with basilar artery occlusion thrombolytic treatment was initiated 12 h after onset of the symptoms. In two patients with angiographically verified occlusion of the middle cerebral artery, the treatment was initiated approximately 4.5 h after onset of the symptoms. Recombinant tissue plasminogen activator 80-120 mg, was infused intra-arterially over 90-100 min via a catheter the tip of which was close to the occlusion. This regimen resulted in recanalization in all the patients; however, in two patients it was verified by repeat CT scan only. In two patients the thrombolytic treatment was successful (the patients improved clinically); the third patient died of massive cerebral infarct-related oedema. In none of the patients did significant bleeding or other obvious side-effects occur. From this preliminary report it is concluded that angiographically proven thrombolytic recanalization in acute cerebrovascular occlusion is possible with rt-PA. In some patients, however, the treatment is initiated too late. Further investigation of the possible indication for thrombolytic therapy in stroke is needed.
Neurological Research 07/1990; 12(2):78-80. · 1.52 Impact Factor
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ABSTRACT: The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on regional cerebral blood flow (rCBF) was studied in 12 patients within 5 days after their first acute stroke. rCBF was studied by xenon-133 inhalation and single-photon emission computed tomography (SPECT) scan before and 1 h after oral administration of 25 mg captopril. No increase in rCBF was observed in any of the 12 patients included in the study. In only one patient was there a slight redistribution of blood flow in favor of the low-flow area, but the absolute flow value did not increase. Captopril did not cause any significant change in mean hemispheric blood flow, mean arterial blood pressure (MAP), or end-expiratory CO2 fraction (FECO2). The assumption that ACE inhibition might increase cerebral blood flow in the periinfarct zone and preserve some still viable brain tissue could not be verified in the present study.
Journal of Cardiovascular Pharmacology 12/1989; 14(5):722-9. · 2.29 Impact Factor
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ABSTRACT: Background and purpose: The efficacy of thrombolysis with recombinant tissue plasminogen activator and its dependency upon clot composition was tested in an embolic stroke model.Methods: In 53 rats the carotid territory was embolised with two arterial-like type of clots and one venous-like type of clot. The arterial ones were either fibrin poor (group A) or fibrin rich (group B). Hemispheric cerebral blood flow before and after embolisation was measured by intraarterial 133 Xenon injection method. 15 min after embolisation 18 animals were treated with tissue plasminogen activator 20mg/kg, and 35 animals with saline. 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 volume measured.Results: Cerebral blood flow was reduced by 36 to 62% after embolisation. The comparison of post-treatment angiography of treated animals to controls in group embolised with arterial-like fibrin rich clots showed significant (p=0.0163) reperfusion in thrombolytic treated animals. Thrombolytic therapy significantly reduced the infarct volume from 11.6 to 1.9% of embolised hemisphere volume (p=0.019) in group embolised with fibrin-poor clots and from 18.3 to 0.0% (p=0.0001) in the group embolised with fibrin-rich clots. Among the treated animals embolised with fibrin rich clots, both the completely recanalised animals (p=0.0003) and the partially recanalised animals (p=0.027) developed smaller infarctions than control animals. No hemorrhagic complications were observed. The control animals embolised with venous-like clots recanalised spontaneously and developed almost no infarctions and only temporary clinical damage.Conclusions: Early thrombolytic therapy induced recanalisation and reduced infarct volume after embolic stroke, this effect was particularly apparent in the group embolised with fibrin-rich clots.
Fibrinolysis.
