Optimal thrombolytic strategies for acute myocardial infarction--bolus administration.
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Optimal strategies for thrombolysis in myocardial infarction (TIMI) are still being sought because the TIMI 3 flow rates achievable using standard regimens average approximately 60%. Double bolus administration of recombinant tissue plasminogen activator (tPA) is a novel approach with potential for earlier patency combined with ease of administration. We reviewed total patency rates, TIMI 3 patency rates, mortality, stroke and intracranial haemorrhage rates in the major trials of accelerated infusion tPA/bolus tPA/reteplase in acute myocardial infarction. A direct comparison was performed with results of two recent trials of double bolus (two 50 mg boli, 30 min apart) vs. accelerated infusion tPA: the Double Bolus Lytic Efficacy Trial (DBLE), an angiographic study, and the COBALT Trial, a mortality study. The DBLE trial showed equivalent patency rates for accelerated infusion and double bolus administration of tPA. Reviewing other angiographic trials, total patency and TIMI 3 patency rates achievable with double bolus tPA were comparable to those with accelerated infusion tPA or bolus reteplase administration. The COBALT study demonstrated a 30-day mortality of 7.53% in patients treated with accelerated infusion tPA compared with 7.98% for double bolus tPA treated patients. The small excess in mortality with double bolus treatment was confined to the elderly; in those < or = 75 years, mortality rates were 5.6% and 5.7%, for double bolus and accelerated infusion, respectively, and rates for death or non-fatal stroke were 6.35% and 6.3%, respectively. Comparison with other trials demonstrated mortality, stroke and intracranial haemorrhage rates with double bolus treatment similar to those associated with either accelerated infusion tPA or bolus reteplase treatment. Double bolus administration of tPA to patients with acute myocardial infarction is associated with total patency, TIMI 3 patency, mortality, stroke and intracranial haemorrhage rates similar to those associated with either accelerated infusion of tPA or bolus reteplase. (+info)
Isolation of SMTP-3, 4, 5 and -6, novel analogs of staplabin, and their effects on plasminogen activation and fibrinolysis.
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Four novel triprenyl phenol metabolites, designated SMTP-3, -4, -5, and -6, have been isolated from cultures of Stachybotrys microspora IFO 30018 by solvent extraction and successive chromatographic fractionation using silica gel and silica ODS columns. A combination of spectroscopic analyses showed that SMTP-3, -4, -5, and -6 are staplabin analogs, containing a serine, a phenylalanine, a leucine or a tryptophan moiety in respective molecules in place of the N-carboxybutyl portion of the staplabin molecule. SMTP-4, -5, and -6 were active at 0.15 to 0.3 mM in enhancing urokinase-catalyzed plasminogen activation and plasminogen binding to fibrin, as well as plasminogen- and urokinase-mediated fibrinolysis. On the other hand, the concentration of staplabin required to exert such effects was 0.4 to 0.6 mM, and SMTP-3 was inactive at concentrations up to 0.45 mM. (+info)
Two similar cases of encephalopathy, possibly a reversible posterior leukoencephalopathy syndrome: serial findings of magnetic resonance imaging, SPECT and angiography.
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Two young women who had encephalopathy that resembled reversible posterior leukoencephalopathy syndrome are presented. The brain magnetic resonance imaging (MRI) of these patients exhibited similar T2-high signal lesions, mostly in the white matter of the posterior hemispheres. Xe-SPECT during the patients' symptomatic period showed hypoperfusion in the corresponding areas, and angiography demonstrated irregular narrowing of the posterior cerebral artery. Clinical manifestations subsided soon after treatment, and the abnormal radiological findings also were almost completely resolved. Thus, we concluded that transient hypoperfusion followed by ischemia and cytotoxic edema might have had a pivotal role in these cases. (+info)
Combination therapy of fasudil hydrochloride and ozagrel sodium for cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
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Fasudil hydrochloride is a new type of intracellular calcium antagonist, different from the calcium entry blockers that are commonly employed for clinical use. Since September 1995, the combination of fasudil hydrochloride and ozagrel sodium, an inhibitor of thromboxane A2 synthesis, has been used to treat 60 patients at risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The effectiveness of this combination therapy was investigated by comparison with the outcome of 57 patients previously treated with only ozagrel sodium. The combination therapy was significantly more effective (p < 0.01) in reducing the incidence of low density areas on computed tomography scans, and reduced, but not significantly, the occurrence of symptomatic vasospasm. The combination therapy of fasudil hydrochloride and ozagrel sodium has superior effectiveness over only ozagrel sodium in treating patients at risk of vasospasm after aneurysmal subarachnoid hemorrhage. (+info)
Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin.
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BACKGROUND AND PURPOSE: We chose to evaluate the safety and efficacy of combined intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT). METHODS: We treated 12 patients with symptoms of 1 to 40 days' duration (eg, headache, somnolence, focal deficits, seizures, and nausea and vomiting). Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients, obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3 patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and 1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused concomitantly. RESULTS: Flow was restored completely in 6 patients and partially in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29 hours (range, 13 to 77 hours). Symptoms improved in these 9 patients concomitantly with flow restoration. Flow could not be restored in 3 patients. In 1 of them, treatment was stopped when little progress had been made, and fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1 of these, the hematoma was evacuated. CONCLUSIONS: Our experience with intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT is encouraging. This therapy should probably be regarded as unsafe in patients with obvious hemorrhage. Time to restore flow may be faster than with urokinase (an average of 71 hours has been reported for 29 documented patients). Further evaluation of rtPA with heparin in CVT is warranted. (+info)
Delayed increase in infarct volume after cerebral ischemia: correlations with thrombolytic treatment and clinical outcome.
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BACKGROUND AND PURPOSE: Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome. METHODS: Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS: Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups. CONCLUSIONS: In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment. (+info)
Thrombolysis with tissue plasminogen activator alters adhesion molecule expression in the ischemic rat brain.
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BACKGROUND AND PURPOSE: We tested the hypothesis that treatment of embolic stroke with recombinant human tissue plasminogen activator (rhtPA) alters cerebral expression of adhesion molecules. METHODS: Male Wistar rats were subjected to middle cerebral artery occlusion by a single fibrin-rich clot. P-selectin, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) immunoreactivity was measured at 6 or 24 hours after embolic stroke in control rats and in rats treated with rhtPA at 1 or 4 hours after stroke. To examine the therapeutic efficacy of combined rhtPA and anti-ICAM-1 antibody treatment at 4 hours after embolization, ischemic lesion volumes were measured in rats treated with rhtPA alone, rats treated with rhtPA and anti-ICAM-1 antibody, and nontreated rats. RESULTS: Administration of rhtPA at 1 hour after embolization resulted in a significant reduction of adhesion molecule vascular immunoreactivity after embolization in the ipsilateral hemisphere compared with corresponding control rats. However, when rhtPA was administered to rats at 4 hours after embolization, significant increases of adhesion molecule immunoreactivity in the ipsilateral hemisphere were detected. A significant increase of ICAM-1 immunoreactivity was also detected in the contralateral hemisphere at 24 hours after ischemia. A significant reduction in lesion volume was found in rats treated with the combination of rhtPA and anti-ICAM-1 antibody compared with rats treated only with rhtPA. CONCLUSIONS: The present study suggests that the time of initiation of thrombolytic therapy alters vascular immunoreactivity of inflammatory adhesion molecules in the ischemic brain and that therapeutic benefit can be obtained by combining rhtPA and anti-ICAM-1 antibody treatment 4 hours after stroke. (+info)
Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI.
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BACKGROUND: Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined. CASE DESCRIPTION: The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused. CONCLUSIONS: Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy. (+info)