Hängt das Ergebnis einer Thrombolyse mit rekombinantem Gewebe-Plasminogenaktivator (rt-PA) beim Kaninchen vom Erythrozyten- und Fibringehalt eines Thrombus ab?

 

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Zusammenfassung

Ziel: Zu überprüfen, ob der Erfolg einer Lyse mit rekombinantem Gewebe-Plasminogenaktivator (rt-PA) vom Erythrozyten- und Fibringehalt eines Thrombus abhängt. Methode: 30 Minuten nach Verschluss der A. cerebri media mit 20 Stunden alten roten oder weißen Emboli wurde bei 23 Kaninchen eine intraarterielle Thrombolyse mit 3 mg rt-PA/kg Körpergewicht durchgeführt. 20 Kaninchen dienten als Kontrolle. Die zerebrale Perfusion wurde MR-tomographisch überwacht. Ergebnisse: rt-PA entfaltete nur bei Gefäßverschlüssen mit roten Emboli eine thrombolytische Wirkung. In dieser Gruppe sank die mittlere Transitzeit des Kontrastmittels durch das Hirngewebe (NFM; p < .05), das relative regionale Blutvolumen (rrCBV) normalisierte sich (p < .05), und die Infarktgröße nahm ab (p < .01). Bei weißen Emboli hatte rt-PA keinen Einfluss auf die Hirndurchblutung und die Infarktgröße. Schlussfolgerungen: In unserem Tierversuch nahm die thrombolytische Wirkung von rt-PA mit dem Erythrozytengehalt der Gefäßverschlüsse zu und mit ihrem Fibringehalt ab. Sollte dieses Ergebnis auch auf Schlaganfallpatienten zutreffen, wäre es denkbar, dass der Erfolg einer Lyse noch vor Therapiebeginn abgeschätzt werden kann, denn rote und weiße Thromben lassen sich durch ihre Röntgendichte unterscheiden.

Abstract

Purpose: It is known from autopsy studies that thromboembolic stroke can be caused by red, white and mixed clots. We therefore examined whether the efficacy of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) depends on the proportions of fibrin and erythrocytes within thromboembolic material. Methods: In 23 rabbits intraarterial thrombolysis with 3 mg rt-PA/kg body weight was started 30 minutes after middle cerebral artery occlusion with either red or white autologous emboli 20 hours old. 20 rabbits served as control. Cerebral perfusion was monitored by MRI. Results: rt-PA enhanced lysis of red but not of white emboli and decreased the infarct volume only if vascular occlusion was due to red emboli (p < .01). Cerebral perfusion improved only in the red treatment group where the normalized first moment (NFM) decreased (p < .05) and the relative regional cerebral blood volume (rrCBV) reached normal values (p < .05). Conclusion: We suggest that in our animal model the efficacy of thrombolysis increases with the proportion of erythrocytes within thromboembolic material and decreases with its content of fibrin. lf these findings would also be applicable to patients, pretherapeutic estimation of the efficacy of thrombolysis might become feasible because the CT values of red and white thrombi differ.

Literatur

• 1 Bednar M M, Mc Auliffe T, Raymond S, Gross C E. Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.  Stroke. 1990;  21 1705-1709
  PubMedGoogle Scholar
• 2 Benes V, Zabramski J M, Boston M, Puca A, Spetzler R F. Effect of intra-arterial tissue plasminogen activator and urokinase on autologous arterial emboli in the cerebral circulation of rabbits.  Stroke. 1990;  21 1594-1599
  PubMedGoogle Scholar
• 3 Hamilton M G, Lee J S, Cummings P J, Zabramski J M. A comparison of intra-arterial and intravenous tissue-type plasminogen activator on autologous arterial emboli in the cerebral circulation of rabbits.  Stroke. 1994;  25 651-656
  PubMedGoogle Scholar
• 4 Gross C E, Raymond S J, Howard D B, Bednar M M. Delayed tissue-plasminogen activator therapy in a rabbit model of thromboembolic stroke.  Neurosurgery. 1995;  36 1172-1177
  PubMedGoogle Scholar
• 5 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke.  N Engl J Med. 1995;  333 1581-1587
  CrossrefPubMedGoogle Scholar
• 6 Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, Kummer R von, Boysen G, Bluhmki E, Höxter G, Mahagne M H, Hennerici M. for the ECASS Study Group . Intravenous thrombolysis with recombinant tissue plas-minogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS).  JAMA. 1995;  274 1017-1025
  CrossrefPubMedGoogle Scholar
• 7 Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. for the Second European-Australasian Acute Stroke Study Investigators . Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II).  Lancet. 1998;  352 1245-1251
  CrossrefPubMedGoogle Scholar
• 8 Steiner T, Bluhmki E, Kaste M, Toni D, Trouillas P, von Kummer R, Hacke W. for the ECASS Study Group . The ECASS 3-hour cohort. Secondary analysis of ECASS data by time stratification.  Cerebrovasc Dis. 1998;  8 198-203
  PubMedGoogle Scholar
• 9 del Zoppo G J. Clinical trials in acute stroke: why have they not been successful?.  Neurology. 1998;  51 (3 Suppl 3) S 59-S 61
  PubMedGoogle Scholar
• 10 Hacke W, Brott T, Caplan L, Meier D, Fieschi C, Kummer R von, Donnan G, Heiss W D, Wahlgren N G, Spranger M, Boysen G, Marler J R. Thrombolysis in acute ischemic stroke: controlled trials and clinical experience.  Neurology. 1999;  53 (7 Suppl. 4) S 3-S 14
  PubMedGoogle Scholar
• 11 Vanderschueren S, Van Vlaenderen I, Collen D. Intravenous thrombolysis with recombinant staphylokinase versus tissue-type plasminogen activator in a rabbit embolic stroke model.  Stroke. 1997;  28 1783-1788
  PubMedGoogle Scholar
• 12 Yenari M A, Lee L K, Beaulieu C, Sun G H, Kunis D, Chang D, Albers G W, Moseley M E, Steinberg G K. Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke.  J Stroke Cerebrovasc Dis. 1998;  7 179-186
  PubMedGoogle Scholar
• 13 Castaigne P, Lhermitte F, Gautier J C, Escourolle R, DerouesneŽ C. Internal carotid artery occlusion. A study of 61 instances in 50 patients with post-mortem data.  Brain. 1970;  93 231-258
  PubMedGoogle Scholar
• 14 Jörgensen L, Torvik A. Ischaemic cerebrovascular diseases in an autopsy series. Part 2. Prevalence, location, pathogenesis, and clinical course of cerebral infarcts.  J Neurol Sci. 1969;  9 285-320
  CrossrefPubMedGoogle Scholar
• 15 Torvik A, Jörgensen L. Thrombotic and embolic occlusions of the carotid arteries in an autopsy series. Part 2. Cerebral lesions and clinical course.  J Neurol Sci. 1966;  3 410-432
  CrossrefPubMedGoogle Scholar
• 16 Kirchhof K, Welzel T, Zoubaa S, Lichy C, Sikinger M, Lorbacher de Ruiz H, Sartor K. New method of embolus preparation for standardized embolic stroke in rabbits.  Stroke. 2002;  33 2329-2333
  CrossrefPubMedGoogle Scholar
• 17 Golanov E V, Reis D J. Contribution of cerebral edema to the neuronal salvage elicited by stimulation of cerebellar fastigial nucleus after occlusion of the middle cerebral artery in rat.  J Cereb Blood Flow Metab. 1995;  15 172-174
  PubMedGoogle Scholar
• 18 Urban I, Richard P. A stereotaxic atlas of the New Zealand rabbit's brain.  Springfield, Illinois, USA C C Thomas. 1972;  1 76-81
  PubMedGoogle Scholar
• 19 Fisel C R, Ackerman J L, Buxton R B, Garrido L, Belliveau J W, Rosen B R, Brady T J. MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology.  Magn Reson Med. 1991;  17 336-347
  PubMedGoogle Scholar
• 20 Rosen B R, Belliveau J W, Vevea J M, Brady T J. Perfusion imaging with NMR contrast agents.  Magn Reson Med. 1990;  14 249-265
  CrossrefPubMedGoogle Scholar
• 21 Blinc A, Keber D, Lahajnar G, Stegnar M, Zidansek A, Demsar F. Lysing patterns of retracted blood clots with diffusion or bulk flow transport of plasma with urokinase into clots - a magnetic resonance imaging study in vitro.  Thromb Haemost. 1992;  68 667-671
  PubMedGoogle Scholar
• 22 Carr M E, Hardin C L. Fibrin has larger pores when formed in the presence of erythrocytes.  Am J Physiol. 1987;  253 H 1069-H 1073
  PubMedGoogle Scholar
• 23 Jørgensen L. Experimental platelet and coagulation thrombi.  Acta Path et Microbiol Scandinav. 1964;  62 189-223
  PubMedGoogle Scholar
• 24 Chapman I. Morphogenesis of occluding coronary artery thrombosis.  Arch Path. 1965;  80 256-261
  PubMedGoogle Scholar
• 25 Rodman N F, Painter J C, Mc Devitt N B. Platelet disintegration during clotting.  J Cell Biol. 1963;  16 225-241
  CrossrefPubMedGoogle Scholar
• 26 Brown B G, Gallery C A, Badger R S, Kennedy J W, Mathey D, Bolson E L, Dodge H T. Incomplete lysis of thrombus in the moderate underlying atherosclerotic lesion during intracoronary infusion of streptokinase for acute myocardial infarction: quantitative angiographic observations.  Circulation. 1986;  73 653-661
  PubMedGoogle Scholar
• 27 Ueda T, Hatakeyama T, Kumon Y, Sakaki S, Uraoka T. Evaluation of risk of hemorrhagic transformation in local intra-arterial thrombolysis in acute ischemic stroke by initial SPECT.  Stroke. 1994;  25 298-303
  PubMedGoogle Scholar
• 28 Xi G, Hua Y, Bhasin R R, Ennis S R, Keep R F, Hoff J T. Mechanisms of edema formation after intracerebral hemorrhage: effects of extravasated red blood cells on blood flow and blood-brain barrier integrity.  Stroke. 2001;  32 2932-2938
  PubMedGoogle Scholar
• 29 Kirchhof K, Welzel T, Mecke C, Zoubaa S, Sartor K. Differentiation of white, mixed, and red thrombi: value of CT in estimation of the prognosis of thrombolysis - phantom study.  Radiology. 2003;  228 126-130
  PubMedGoogle Scholar
• 30 Kirchhof K, Mecke C, Lichy C, Sartor K. Die Röntgendichte am Ort thrombembolischer zerebraler Gefäßverschlüsse: Prognostischer Faktor für eine Lysetherapie?.  Fortschr Röntgenstr. 2003;  175 1130-1137
  PubMedGoogle Scholar

Dr. Klaus Kirchhof

Klinik für Diagnostische Radiologie und Neuroradiologie, Zentralklinikum Augsburg

Stenglinstraße 2

86156 Augsburg

Phone: ++49/821/400-2441

Fax: ++49/821/400-3312

Email: Klaus.Kirchhof@radiologie.zk.augsburg-med.de