Unit:
Library of the School of Health SciencesΤομέας Παθολογίας
Dissertation committee:
Νανάς Ιωάννης, Καθηγητής, Γ Καρδιολογική Κλινική, Πανεπιστήμιο Αθηνών
Νανά- Αναστασίου Μαρία, Καθηγήτρια, Β Καρδιολογική Κλινική, Πανεπιστήμιο Αθηνών
Τουμανίδης Σάββας, Καθηγητής, Θεραπευτική Κλινική, Πανεπιστήμιο Αθηνών, Νοσοκομείο Αλεξάνδρα
Περρέα Δέσποινα, Καθηγήτρια, Πειραματική Φαρμακολογία, Πανεπιστήμιο Αθηνών
Παρασκευαίδης Ιωάννης, Αναπληρωτής Καθηγητής, Θεραπευτική Κλινική, Πανεπιστήμιο Αθηνών, Νοσοκομείο Αλεξάνδρα
Καστρίτης Ευστάθιος, Αναπληρωτής Καθηγητής, Θεραπευτική Κλινική, Πανεπιστήμιο Αθηνών, Νοσοκομείο Αλεξάνδρα
Σανούδου Δέσποινα, Επίκουρη Καθηγήτρια, Φαρμακολογία, Πανεπιστήμιο Αθηνών
Original Title:
Αποτελεσματικότητα της μειωμένης δόσης θρομβόλυσης σε συνδυασμό με αντιθρομβωτική αγωγή σε πειραματικό μοντέλο πρόκλησης θρόμβου
Translated title:
Efficacy of low dose tenecteplase in restoring vessel patency in a clinically relevant large animal experimental model.
Summary:
Background: We tested the hypothesis that low dose tenecteplase, a recombinant fibrin-specific plasminogen activator can induce efficient thrombolysis even in lower doses than the hitherto indicated, compared to full-dose thrombolytic therapy for STsegment myocardial infarction.
Methods: Farm pigs (30-35kg, n=15) were imposed in a clinically relevant model of thrombosis. We used both the common carotid arteries and the left anterior descending artery below the first diagonal. The vessels were initially externally injured (application
of pressure by forceps) followed by an appropriate for the vessel dose of thrombin (100IU for the LAD and 190 IU for CA). Occluding thrombi was achieved in 80% for the LAD and 57% for the CA. Ten minutes post occlusion the animals were allocated under
continuous electrocardiogram and ultrasonic flow meter monitoring to one of the following groups: Group A) half-dose tenecteplase (2000IU); Group B) Full dose tenecteplase (5000IU); Group C) saline only. All animals received 60IU heparin and
antiplatelet agents. The follow-up was 120 minutes post therapy administration.
Results: Sixty minutes after lytic drug administration recanalization occurred in 58% of the occluded arteries in Group A, in 85% in Group B and in 20% in Group C (P=0.028). Both tenecteplase regimens were effective for treating carotid artery thrombosis (71%
Group A vs 75% in Group B vs 33% in Group C, P=0.286), but low dose was significantly less effective in reestablishing flow in proximally occluded LADs (25 % in
Group A vs 100% in Group B vs 0% in Group C, P=0.015). All vessels with restored flow at 60 minutes remained patent at least for 1hr. In Group A, at 60 minutes after tenecteplase administration, flow velocity in LAD reached 30% of the baseline value and
45% in carotids, while in Group B flow was 160% and 55% respectively, suggesting restoration of larger lumen diameter in the treated vessels. Post reperfusion ventricular
arrhythmias that required treatment occurred equally in all groups. No differences in hemodynamic or blood coagulation tested parameters were observed between the groups.
Conclusions: The arterial thrombosis model developed in the current study appears clinically relevant and useful for testing the efficacy of different thrombolytic regimens. Our data demonstrate that low dose tenecteplase can be successfully used for treating
thrombosis of larger diameter vessels, such as the carotids, but appears inadequate for treating LAD thrombotic occlusions.
Main subject category:
Cardiovascular diseases
Other subject categories:
Pharmaceutical technology
Keywords:
Acute myocardial infarction
Thrombolysis
Ischemic Stroke
Number of references:
182
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Eleni Tseliou PhD 2017.pdf
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