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      Quantifying the Effect of Locally Delivered Anticoagulant Drugs: Modification of an in vivo Model of Venous Thrombosis

      , , ,

      Journal of Vascular Research

      S. Karger AG

      Vena cava, Vascular injury, Thrombosis, Thrombolysis

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          Abstract

          Increasingly, attention is focusing on the local delivery of antiplatelet and fibrinolytic therapy as a means of preventing intravascular thrombosis. A simple, reproducible model of thrombosis, based upon vascular damage is needed to test these agents in vivo. We have therefore modified a rat vena cava model of venous thrombosis based upon vascular injury and stasis. Wistar rats are anaesthetised, the inferior cava dissected free and a segment isolated by slings distally above the iliacs and proximally above the left renal vein. All other tributaries are ligated. Vascular injury is induced by externally applying soft-jaw clamps for 5 min. Agents to be tested are introduced into the isolated segment via a left renal vein cannula left in situ for 15 min and then flushed from the cava. Blood is allowed to refill the segment, all remaining slings are tied and the animal left for 30 min before being killed. The cava is then opened and thrombus removed and weighed. Scanning electron microscopy of the cava after clamping shows areas of normal endothelium interspersed with areas of denuded endothelium and exposed subendothelial connective tissue. Histological and immunohistochemical staining indicates the thrombus is composed of red cells, platelets and fibrin. The model was validated by assessing the effects of 2 different doses of locally delivered tissue-type plasminogen activator (tPA). The mean weights of thrombus were [mg (SD)]: Control (saline; n = 8) 39.0 (8.73), tPA 0.01 mg/ml (n = 6) 45.5 (10.56) and tPA 1 mg/ml (n = 8) 3.5 (3.4). Comparing 1 mg/ml tPA vs. 0.01 mg tPA vs. control, p < 0.001 (Mann-Whitney test). We have thus modified a simple, inexpensive, reproducible model for assessing the potential of locally delivered agents to reduce platelet-fibrin thrombus formation following vascular injury.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1993
          1993
          23 September 2008
          : 30
          : 6
          : 323-326
          Affiliations
          The Academic Department of Cardiology, Glenfield General Hospital, Leicester, UK
          Article
          159013 J Vasc Res 1993;30:323–326
          10.1159/000159013
          8241365
          © 1993 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 4
          Categories
          Research Paper

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