Document Detail


Validation of the use of long-term indwelling jugular catheters in a rat model of cardiotoxicity.
MedLine Citation:
PMID:  16995648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Doxorubicin administered to rats induces a dose-dependent cardiomyopathy. Both doxorubicin administration and the presence of indwelling catheters have been associated with thrombus formation. We sought to determine feasibility of drug delivery and degree of thrombogenesis related to long-term indwelling catheter use in a cardiotoxicity model. Rats receiving doxorubicin or saline via jugular catheters coated with end-point immobilized heparin were compared to rats receiving similar treatments via direct jugular intravenous injection (venotomy). Onset of cardiotoxicity, defined by reduction in fractional shortening to 45% or less, was determined by echocardiography. Thrombogenesis was assessed by observation of atrial thrombi and pulmonary emboli as determined by post-mortem and histologic examination. Significantly more of the doxorubicin-treated and catheterized group (87.5%) developed cardiotoxicity relative to the doxorubicin-treated-venotomized group (28.6%), as indicated by an earlier and more precipitous decline in fractional shortening in the doxorubicin-treated-catheterized rats. Despite this change, rats from catheterized groups demonstrated improved weight maintenance relative to venotomy groups. Although the number of pulmonary emboli did not differ significantly between groups, 50% of the doxorubicin-treated-catheterized animals developed vegetative endocarditis. Despite alteration of the model-induced cardiac disease, we submit that the more reliable and early induction of the desired endpoint, in addition to improved weight maintenance, represent model refinements. The ease of drug delivery with minimal restraint and no anesthesia is an additional and important benefit. The development of vegetative endocarditis represents an opportunity to study the formation and prevention of this condition.
Authors:
Lynn M Wachtman; Michelle D Browning; Djahida Bedja; Scott Pin; Kathleen L Gabrielson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Validation Studies    
Journal Detail:
Title:  Journal of the American Association for Laboratory Animal Science : JAALAS     Volume:  45     ISSN:  1559-6109     ISO Abbreviation:  J. Am. Assoc. Lab. Anim. Sci.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-25     Completed Date:  2006-10-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  101269489     Medline TA:  J Am Assoc Lab Anim Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  55-64     Citation Subset:  IM    
Affiliation:
Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / toxicity
Body Weight / drug effects
Cardiomyopathies / chemically induced,  pathology*,  physiopathology
Catheters, Indwelling / adverse effects*
Disease Models, Animal*
Dose-Response Relationship, Drug
Doxorubicin / toxicity
Echocardiography
Female
Heparin / therapeutic use
Jugular Veins
Rats
Rats, Sprague-Dawley
Thrombosis / etiology,  pathology*,  prevention & control
Time Factors
Grant Support
ID/Acronym/Agency:
RR07002/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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