title: Validation of the use of long-term indwelling jugular catheters in a rat model of cardiotoxicity.
abstract: 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.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Wachtman
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Browning
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.forename: Scott
authors.initials: S
authors.lastname: Pin
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gabrielson
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D002408:Catheters, Indwelling / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity; D004452:Echocardiography; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D007601:Jugular Veins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D006493:Heparin