title: Pathological and Clinical Analysis of Vascular Catheterization Models in Rats, with Exploration of Interventions to Improve Clinical Tolerance.
abstract: Permanent vascular catheterization for intravascular access is one of the most commonly applied techniques used on rodents in pharmacology studies. However, use of the intravascular catheters is complicated by nontolerance due to thromboembolic disease and sepsis. We have undertaken an extensive pathologic and clinical analysis of an intravascular catheterization model in Wistar Han and Sprague-Dawley rats, with a particular focus on carotid artery catheterization with or without jugular vein catheterization, in order to define the pathologic mechanisms behind nontolerance and define clinical end points to ensure maximal animal welfare. Further, we have explored various potential solutions to increase the tolerance of the procedure. In these studies, indwelling catheters were found to cause a high degree of thromboembolic disease with infarction in the brain, cecal tip, and kidneys being the primary causes of nontolerance. Loss of greater than 10% body weight was determined to be the most sensitive indicator of nontolerance and was closely correlated with degree of renal parenchymal loss. Sepsis was noted as a very rare complication, indicating that routine aseptic surgical techniques are adequate for preventing this complication.
authors.affiliation: 1 Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, United Kingdom.|2 School of Veterinary Science, University of Queensland Gatton Campus, Gatton, Queensland, Australia.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Allavena
authors.affiliation: 1 Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, United Kingdom.|3 West Heather, Kent, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: West
authors.affiliation: 1 Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gale
authors.affiliation: 1 Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, United Kingdom.|4 Pfizer Kendall Square, Cambridge, Massachusetts, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Debrue
mesh_terms: D000827:Animal Welfare; D000818:Animals; D001800:Blood Specimen Collection / Q000009:adverse effects* / Q000295:instrumentation; D002339:Carotid Arteries / Q000601:surgery; D002404:Catheterization / Q000009:adverse effects* / Q000295:instrumentation; D002408:Catheters, Indwelling / Q000009:adverse effects; D007601:Jugular Veins / Q000601:surgery; D023421:Models, Animal; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013923:Thromboembolism / Q000209:etiology*
keywords: animal models; intravascular catheterization models; preclinical safety assessment; rat pathology; welfare