Affiliation:
1. Department of Veterinary Pathology, University of Liverpool, Liverpool L69 3BX, United Kingdom
Abstract
Evaluation of induced arterial toxicity in safety assessment of drugs involves recognition of morphologic differences between groups of animals. In this organ system, as in all others, it is necessary to be familiar with the background pathology that can occur in control animals of the test species, since such lesion “noise” may complicate the evaluation of drug-related effects if naturally occurring diseases have morphologic features in common with those that can be produced by drugs. Background arterial lesions have been regarded as relatively unimportant in both the laboratory-maintained beagle and in the larger range of domesticated breeds of dog and few of these vascular lesions lead, per se, to functional organ compromise. At least this appears to be the case in young and middle-aged subjects, within the epidemiologic limits of data from veterinary medical centers where systematic and thorough necropsies are done and recorded. Arterial lesions are, however, not uncommon naturally occurring incidental necropsy findings in dogs; however, in most cases they are of uncertain functional significance. This presentation summarizes the main pathologic patterns of lesions that can affect arteries in dogs that are not used in safety evaluation studies. The main patterns can be classified as degenerative, proliferative, and inflammatory, although there is some overlap between these partly arbitrary designations. In some cases, etiopathogenesis of the arterial lesion is unclear; in others, there are clear associations with disease processes in other organ systems. Congenital vascular lesions and vascular components of congenital cardiac defects are excluded from consideration since such lesions are unlikely to occur in dog populations used in the safety assessment of drugs.
Subject
Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine
Cited by
11 articles.
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