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Endocardial Myxomatous Change in Harlan Sprague-Dawley Rats (Hsd:S—D) and CD-1 Mice: Its Microscopic Resemblance to Drug-Induced Valvulopathy in Humans

Department of Pathology, GlaxoSmithKline Inc, Research Triangle Park, North Carolina, USA, cse63957{at}gsk.com

Karyn A. Colman

Department of Pathology, ClinTrialsBioResearch (CTBR) Ltd, Quebec, Canada

Ruth M. Lightfoot

Department of Safety Assessment, GlaxoSmithKline Inc, Research Triangle Park, North Carolina, USA

Ronald D. Tyler

Department of Safety Assessment, GlaxoSmithKline Inc, Research Triangle Park, North Carolina, USA

Henry G. Wall

Department of Pathology, GlaxoSmithKline Inc, Research Triangle Park, North Carolina, USA

A full assessment of all heart valves in rats and mice is often impractical and is usually not performed in routine toxicity studies, largely due to an inevitable inconsistency of histological sampling. The majority of reported heart valve changes involve the examination of a single, semirandom section through the heart and the valvulopathy occurring with age or induced by xenobiotics may have been generally underestimated in mice and rats. Here we describe the incidence and microscopic features of endocardial myxomatous change (EMC) in Hsd:S—D rats and CD-1 mice. EMC was common and widespread in both CD-1 mice and Hsd:S—D rats (188 of 220 rats and 96 of 215 mice were affected by EMC). Microscopically, EMC consisted of focal or segmental thickening of valves, primarily due to the presence of fibromyxoid tissue in the subendocardium. Occasionally, fibrin or thrombi deposits and collection of neutrophils or mononuclear cells were observed. These microscopic features were similar to those seen in valvular disease in humans induced by fenfluramine-phentermine (fen-phen), ergot alkaloids (ergotamine, methysergide), and carcinoid syndrome. The mitral valve in rats and pulmonary valve in mice were most frequently affected. An association between murine progressive cardiomyopathy (MPC) and EMC was noted only in rats, suggesting that there may be a possible relationship between MPC and EMC. However, additional research is needed to confirm a relationship between EMC and MPC in rats and/or mice.

Key Words: Endocardial myxomatous change • age-related • Sprague-Dawley rats • CD-1 mice • valvular disease • atrial thrombosis • murine progressive cardiomyopathy.

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Toxicologic Pathology, Vol. 30, No. 4, 483-491 (2002)
DOI: 10.1080/01926230290105703


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