Spontaneous cardiomyopathy in young Sprague-Dawley rats: evaluation of biological and environmental variability.

Abstract:

:Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations in the normal heart histology. It is therefore crucial to understand the normal variations in histology to discriminate test article-related changes from background lesions. Rodent progressive cardiomyopathy is probably the most commonly encountered change in control animals of nonclinical toxicity studies. A multisite study mimicking standard short-term toxicity studies using young male Sprague-Dawley rats was performed to better characterize this finding. Using an enhanced sectioning method for this research study, it was observed that the incidence of background cardiomyopathy was 100%. The vast majority of the microscopic findings were inflammatory in nature, with associated necrotic changes (defined as necrosis/inflammatory cell infiltrate) and these changes were mainly located in the myocardium of the mid region of the ventricles (the left side being predominantly affected). The monitored environmental factors in this study (multiple facilities, study duration, handling) did not have an effect on the incidence or severity of the spontaneous cardiomyopathy. In addition, cardiac-specific serum troponin levels were measured and were within the published control range.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Chanut F,Kimbrough C,Hailey R,Berridge B,Hughes-Earle A,Davies R,Roland K,Stokes A,Casartelli A,York M,Jordan H,Crivellente F,Cristofori P,Thomas H,Klapwijk J,Adler R

doi

10.1177/0192623313478692

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

1126-36

issue

8

eissn

0192-6233

issn

1533-1601

pii

0192623313478692

journal_volume

41

pub_type

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