Spontaneous findings in the heart of Mauritian-origin cynomolgus macaques (Macaca fascicularis).
The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but the impact of the geographic source of cynomolgus macaque on differences in spontaneous pathology and response to xenobiotics has only recently been explored. Previous work from the authors' facility has described spontaneous cardiac findings in predominantly Indonesian-source animals; however, the authors have recently observed a novel spectrum of cardiac findings in Mauritian-source animals. This review evaluated the spontaneous macroscopic and microscopic cardiac findings in vehicle control Mauritian-source macaques used for routine toxicity testing. When compared to the prior review in predominantly Indonesian macaques, a higher incidence of myocardial degeneration was observed with additional novel findings including macroscopic and microscopic subendocardial hemorrhage with hemosiderin, myocardial fibrosis, and arterial medial degeneration/hemorrhage. Other findings including inflammatory cell infiltrates, anisokaryosis, and squamous plaques were observed with a comparable incidence as previously reported in Indonesian macaques. Myocardial degeneration, subendocardial hemorrhage, and myocardial fibrosis can mimic test-article-related cardiac toxicity, and a thorough understanding of the incidence and severity of these spontaneous findings is necessary to prevent misidentifying test-article-related cardiac findings in this genetic source of cynomolgus macaque in nonclinical safety testing.
Vidal
Justin D
JD
GlaxoSmithKline, King of Prussia, PA 19406-0939, USA. justin.2.vidal@gsk.com
Drobatz
Lita S
LS
Holliday
Denise F
DF
Geiger
Lee E
LE
Thomas
Heath C
HC
D000818:Animals; D005260:Female; D005843:Geography; D006331:Heart Diseases / Q000473:pathology / Q000662:veterinary*; D008252:Macaca fascicularis; D008297:Male; D008435:Mauritania; D008436:Mauritius; D008992:Monkey Diseases / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D018675:Toxicity Tests