title: Ultrasensitive cross-species measurement of cardiac troponin-I using the Erenna immunoassay system.
abstract: Serum cardiac troponin-I (cTnI) has been validated as a biomarker for cardiotoxicity in numerous animal models; however, owing to sensitivity issues cTnI concentrations in healthy, resting animals used in toxicology studies have not been established. Serum from healthy and isoproterenol hydrochloride (iso)-treated rats, dogs, and monkeys were assayed using the Erenna system. The Erenna cTnI assay provided sensitivity < 1 ng/L across human, rat, dog, and monkey cTnI. Linear responses (R(2)= 0.99) were observed for all species. Precision studies yielded interassay CVs of curve fit quantification from 2% to 4% between 1.6 and 5000 ng/L, and 23% at 0.78 ng/L. Strong correlation (R(2)= 0.99) was obtained between Erenna and Beckman Access cTnI. Concentrations of cTnI in healthy animals ranged from 1 to 9 ng/L. In longitudinal studies of iso-treated animals, the concentrations of cTnI in the control vehicle-treated groups were 10-20 ng/L for rats (N = 10) and predose values of 2-3 ng/L for dogs (N = 3). Measured with the Erenna assay system, cTnI was quantifiable at all time intervals tested in all animals treated with iso. The Erenna system provides sensitive measurement of cTnI in rats, dogs, and monkeys, makes it possible to determine small changes from normal concentrations, and provides cTnI values from small volumes of serum.
authors.affiliation: Department of Pathology, Lilly Research Laboratories, Greenfield, Indiana 46140, USA. aes@lilly.com
authors.forename: A Eric
authors.initials: AE
authors.lastname: Schultze
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Konrad
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Credille
authors.forename: Quynh Anh
authors.initials: QA
authors.lastname: Lu
authors.forename: John
authors.initials: J
authors.lastname: Todd
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004285:Dogs; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007545:Isoproterenol / Q000494:pharmacology; D016014:Linear Models; D008252:Macaca fascicularis; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I; D007545:Isoproterenol