Toxicologic Pathology

 

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First published on July 22, 2008
Toxicologic Pathology 2008, doi:10.1177/0192623308322016

Article

Ultrasensitive Cross-species Measurement of Cardiac Troponin-I Using the Erenna Immunoassay System

A. Eric Schultze DVM, PhD, DACVP*, Robert J. Konrad, Kelly M. Credille, Quynh Anh Lu, and John Todd

* To whom correspondence should be addressed. E-mail: aes{at}lilly.com.


  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 (R2 =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 (R2 = 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.


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