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Received on September 13, 2007
Accepted on August 26, 2008
Animal Clinical Chemistry |
1 Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and the University of Minnesota School of Medicine, Minneapolis, MN
2 Bristol-Myers Squibb, Ware, Herfordshire, UK
3 GlaxoSmithKline R&D, Ware, Herfordshire, UK, and ILSI Heath and Environmental Sciences Institute, Washington DC, USA
4 Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and the University of Minnesota School of Medicine, Minneapolis, MN, and Bristol-Myers Squibb, Ware, Herfordshire, UK, and GlaxoSmithKline R&D, Ware, Herfordshire, UK, and ILSI Heath and Environmental Sciences Institute, Washington DC, USA
* To whom correspondence should be addressed. E-mail: apple04{at}umn.edu.
BACKGROUND: Information is needed regarding analytical characteristics of cardiac troponin (cTn) assays used in preclinical studies.
METHODS: We measured cTnI and cTnT in serum from normal animals and animals with induced myocardial injury [Sprague–Dawley (SD) and Wistar rats, beagle dogs, and rhesus (Rh) and cynomolgus (Cy) monkeys]. We evaluated the following assays: for cTnI, Abbott Architect, Bayer Centaur (first and second generation), Beckman Access, DPC Immulite, Dade Dimension, Ortho Vitros ES, Tosoh AIA, and species-specific enzyme immunoassays; for cTnT, Roche Elecsys.
RESULTS: We found different species-specific responses for the troponin assays evaluated. Abbott, Bayer Ultra, Beckman, and Dade assays gave good responses across all species. In rats, weak responses were observed with DPC and Ortho, and no measurable response with Tosoh. In dogs, weak responses were observed with Tosoh cTnI, Roche cTnT, and species-specific cTnI. In cynomolgus monkeys, weak responses were observed with species-specific cTnI and Roche cTnT. Assay imprecision was 
20% at 3 or more examined cTn concentrations for Beckman (rat, dog, monkey), Dade (rat, dog, monkey), Abbott (rat, dog, monkey), Bayer first generation (dog), Bayer Ultra (rat, dog, monkey), Roche (monkey), DPC (dog, monkey), Ortho (dog, monkey), and Tosoh (dog, monkey) assays, whereas imprecision was 20% at 2 or fewer concentrations for the Bayer first generation (rat, monkey), Roche cTnT (rat, dog), and DPC (rat) assays.
CONCLUSIONS: Not all cTn assays are suitable for monitoring cTn in each animal species or strain. Individual assay characterization by animal species is needed to prevent misinterpretation of myocardial injury–based cardiac troponin findings.
The following articles in journals at HighWire Press have cited this article:
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  A. E. Schultze, K. H. Carpenter, F. H. Wians, S. J. Agee, J. Minyard, Q. A. Lu, J. Todd, and R. J. Konrad Longitudinal Studies of Cardiac Troponin-I Concentrations in Serum from Male Sprague Dawley Rats: Baseline Reference Ranges and Effects of Handling and Placebo Dosing on Biological Variability Toxicol Pathol, October 1, 2009; 37(6): 754 - 760. [Abstract] [Full Text] [PDF]
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S. K. Engle, W. H. Jordan, M. L. Pritt, A. Y. Chiang, M. A. Davis, J. L. Zimmermann, D. G. Rudmann, K. M. Heinz-Taheny, A. R. Irizarry, Y. Yamamoto, et al. Qualification of Cardiac Troponin I Concentration in Mouse Serum Using Isoproterenol and Implementation in Pharmacology Studies to Accelerate Drug Development Toxicol Pathol, August 1, 2009; 37(5): 617 - 628. [Abstract] [Full Text] [PDF]
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