title: Baseline serum cardiac troponin I concentrations in Sprague-Dawley, spontaneous hypertensive, Wistar, Wistar-Kyoto, and Fisher rats as determined with an ultrasensitive immunoassay.
abstract: Cardiac troponins have proved to be reliable blood biomarkers for identifying a variety of myocardial alterations in humans and animals. Recently, an ultrasensitive cTnI assay (Erenna IA) has been used to demonstrate increases in baseline cTnI resulting from drug-induced myocardial injury in rats, dogs, and monkeys, as well as to document baseline cTnI ranges in Sprague-Dawley (SD) rats. The present study was initiated to use the Erenna cTnI assay to further document baseline cTnI concentrations in normal control animals from multiple strains, including SD, Spontaneous Hypertensive (SHR), Wistar, Wistar-Kyoto (WKY), and Fisher strains. Baseline cTnI concentrations were quantified in all rats tested, and males had higher mean cTnI concentrations than females of the same strain. SHR males had the highest mean cTnI concentrations and the largest cTnI variability. Interestingly, cTnI concentrations increased in castrated SHR compared with unaltered male SHR, whereas cTnI concentrations decreased in ovariectomized SHR compared with unaltered female SHR. These results show significant differences in cTnI concentrations between strains, sexes, and noncardiac surgical alterations in control animals, and identify these as potential contributing factors to cTnI baseline variability that should be taken into account when using ultrasensitive cTnI as a biomarker to assess preclinical cardiotoxicity.
authors.affiliation: Division of Applied Pharmacology Research, Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. Eugene.Herman@fda.hhs.gov
authors.forename: Eugene
authors.initials: E
authors.lastname: Herman
authors.forename: Alan
authors.initials: A
authors.lastname: Knapton
authors.forename: Elliot
authors.initials: E
authors.lastname: Rosen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Joel
authors.initials: J
authors.lastname: Estis
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Agee
authors.forename: Quynh-Anh
authors.initials: QA
authors.lastname: Lu
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
mesh_terms: D000818:Animals; D000830:Animals, Laboratory / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006321:Heart / Q000187:drug effects; D006335:Heart Injuries / Q000139:chemically induced / Q000473:pathology; D007118:Immunoassay / Q000379:methods*; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344 / Q000097:blood; D011918:Rats, Inbred SHR / Q000097:blood; D011921:Rats, Inbred WKY / Q000097:blood; D017207:Rats, Sprague-Dawley / Q000097:blood; D017208:Rats, Wistar / Q000097:blood; D012737:Sex Factors; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I