title: Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals.
abstract: This study directly demonstrates that cardiac troponin I (cTnI) is a sensitive, specific, and persistent biomarker in laboratory animals. Histopathological and pathophysiological cardiac changes in dogs, rats and mice correlated with increased serum cTnI with various cardiac inotropic agents, and cardiotoxic drugs and with cardiac arrhythmias, tachycardia, cardiac effusion with dyspnoea, and ageing. A comparison of six immunoassays for cTnI and cardiac troponin T (cTnT) to detect and monitor cardiac injury in a rodent model indicated that enzyme-linked immunosorbent (Life Diagnostics Inc and TriChem Resources Inc, West Chester, Philadelphia, USA) and Immulite (Diagnostic Products Corporation, Llanberis, UK) assays had low sensitivity and less than 1% of the dynamic range of Centaur (Bayer Healthcare Diagnostics, Newbury, UK) cTnI and Elecsys (Roche Diagnostics, Basel, Switzerland) and M8 (Bioveris Europe, Whitney, UK) cTnT assays. In dogs, however, the Immulite assay was effective and correlated with the Centaur. Serum concentrations were highly correlated but 10-fold lower for cTnT compared with cTnI with cardiac injury. Centaur assay also detected cTnI in myocardium from marmosets, swine, cattle, and guinea pigs, indicating it to be candidate cardiac biomarker for these species as well. Purified rat cTnI was 50% more reactive than purified human cTnI in the Centaur assay. In the rat, an age- and gender-dependent variation in serum cTnI was found. Male rats aged six and eight months had a 10-fold greater serum cTnI than age-matched females and three-month-old rats. These increases correlated with minimal histopathological change. Isoproterenol-induced serum cTnI increased up to 760-fold the minimal detectable concentration of 0.07 microg/L, within 4-6 h and decreased with a half-life of 6 h, with an expected return to baseline of 60 h. Severity of histopathological change correlated with serum cTnI during the ongoing injury.
authors.affiliation: Safety Sciences Europe, Sandwich, Kent CT1 3NJ, UK. Peter.O'Brien@pfizer.com
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Brien
authors.forename: D E C
authors.initials: DE
authors.lastname: Smith
authors.forename: T J
authors.initials: TJ
authors.lastname: Knechtel
authors.forename: M A
authors.initials: MA
authors.lastname: Marchak
authors.forename: I
authors.initials: I
authors.lastname: Pruimboom-Brees
authors.forename: D J
authors.initials: DJ
authors.lastname: Brees
authors.forename: D P
authors.initials: DP
authors.lastname: Spratt
authors.forename: F J
authors.initials: FJ
authors.lastname: Archer
authors.forename: P
authors.initials: P
authors.lastname: Butler
authors.forename: A N
authors.initials: AN
authors.lastname: Potter
authors.forename: J P
authors.initials: JP
authors.lastname: Provost
authors.forename: J
authors.initials: J
authors.lastname: Richard
authors.forename: P A
authors.initials: PA
authors.lastname: Snyder
authors.forename: W J
authors.initials: WJ
authors.lastname: Reagan
mesh_terms: D000820:Animal Diseases / Q000097:blood* / Q000175:diagnosis; D000818:Animals; D000830:Animals, Laboratory / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004285:Dogs; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000662:veterinary*; D008163:Luminescent Measurements / Q000592:standards / Q000662:veterinary*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T