title: Characterization of troponin responses in isoproterenol-induced cardiac injury in the Hanover Wistar rat.
abstract: The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute myocardial injury in the rat. Serum from female Hanover Wistar rats treated with a single intraperitoneal (IP) injection of isoproterenol (ISO) was assayed for cardiac troponin I (cTnI) (ACS: 180SE, Bayer), cTnI (Immulite 2000, Diagnostic Products Corporation) and cardiac troponin T (cTnT) (Elecsys 2010, Roche). In a time-course study (50.0 mg/kg ISO), serum cTnI (ACS:180SE) and cTnT increased above control levels at 1 hour postdosing, peaking at 2 hours (cTnI, 4.30 microg/L; cTnT, 1.79 microg/L), and declined to baseline by 48 hours, with histologic cardiac lesions first seen at 4 hours postdosing. The Immulite 2000 assay gave minimal cTnI signals, indicating poor immunoreactivity towards rat cTnI. In a dose-response study (0.25 to 20.0 mg/kg ISO), there was a trend for increasing cTnI (ACS:180SE) values with increasing ISO dose levels at 2 hours postdosing. By 24 hours, cTnI levels returned to baseline although chronic cardiac myodegeneration was present. We conclude that serum cTnI and cTnT levels are sensitive and specific biomarkers for detecting ISO induced myocardial injury in the rat. Serum troponin values reflect the development of histopathologic lesions; however peak troponin levels precede maximal lesion severity.
authors.affiliation: GlaxoSmithKline Research and Development, Ware, Herts, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: York
authors.forename: Cheryl
authors.initials: C
authors.lastname: Scudamore
authors.forename: Sally
authors.initials: S
authors.lastname: Brady
authors.forename: Christabelle
authors.initials: C
authors.lastname: Chen
authors.forename: Sharon
authors.initials: S
authors.lastname: Wilson
authors.forename: Mark
authors.initials: M
authors.lastname: Curtis
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: William
authors.initials: W
authors.lastname: Griffiths
authors.forename: Matthew
authors.initials: M
authors.lastname: Whayman
authors.forename: Thomas
authors.initials: T
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Turton
mesh_terms: D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014336:Troponin / Q000097:blood / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D007527:Isoenzymes; D014336:Troponin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D007545:Isoproterenol