Article

Cardiovascular Toxicology

, Volume 6, Issue 3, pp 211-221

First online:

Serum cardiac troponin T as a biomarker for acute myocardial injury induced by low doses of isoproterenol in rats

  • Eugene HermanAffiliated withDivision of Applied Pharmacology Research (HFD-910), Center for Drug Evaluation and Research Fod and Drug Administration Email author 
  • , Jun ZhangAffiliated withDivision of Applied Pharmacology Research (HFD-910), Center for Drug Evaluation and Research Fod and Drug Administration
  • , Alan KnaptonAffiliated withDivision of Applied Pharmacology Research (HFD-910), Center for Drug Evaluation and Research Fod and Drug Administration
  • , Steven E. LipshultzAffiliated withDepartment of Pediatrics, University of MiamiMiller School of Medicine
  • , Nader RifaiAffiliated withChildren's Hospital, Harvard Medical School
  • , Frank SistareAffiliated withDivision of Applied Pharmacology Research (HFD-910), Center for Drug Evaluation and Research Fod and Drug AdministrationMerck Research Labs

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Abstract

In rats, high doses of isoproterenol (Iso) have caused acute myocardial lesions and increased serum levels of cardiac troponin T (cTnT). We determined whether low doses of lso also cause cardiac alterations and whether monitoring cTnT levels could detect this injury. Rats received 8 to 500 μg/kg lso and were followed for 3 to 48 h. Lesion severity was scored from 0 to 5. Within 3 h, mean cTnT was elevated in all 29 rats receiving 8, 16, 32, or 64 μg/kg lso (0.20 to 0.28 ng/mL), but minimal lesions occurred in only two animals. However, by 6 h, cardiac lesions and increases in serum cTnT (mean=0.21 to 0.23 ng/mL) were observed in all 14 rats receiving 32 or 64 μg/kg lso. Doses of 125, 250, or 500 μg/kg lso caused more significant increases in cTnT levels and marked myocardial lesions that reached a peak 3 to 6 h after dosing. The magnitude of the lesions and cTnT levels declined between 12 and 48 h post treatment. Thus, a range of low lso doses can cause myocardial lesions, and serum cTnT levels can be monitored to detect the onset and progression of this type of acute cardiac injury in rats; however, careful attention to dosing and sampling times is critical to interpretation.

Index Entries

Cardiac troponin T isoproterenol myocardial damage low dose