Serum cardiac troponin T as a biomarker for acute myocardial injury induced by low doses of isoproterenol in rats.
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 Iso also cause cardiac alterations and whether monitoring cTnT levels could detect this injury. Rats received 8 to 500 microg/kg Iso 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 microg/kg Iso (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 microg/kg Iso. Doses of 125, 250, or 500 microg/kg Iso 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 Iso 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.
Herman
Eugene
E
Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA. eugene.herman@fda.hhs.gov
Zhang
Jun
J
Knapton
Alan
A
Lipshultz
Steven E
SE
Rifai
Nader
N
Sistare
Frank
F
D000208:Acute Disease; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood* / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020107:Troponin T / Q000097:blood* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D020107:Troponin T; D007545:Isoproterenol