Assessment of the toxicity of hydralazine in the rat using an ultrasensitive flow-based cardiac troponin I immunoassay.
The purpose of this study was to correlate the histologic changes in the heart to serum cardiac troponin I (cTnI) concentrations assayed with the Erenna Immunoassay System in Wistar rats (Crl:Wi[Han]) using the hydralazine model of cardiotoxicity. A single dose of hydralazine caused an increase of cTnI concentrations at six hours post-dose, followed by a sharp decrease at twenty-four hours and a return to baseline at forty-eight hours. The second dose of hydralazine caused a smaller magnitude increase in cTnI concentrations at six hours as compared to the first dose. Also, cTnI concentrations returned to baseline at twenty-four hours after the second dose. The increased cTnI concentrations coincided with acute myocardial necrosis at histology. However, increased cTnI concentrations in the absence of microscopic lesions were identified in several rats. As cTnI concentrations decreased, microscopic changes in the heart matured to cardiomyophagy. In conclusion, the increases in cTnI concentrations six hours after the administration of hydralazine were indicative of a myocardial damage that did not consistently have a microscopic correlate. However, the window of increased cTnI concentrations was short, and only microscopic evaluation of the heart detected the damage at twenty-four to forty-eight hours after the episode of acute myocardial necrosis.
Mikaelian
Igor
I
Non-Clinical Safety, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA. igor.mikaelian@roche.com
Coluccio
Denise
D
Hirkaler
Gerard M
GM
Downing
John C
JC
Rasmussen
Erik
E
Todd
John
J
Estis
Joel
J
Lu
Quynh Anh
QA
Nicklaus
Rosemary
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006830:Hydralazine / Q000633:toxicity*; D007118:Immunoassay / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D018675:Toxicity Tests; D019210:Troponin I / Q000378:metabolism*
D019210:Troponin I; D006830:Hydralazine