TY - JOUR
T1 - Time course characterization of serum cardiac troponins, heart fatty acid - Binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat
AU - Clements, Peter
AU - Brady, Sally
AU - York, Malcolm
AU - Berridge, Brian
AU - Mikaelian, Igor
AU - Nicklaus, Rosemary
AU - Gandhi, Mitul
AU - Roman, Ian
AU - Stamp, Clare
AU - Davies, Dai
AU - McGill, Paul
AU - Williams, Thomas
AU - Pettit, Syril
AU - Walker, Dana
AU - Turton, John
AU - Bounous, Denise
AU - Dunn, Bob
AU - Hausner, Elisabeth
AU - Herman, Eugene
AU - Holt, Gordon
AU - Lamb, Martin
AU - Louden, Calvert
AU - Mylecraine, Lou
AU - MacGregor, Jim
AU - Reagan, William
AU - Roome, Nigel
AU - Schultze, Eric
AU - Stoll, Ray
AU - Stonebrook, Mike
AU - Taggert, Peter
AU - Thudium, Doug
AU - Topper, Michael
AU - Wallace, Ken
PY - 2010/8
Y1 - 2010/8
N2 - We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 1/4g/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.
AB - We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 1/4g/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.
KW - cardiac troponin I
KW - cardiac troponin T
KW - cardiotoxicity
KW - heart fatty acid-binding protein
KW - immunohistochemistry
KW - rat
KW - ultrastructure
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U2 - 10.1177/0192623310374969
DO - 10.1177/0192623310374969
M3 - Article
C2 - 20585145
AN - SCOPUS:77958573514
SN - 0192-6233
VL - 38
SP - 703
EP - 714
JO - Toxicologic Pathology
JF - Toxicologic Pathology
IS - 5
ER -