Time course characterization of serum cardiac troponins, heart fatty acid - Binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat

Peter Clements, Sally Brady, Malcolm York, Brian Berridge, Igor Mikaelian, Rosemary Nicklaus, Mitul Gandhi, Ian Roman, Clare Stamp, Dai Davies, Paul McGill, Thomas Williams, Syril Pettit, Dana Walker, John Turton, Denise Bounous, Bob Dunn, Elisabeth Hausner, Eugene Herman, Gordon HoltMartin Lamb, Calvert Louden, Lou Mylecraine, Jim MacGregor, William Reagan, Nigel Roome, Eric Schultze, Ray Stoll, Mike Stonebrook, Peter Taggert, Doug Thudium, Michael Topper, Ken Wallace

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)703-714
Number of pages12
JournalToxicologic Pathology
Volume38
Issue number5
DOIs
StatePublished - Aug 2010

Keywords

  • cardiac troponin I
  • cardiac troponin T
  • cardiotoxicity
  • heart fatty acid-binding protein
  • immunohistochemistry
  • rat
  • ultrastructure

Fingerprint

Dive into the research topics of 'Time course characterization of serum cardiac troponins, heart fatty acid - Binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat'. Together they form a unique fingerprint.

Cite this