Document Detail


Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.
MedLine Citation:
PMID:  20585145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 microg/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.
Authors:
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
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Publication Detail:
Type:  Journal Article     Date:  2010-06-28
Journal Detail:
Title:  Toxicologic pathology     Volume:  38     ISSN:  1533-1601     ISO Abbreviation:  Toxicol Pathol     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2011-01-03     Revised Date:  2012-01-05    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  703-14     Citation Subset:  IM    
Affiliation:
GlaxoSmithKline, Safety Assessment Pathology, Hertfordshire, UK. peter.j.clements@gsk.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / blood*
Cardiotonic Agents / toxicity
Fatty Acid-Binding Proteins / blood*
Heart / drug effects
Heart Injuries / blood*,  pathology*
Immunoassay
Isoproterenol / toxicity
Luminescence
Male
Microscopy, Electron, Transmission
Myocardium / pathology*
Myocytes, Cardiac / drug effects,  pathology
Rats
Rats, Wistar
Sensitivity and Specificity
Time
Troponin / blood*
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cardiotonic Agents; 0/Fatty Acid-Binding Proteins; 0/Troponin; 7683-59-2/Isoproterenol
Investigator
Investigator/Affiliation:
Brian Berridge / ; Denise Bounous / ; Bob Dunn / ; Elisabeth Hausner / ; Eugene Herman / ; Gordon Holt / ; Martin Lamb / ; Calvert Louden / ; Lou Mylecraine / ; Rosemary Nicklaus / ; Jim MacGregor / ; Syril Pettit / ; William Reagan / ; Nigel Roome / ; Eric Schultze / ; Ray Stoll / ; Mike Stonebrook / ; Peter Taggert / ; Doug Thudium / ; Michael Topper / ; Dana Walker / ; Ken Wallace / ; Malcolm York /

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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