Document Detail

Molecular imaging for efficacy of pharmacologic intervention in myocardial remodeling.
MedLine Citation:
PMID:  19356555     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Using molecular imaging techniques, we examined interstitial alterations during postmyocardial infarction (MI) remodeling and assessed the efficacy of antiangiotensin and antimineralocorticoid intervention, alone and in combination. BACKGROUND: The antagonists of the renin-angiotensin-aldosterone axis restrict myocardial fibrosis and cardiac remodeling after MI and contribute to improved survival. Radionuclide imaging with technetium-99m-labeled Cy5.5 RGD imaging peptide (CRIP) targets myofibroblasts and indirectly allows monitoring of the extent of collagen deposition post-MI. METHODS: CRIP was intravenously administered for gamma imaging after 4 weeks of MI in 63 Swiss-Webster mice and in 6 unmanipulated mice. Of 63 animals, 50 were treated with captopril (C), losartan (L), spironolactone (S) alone, or in combination (CL, SC, SL, and SCL), 8 mice received no treatment. Echocardiography was performed for assessment of cardiac remodeling. Hearts were characterized histopathologically for the presence of myofibroblasts and thick and thin collagen fiber deposition. RESULTS: Acute MI size was similar in all groups. The quantitative CRIP percent injected dose per gram uptake was greatest in the infarct area of untreated control mice (2.30 +/- 0.14%) and decreased significantly in animals treated with 1 agent (C, L, or S; 1.71 +/- 0.35%; p = 0.0002). The addition of 2 (CL, SC, or SL 1.31 +/- 0.40%; p < 0.0001) or 3 agents (SCL; 1.16 +/- 0.26%; p < 0.0001) demonstrated further reduction in tracer uptake. The decrease in echocardiographic left ventricular function, strain and rotation parameters, as well as histologically verified deposition of thin collagen fibers, was significantly reduced in treatment groups and correlated with CRIP uptake. CONCLUSIONS: Radiolabeled CRIP allows for the evaluation of the efficacy of neurohumoral antagonists after MI and reconfirms superiority of combination therapy. If proven clinically, molecular imaging of the myocardial healing process may help plan an optimal treatment for patients susceptible to heart failure.
Susanne W M van den Borne; Satoshi Isobe; H Reinier Zandbergen; Peng Li; Artiom Petrov; Nathan D Wong; Shinichiro Fujimoto; Ai Fujimoto; Dagfinn Lovhaug; Jos F M Smits; Mat J A P Daemen; W Matthijs Blankesteijn; Chris Reutelingsperger; Faiez Zannad; Navneet Narula; Mani A Vannan; Bertram Pitt; Leonard Hofstra; Jagat Narula
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JACC. Cardiovascular imaging     Volume:  2     ISSN:  1876-7591     ISO Abbreviation:  JACC Cardiovasc Imaging     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-04-09     Completed Date:  2009-07-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101467978     Medline TA:  JACC Cardiovasc Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  187-98     Citation Subset:  IM    
Division of Cardiology and Department of Pathology, University of California Irvine School of Medicine, Irvine, CA 92697, USA.
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MeSH Terms
Aldosterone Antagonists / pharmacology*
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Captopril / pharmacology
Carbocyanines / diagnostic use
Cardiovascular Agents / pharmacology*
Disease Models, Animal
Drug Therapy, Combination
Fibrillar Collagens / metabolism
Fibroblasts / drug effects,  radionuclide imaging
Losartan / pharmacology
Myocardial Infarction / drug therapy*,  physiopathology,  radionuclide imaging
Myocardium / metabolism,  pathology*
Oligopeptides / diagnostic use
Predictive Value of Tests
Spironolactone / pharmacology
Technetium / diagnostic use
Tomography, Emission-Computed, Single-Photon*
Ventricular Function, Left / drug effects
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Aldosterone Antagonists; 0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/CY5.5 cyanine dye; 0/Carbocyanines; 0/Cardiovascular Agents; 0/Fibrillar Collagens; 0/Oligopeptides; 114798-26-4/Losartan; 52-01-7/Spironolactone; 62571-86-2/Captopril; 7440-26-8/Technetium; 99896-85-2/arginyl-glycyl-aspartic acid
Comment In:
JACC Cardiovasc Imaging. 2009 Feb;2(2):199-201   [PMID:  19356556 ]

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