TY - JOUR
T1 - Molecular Imaging for Efficacy of Pharmacologic Intervention in Myocardial Remodeling
AU - van den Borne, Susanne W.M.
AU - Isobe, Satoshi
AU - Zandbergen, H. Reinier
AU - Li, Peng
AU - Petrov, Artiom
AU - Wong, Nathan D.
AU - Fujimoto, Shinichiro
AU - Fujimoto, Ai
AU - Lovhaug, Dagfinn
AU - Smits, Jos F.M.
AU - Daemen, Mat J.A.P.
AU - Blankesteijn, W. Matthijs
AU - Reutelingsperger, Chris
AU - Zannad, Faiez
AU - Narula, Navneet
AU - Vannan, Mani A.
AU - Pitt, Bertram
AU - Hofstra, Leonard
AU - Narula, Jagat
N1 - Funding Information:
Dr. van den Borne was partially supported by a grant from the Netherlands Heart Foundation (2006R013). Dr. Lovhaug is an employee of GE Healthcare, involved in tracer preparation for the imaging studies. Dr. Pitt is a consultant to Pfizer, Merck, Takeda, Astra Zeneca, Synvista, Novartis, and Nile therapeutics but has no conflicts directly with the project. H. William Strauss, MD, acted as Guest Editor for this paper.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - angiotensin receptors
KW - angiotensin-converting enzyme
KW - collagen
KW - heart failure
KW - mineralocorticoids
KW - radionuclide imaging
KW - remodeling
UR - https://www.scopus.com/pages/publications/59649126215
U2 - 10.1016/j.jcmg.2008.11.011
DO - 10.1016/j.jcmg.2008.11.011
M3 - Article
C2 - 19356555
AN - SCOPUS:59649126215
SN - 1936-878X
VL - 2
SP - 187
EP - 198
JO - JACC: Cardiovascular Imaging
JF - JACC: Cardiovascular Imaging
IS - 2
ER -