Document Detail


Intracoronary administration of AdvFGF-5 (fibroblast growth factor-5) ameliorates left ventricular dysfunction and prevents myocyte loss in swine with developing collaterals and ischemic cardiomyopathy.
MedLine Citation:
PMID:  17846328     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Fibroblast growth factor (AdvFGF-5) improves regional function by stimulating myocyte hypertrophy without increasing myocardial perfusion in swine with hibernating myocardium. We performed the present study to determine whether AdvFGF-5 could prevent the progression of LV dysfunction in swine with ischemic cardiomyopathy. METHODS AND RESULTS: Swine were chronically instrumented with LAD and LCX stenoses to produce viable dysfunctional myocardium and studied 1 month after instrumentation in the closed-chest sedated state. Flow and regional function before and 30 days after intracoronary AdvFGF-5 (2x10(12) vp, n=9) were compared with animals receiving intracoronary AdvEGFP (2x10(12) vp, n=6). Histological analysis was performed to quantify myocyte size, myocyte nuclear density, apoptosis (TUNEL), and the frequency of myocytes in the proliferative phase of the cell cycle (Ki-67 staining). LAD wall-thickening (27+/-3 to 46+/-6%, P<0.05) and EF (39+/-4 to 56+/-3%, P<0.05) increased after AdvFGF-5. AdvFGF-5 increased maximal perfusion during adenosine vasodilation despite no differences in baseline flow or stenosis severity. After AdvFGF-5, TUNEL-positive myocytes decreased 6-fold and Ki-67 positive myocyte nuclei increased 2-fold. As a result, AdvFGF-5 produced a marked increase in myocyte nuclear density (957+/-54 to 1447+/-40 nuclei/mm2, P<0.05). CONCLUSION: These data indicate that AdvFGF-5 increases regional function and maximal perfusion distal to stenotic arteries when administered before the development of collaterals. This was associated with a reduction in myocyte apoptosis, an increase in Ki-67-positive myocytes, and an increase in myocyte number. Thus, AdvFGF-5 offers a potential therapeutic approach to prevent the progression of ischemic cardiomyopathy and heart failure.
Authors:
Petra Lynch; Te-Chung Lee; James A Fallavollita; John M Canty; Gen Suzuki
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-11     Completed Date:  2007-10-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  I71-6     Citation Subset:  AIM; IM    
Affiliation:
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, NY 14214, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomyopathies / complications,  drug therapy*,  physiopathology
Collateral Circulation / drug effects,  physiology
Fibroblast Growth Factor 5 / administration & dosage*
Myocardial Ischemia / complications,  drug therapy*,  physiopathology
Myocytes, Cardiac
Neovascularization, Physiologic / drug effects*,  physiology
Swine
Ventricular Dysfunction, Left / complications,  drug therapy*,  physiopathology
Chemical
Reg. No./Substance:
129653-64-1/Fibroblast Growth Factor 5

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


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