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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.

AbstractBACKGROUND:
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.
AuthorsPetra Lynch, Te-Chung Lee, James A Fallavollita, John M Canty Jr, Gen Suzuki
JournalCirculation (Circulation) Vol. 116 Issue 11 Suppl Pg. I71-6 (Sep 11 2007) ISSN: 1524-4539 [Electronic] United States
PMID17846328 (Publication 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.)
Chemical References
  • Fibroblast Growth Factor 5
Topics
  • 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)

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