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.
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.


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).


CONCLUSIONS
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.
Lynch
Petra
P
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, NY 14214, USA.
Lee
Te-Chung
TC
Fallavollita
James A
JA
Canty
John M
JM
Suzuki
Gen
G
D000818:Animals; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D051521:Fibroblast Growth Factor 5 / Q000008:administration & dosage*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D051521:Fibroblast Growth Factor 5