Basic fibroblast growth factor induces myocardial hypertrophy following acute infarction in rats.
Basic fibroblast growth factor (bFGF) is a potent mitogen which induces growth of collateral vessels in ischaemic and infarcted myocardium. The effect of systemically administered bFGF on left ventricular (LV) function, myocardial hypertrophy and LV remodelling following acute myocardial infarction (MI) have not yet been fully investigated. Thirty Sprague-Dawley male rats were randomized to receive bFGF (0.5 mg) or rat albumin intraperitoneally for 1 week, beginning immediately after the induction of MI. Five animals served as controls and did not undergo any operation. Animals were killed 6 weeks after surgery and the hearts were perfused and fixed at physiological pressure. Transverse cross-sections from infarcted areas were stained with antibodies against proliferating cell nuclear antigen (PCNA) and Masson-trichrome and analysed with a coloured-image analyser for LV area (mm2), LV cavity diameter (mm), infarcted area (%), and wall thickness (mm) in infarcted and non-infarcted regions. LV area was similar in MI rats and in controls (41.7 +/- 6.9 and 43.0 +/- 1.5 mm2, respectively) and was significantly larger in MI bFGF-treated (MI/bFGF) animals (47.6 +/- 7.1 mm2) (P = 0.023). LV cavity diameter was significantly larger in the MI group than in MI/bFGF and control animals (6.0 +/- 0.8, 4.9 +/- 1.4, and 4.4 +/- 0.8 mm, respectively, P = 0.018). Wall thickness in the non-infarcted region was significantly smaller in MI animals (1.4 +/- 0.3 mm) than in MI/bFGF animals (1.6 +/- 0.4 mm) and the control group (1.6 +/- 0.1 mm) (P = 0.015). The ratio between LV cavity diameter/non-MI wall thickness was higher in MI than in control and MI/bFGF groups (4.8 +/- 1.6, 2.7 +/- 0.6 and 3.3 +/- 1.8, respectively, P = 0.03). Proliferating endothelial cells were significantly more abundant in infarcted than in normal areas in both MI and MI/bFGF groups, but with no significant differences between the groups. Intraperitoneal administration of bFGF did not cause any untoward extracardiac effects. Thus, systemic bFGF administration following acute MI in rats prevents dilatation of the LV, induces hypertrophy of the non-infarcted myocardium and exerts no untoward effects on extracardiac organs.
Scheinowitz
M
M
Neufeld Cardiac Research Institute, Department of Biomedical Engineering, Tel Aviv University, Israel. mickeys@post.tau.ac.il
Kotlyar
A
A
Zimand
S
S
Ohad
D
D
Leibovitz
I
I
Bloom
N
N
Goldberg
I
I
Nass
D
D
Engelberg
S
S
Savion
N
N
Eldar
M
M
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2