Basic fibroblast growth factor induces myocardial hypertrophy following acute infarction in rats

Mickey Scheinowitz*, Arkady Kotlyar, Schachar Zimand, Dan Ohad, Ilan Leibovitz, Nira Bloom, Iris Goldberg, Devora Nass, Santiago Engelberg, Nafthali Savion, Michael Eldar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 = 0023). 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.

Original languageEnglish
Pages (from-to)585-593
Number of pages9
JournalExperimental Physiology
Volume83
Issue number5
DOIs
StatePublished - Sep 1998

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