OBJECTIVETo evaluate whether ultrasonic microbubble destruction (US/MB) could enhance the therapeutic effects of hepatocyte growth factor (HGF) gene transfer for acute myocardial infarction (MI).

METHODSMI was induced by left anterior descending artery ligation in male SD rats. Two to 4 hours thereafter, MI rats were randomly treated with tail vein infusing pc-DNA3.1-HGF plasmid mixed with microbubbles (US/MB-HGF group, n = 18); tail vein infusing pc-DNA3.1-HGF plasmid mixed with saline (US-HGF group, n = 18); tail vein infusing empty plasmid mixed with microbubbles (US/MB-P group, n = 18). All rats were exposed to ultrasound treatment thereafter till contrast imaging disappeared in cardiac region. Rats were sacrificed at 24 hours, 7 days or 14 days, respectively (n = 6 each) and myocardial protein expression of bcl-2 and HGF as well as microvascular density (MVD) were determined.

RESULTSThe myocardial protein expressions of bcl-2 and HGF in US/MB-HGF group were significantly higher than those in US-HGF and US/MB-P groups at 7 days post MI (all P < 0.01) and MVD was significantly higher in US/MB-HGF group (367.6 +/- 17.6) than that in US-HGF (268.9 +/- 0.8) and US/MB-P (186.8 +/- 11.8) groups (all P < 0.05) at 14 days post MI.

CONCLUSIONSUltrasound-mediated microbubble destruction could enhance systemic HGF administration induced myocardial angiogenesis and reduce systemic HGF administration induced myocardial apoptosis in rats with acute MI.