Abstract 3615: Placental Growth Factor Increases Regional Myocardial Blood Flow and Function in a New Porcine Model of Chronic Myocardial Ischemia
Background. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, has a distinct biological profile with a predominant role in pathological angiogenesis without affecting quiescent vessels in healthy organs. We tested whether systemic administration of recombinant human (rh) PlGF improves regional myocardial blood flow and systolic function recovery in a new porcine chronic myocardial ischemia model.
Methods and Results. We implanted a reduction stent in the mid-portion of the LAD, inducing a flow limiting stenosis greater than 80% and measured systemic hemodynamics, regional myocardial function using 3.0 T magnetic resonance imaging, and blood flow using colored microspheres injection 4 weeks later. Animals were randomized in a blinded way to chronic rhPlGF infusion (15μg/kg/day, n=11) or PBS (con, n=10) for 2w via a minipump connected to the jugular vein. Regional myocardial perfusion and function in the ischemic, border and remote zones were again measured after 8w and neovascularization was evaluated on lectin-and smooth muscle (SM) actin-stained sections. Infusion of rhPlGF transiently increased serum levels (1153±180 vs 33±19 pg/ml in con, p<0.001) without affecting systemic hemodynamics and increased regional myocardial blood flow to the ischemic area from 4 to 8w (from 0.46±0.1 to 0.78±0.1 ml/min/g vs from 0.45±0.1 to 0.49±0.1 ml/min/g in con, p<0.05) and regional wall motion (from 3.8±0.18 to 4.5±0.22 mm vs from 4.3±0.26 to 4.3±0.30 mm in con, p<0.05). Similarly, rhPlGF increased regional perfusion and systolic wall thickening from 4 to 8w in the border zone (+85% and +42% respectively, vs +19% and +7% in con, p<0.05). Functional improvement after rhPlGF was accompanied by increased myocardial vascularization in the ischemic zone as indicated by the semi-quantitative scoring of lectin-and SM-actin positive clusters (p<0.05 vs con) and by enlarged cardiomyocyte size (p<0.05 vs con).
Conclusions. Systemic rhPlGF infusion significantly enhances regional blood flow and contractile function of chronically ischemic myocardium without adverse local or systemic effects. PlGF is an attractive therapeutic strategy for chronic myocardial ischemia.