Quantification of the Effect of Lipo-PGE1 on Angiogenesis

Lipo-Prostaglandin E1 (PGE1) is widely used for its beneficial effects on vasodilation, platelet disaggregation, blood viscosity, fibrinolysis, and angiogenesis. Although the angiogenetic effect of Lipo-PGE1 is critical for recovering ischemic tissues, little research has been undertaken to quantify its effects on angiogenesis. Fifteen rabbits were used to assess the effect of Lipo-PGE1 on neovascularization. Merocel® (Tampon nasal standard) and Alloderm® (acellular human dermal matrix) of same size were implanted separatealy under the back skin flap to act as matrices for vessel growth. Lipo-PGE1 was injected intravenously for 2 weeks at 3.0 μg/kg in experimental group of 8 rabbits and these animals were compared with a control group of 7 untreated animals. Blood flow was measured using the ^99mTcO4- clearance technique and mean blood clearance half time (T1/2) was calculated at 2 weeks and compared in the 2 groups. Washout radioactivity from Merocel® implants was measured using a collimated gamma-scintillation camera for 30 minutes. Merocel® and Alloderm® were removed and newly formed vessels were counted by CD31 staining under a light microscope at 400X. Statistical analysis was performed. ^99mTcO₄^- clearance rate was obtained in all rabbits. Mean clearance half time was 4005 ± 2161.3, 13840 ± 4644.6 seconds in experimental and control group , respectively in 1 X 2 X 1.5 cm (p = 0.0125), and 1560 ± 1174.7, 3405 ± 807.03 seconds respectively in 2 X 2 X 1.5 cm (p = 0.0413). Histological examinations revealed that the mean numbers of newly formed vessels in the Merocel^® in the experimental and control groups were 11 ± 1.58, 7.8 ± 1.71, respectively in 1 X 2 X 1.5 cm (p = 0.0501), and 20.19 ± 12.47, 12.33 ± 3.25 respectively in 2 X 2 X 1.5 cm (p = 0.02679). However, the low numbers of newly formed vessels in Alloderm® at 2 weeks prevented analysis. Lipo-PGE1 was found to be effective at promoting angiogenesis in a rabbit matrix model. Considering the survival mechanism of composite grafts, Lipo-PGE1 appears to potentiate in inosculation process and to accelerate neovascularization, which might promote effective therapeutic angiogenesis.