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F5. Bio-CABG, not only arteriogenesis but also a “bypass” surgery, to expand the surgical arena in the era of drug eluting stents --- a pre-clinical study.
Kiyoaki Takaba, Shintaro Nemoto, Yoshiaki Saji, Chunli Jiang, Tadashi Ikeda, Takashi Azuma, Shinichi Urayama, Sadami Tstutsumi, Yasuhiko Tabata, Masashi Komeda; Kyoto, Japan

Objective: Many patients with severe /diffuse coronary lesions are not eligible for conventional therapies . Although various methods of angiogenesis have been studied, few clinical studies have shown the development of angiographycally “visible” collateral effects. In order to provide the patients with revascularization whose benefits are comparable to those of CABG for low-risk patients, we developed a new surgical technique, a combination of angiogenesis induced by basic Fibroblast Growth Factor (bFGF) and omentum (as a connector) with gastroepiploic artery (GEA, as an extracardiac blood source), namely biological CABG (Bio-CABG). Our previous study showed the excellent results of Bio-CABG in acute myocardial infarction model. The purpose of this study was to demonstrate that Bio-CABG could induce “visible” angiographic effects and functional benefits in chronic ischemic myocardium.
Methods: Chronic ischemic model was created by placing a constrictor on the left circumflex artery (LCx) in adult rabbits. Four weeks later the animals were divided into three groups; Group FG (n=8) in which a gelatin sheet incorporating 100 μg bFGF was placed over the ischemic region followed by wrapping the omentum with GEA, Group F (n=8) in which merely the bFGF sheet was placed and Group N (n=4) in which no treatment was done.
Results: Four weeks after each treatment, echocardiography showed greater fractional shortening in Group FG than in Group F and Group N (Group FG :32±6 vs. Group F:28±4 %, p<0.01, Group N: 20±3% ). Cine-magnetic resonance imaging (MRI) showed greater wall thickening of treated area at end-systole in Group FG than Group F (4.46±0.58 vs. 3.82± 0.37 mm p<0.01). Coloured microsphere assays showed higher perfusion of LCx territory in Group FG than Group F (2.83±0.72 vs. 2.25±0.51 ml/min/g, p<0.01). Importantly, perfusion was decreased after clamping GEA pedicle in Group FG (before clamping: 2.83±0.72 vs. after: 1.93±0.59 ml/min/g, p<0.01). Microscopic examination revealed that arterioles (>50μm in diameter) were identified more in Group FG than Group F (31±4 vs. 26±5 vessels/mm², p<0.01). The particles (>150μm in diameter) were identified in the sample that was ink-injected via GEA suggesting sizable biological “anastomosis” of Bio-CABG. In vivo GEA angiography showed direct to-and-fro visible communications between GEA and LCx in group FG suggesting extra cardiac blood source not just enhances angiogenesis but induces arteriogenesis in chronic ischemic myocardium.
Conclusions: “Bio-CABG” induced arteriogenesis with biological “anastomosis”, and provided excellent blood flow, which was comparable to CABG in the chronic ischemic model. The method may expand the surgical indication for patients with severe coronary disease.

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