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Laboratory and Animal Investigations |

Fibroblast Growth Factor-2 Induces Recovery of Pulmonary Blood Flow in Canine Emphysema Models*

Shigeyuki Morino, MD; Tatsuo Nakamura, MD; Toshinari Toba, MD; Mitsuru Takahashi, MD; Toshihiro Kushibiki, MD; Yasuhiko Tabata, MD; Yasuhiko Shimizu, MD
Author and Funding Information

*From the Institute for Frontier Medical Sciences (Drs. Nakamura, Toba, Takahashi, Kushibiki, Tabata, and Shimizu), Kyoto University, Kyoto; and Division of Surgical Oncology (Dr. Morino), Nagasaki University School of Medicine, Nagasaki, Japan.

Correspondence to: Shigeyuki Morino, MD, Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; e-mail: morinos@frontier.kyoto-u.ac.jp



Chest. 2005;128(2):920-926. doi:10.1378/chest.128.2.920
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Study objectives: Fibroblast growth factor (FGF)-2 is one of the most powerful angiogenic growth factors to be evaluated as an agent for the promotion of angiogenesis. The aim of this study is to investigate whether intratracheal administration of controlled-release FGF-2 microspheres restores pulmonary function in beagle dogs with emphysema.

Design: Randomized, controlled, experimental animal study.

Subjects: Eighteen Wister rats and 15 adult beagle dogs.

Methods: In the rat study, we compared the time profiles of the radioactivity remaining after intratracheal injection of 125I-labeled FGF-2, either incorporated with the controlled-release microspheres or as an aqueous solution. In the dog study, elastase-induced emphysema models were developed in 10 animals, classified into the following three groups: control group (n = 5), emphysema model with empty microspheres-treated group (FGF − group, n = 5), and emphysema model with FGF-2 containing microspheres-treated group (FGF + group, n = 5).

Results: In the rat study, controlled-release microspheres maintained higher whole-lung FGF-2 concentrations after intratracheal administration. In the dog study, Pao2 in the FGF + group was significantly higher than in the FGF − group after treatment. Pulmonary perfusion dynamic MRI revealed significant improvement in the signal intensity of damaged lung with the FGF + group. Linear intercept of the FGF + group was significantly reduced than the FGF − group.

Conclusion: Results indicate that intratracheal administration of FGF-2 induced an increase in pulmonary blood flow in the damaged lung and led to recovery of pulmonary function. The controlled-release microsphere system increased the effectiveness of FGF-2.

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