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(Circulation. 2001;104:I-325.)
© 2001 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

Gelatin Sheet Incorporating Basic Fibroblast Growth Factor Enhances Healing of Devascularized Sternum in Diabetic Rats

Atsushi Iwakura, MD; Yasuhiko Tabata, PhD; Nobushige Tamura, MD; Kazuhiko Doi, MD; Kazunobu Nishimura, MD; Tatsuo Nakamura, MD; Yasuhiko Shimizu, MD; Masatoshi Fujita, MD; Masashi Komeda, MD

Department of Cardiovascular Surgery (A.I., N.T., K.D., K.N., M.K.), Kyoto University Graduate School of Medicine, Kyoto, Japan; Institute for Frontier Medical Sciences (Y.T., T.N., Y.S.), Kyoto University, Kyoto, Japan; and College of Medical Technology (M.F.), Kyoto University, Kyoto, Japan.

Correspondence to Masashi Komeda, MD, Professor and Chairman, Department of Cardiovascular Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507. E-mail masakom{at}kuhp.kyoto-u.ac.jp

Background— Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic patients. We have reported that a gelatin sheet that incorporates basic fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in normal rats. This study evaluated the effects of the above method for sternal healing in diabetic animals.

Methods and Results— Diabetic Wistar rats with blood glucose levels >400 mg/dL and body-weight loss >20 g were established by a single intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated bFGF (100 µg/sheet) on the posterior table of the sternum (FGF group, n=9) or no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the preoperative level (106±10% versus 82±9%, P<0.01), and marked angiogenesis was also observed around the sternum in the FGF group (30.5±3.2 versus 15.8±2.7 vessels/unit area, P<0.01). Deep sternal wound complications developed in 5 control rats but only in 1 rat in the FGF group (P<0.05). In the FGF group, histological examination showed improved sternal healing (excellent in 6 rats and slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray absorptometry was greater in the FGF group (75.9±18.1 versus 48.9±10.7 mg, P<0.05). Bone mineral density of the sternum was similar between the 2 groups.

Conclusions— A gelatin sheet that incorporates bFGF may offset sternal ischemia and accelerate sternal bone regeneration and healing, even in diabetic patients.

Key Words: angiogenesis • growth substances • diabetes mellitus