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J Thorac Cardiovasc Surg 2006;131:587-593
© 2006 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Prostaglandin E₂ EP4 receptor–selective agonist facilitates sternal healing after harvesting bilateral internal thoracic arteries in diabetic rats

^a Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto Japan
^b Minase Research Institute, Ono Pharmaceutical Company, Osaka, Japan
^c Takeda Hospital, Kyoto, Japan

Received for publication May 28, 2005; revisions received September 21, 2005; accepted for publication October 20, 2005.

^_* Address for reprints: Masashi Komeda, MD, PhD, Professor and Chairman, Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara, Sakyo, Kyoto, 606-8507 Japan (Email: komelab{at}kuhp.kyoto-u.ac.jp).

OBJECTIVE: Sternal wound complications are devastating events occurring in coronary artery bypass surgery, particularly in patients with diabetes. Prostaglandin E₂ receptors have 4 subtypes, and the activation of the EP4 receptor induces bone regeneration. The present study investigated the utility of a prostaglandin E₂ EP4 receptor–selective agonist in sternal healing after median sternotomy with the removal of the bilateral internal thoracic arteries in diabetic rats.

METHODS: Diabetic Wistar rats with blood glucose levels of greater than 400 mg/dL were established by means of a single intraperitoneal injection of streptozotocin. After median sternotomy and bilateral internal thoracic artery removal in 16 diabetic rats, 8 rats were administered the EP4 agonist (300 µg) on the posterior table of the sternum (EP4 group), whereas 8 did not receive any treatment (control group). Sternal healing and incidence of sternal wound complications were evaluated 4 weeks after the operation.

RESULTS: Sternal wound complications developed in 5 rats in the control group but in only 1 rat in the EP4 group (P < .01). Histologic examination revealed an almost completely healed sternum filled with regenerated bone tissue only in the EP4 group. Both bone mineral content and bone mineral density, as assessed with dual-energy x-ray absorptiometry, were higher in the EP4 group than in the control group (71.7 ± 12.1 vs 48.9 ± 11.7 mg for bone mineral content [P < .01] and 66.8 ± 14.6 vs 47.9 ± 6.3 mg/mm² for bone mineral density [P < .05]).

CONCLUSIONS: The prostaglandin E₂ EP4 agonist accelerated the sternal healing and decreased the incidence of sternal wound complications in the diabetic ischemic sternum. This method might help in decreasing sternal necrosis in high-risk patients or permit wider application of bilateral internal thoracic arteries in coronary artery bypass surgery, even in patients with diabetes.

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