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

J Thorac Cardiovasc Surg. 2006 Mar;131(3):587-93. doi: 10.1016/j.jtcvs.2005.10.026.


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 microg) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Heptanoates / pharmacology*
  • Male
  • Mammary Arteries / surgery*
  • Rats
  • Rats, Wistar
  • Receptors, Prostaglandin E / agonists*
  • Receptors, Prostaglandin E, EP4 Subtype
  • Sternum / drug effects*
  • Sternum / surgery*
  • Tissue and Organ Harvesting
  • Wound Healing / drug effects*


  • Heptanoates
  • ONO4819
  • Ptger4 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype