Marui Akira, Hirose Keiichi, Maruyama Takayuki, Arai Yoshio, Huang Yuhong, Doi Kazuhiko, Ikeda Tadashi, Komeda Masashi
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Sakyo, Kyoto Japan.
J Thorac Cardiovasc Surg. 2006 Mar;131(3):587-93. doi: 10.1016/j.jtcvs.2005.10.026.
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.
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.
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]).
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.
胸骨伤口并发症是冠状动脉搭桥手术中发生的严重事件，在糖尿病患者中尤为常见。前列腺素E2受体有4种亚型，EP4受体的激活可诱导骨再生。本研究探讨了前列腺素E2 EP4受体选择性激动剂在糖尿病大鼠双侧胸廓内动脉离断后正中开胸胸骨愈合中的作用。
通过单次腹腔注射链脲佐菌素建立血糖水平大于400mg/dL的糖尿病Wistar大鼠模型。16只糖尿病大鼠行正中开胸及双侧胸廓内动脉离断术后，8只大鼠在胸骨后表面给予EP4激动剂（300μg）（EP4组），8只大鼠不接受任何治疗（对照组）。术后4周评估胸骨愈合情况及胸骨伤口并发症的发生率。
对照组5只大鼠发生胸骨伤口并发症，而EP4组仅1只大鼠发生（P<0.01）。组织学检查显示，仅EP4组胸骨几乎完全愈合，充满再生骨组织。双能X线吸收法评估的骨矿物质含量和骨矿物质密度，EP4组均高于对照组（骨矿物质含量：71.7±12.1mg对48.9±11.7mg[P<0.01]；骨矿物质密度：66.8±14.6mg/mm²对47.9±6.3mg/mm²[P<0.05]）。
前列腺素E2 EP4激动剂可加速糖尿病缺血性胸骨的愈合，降低胸骨伤口并发症的发生率。该方法可能有助于降低高危患者的胸骨坏死发生率，或使双侧胸廓内动脉在冠状动脉搭桥手术中得到更广泛应用，即使是糖尿病患者。
