The effects of uncontrolled hyperglycemia on thrombosis and formation of neointima after coronary stent placement in a novel diabetic porcine model of restenosis

Background Results of recent clinical studies suggest that patients with di abetes mellitus have a higher than normal rate of restenosis after percutan eous transluminal coronary angioplasty or coronary stenting. The mechanism for this exaggerated neointimal response is not known. Objectives To determine the technical feasibility of a model of in-stent re stenosis in swine with streptozotocin-induced hyperglycemia and to compare the late arterial responses to injury induced by placement of oversized cor onary stents in diabetic and nondiabetic animals. Methods Eighteen 25-40 kg castrated male or intact female Yucatan miniature swine aged 6 months were obtained from a commercial supplier. Twelve of th e miniature swine were randomly selected for intravenous treatment with 125 mg/kg streptozotocin to induce a hyperglycemic state. Twelve weeks after t reatment, all animals underwent placement of oversized balloon-expandable s tainless steel stents in the coronary arteries. After 28 days, histomorphom etric analysis of the stented coronary arteries to determine the neointimal responses for the diabetic and nondiabetic animals was completed. Results Sudden death due to stent thrombosis occurred for five of 11 (45%) of the diabetic animals and none of the age-matched nondiabetic control ani mals (P = 0.05), For histology after 28 days, the neointimal response was c orrelated to the extent of arterial injury for the diabetic (r = 0.79, P < 0.0001) and nondiabetic ( r = 0.86, P < 0.0001) animals. The surviving diab etic animals had areas of neointimal (1.67 +/- 0.74 mm(2)) and percentages of in-stent stenosis (28 +/- 14) similar to those of the nondiabetic swine (1.36 +/- 0.40 mm(2) P = 0.26; 22 +/- 6, P = 0.17), Multiple regression ana lysis also demonstrated that arterial injury (P < 0.0001) alone, not hyperg lycemia (P = 0.237), was independently correlated to formation of neointima . Conclusions Uncontrolled hyperglycemia results in greater than normal throm bosis after coronary-stent placement in swine with streptozotocin-induced d iabetes. These data suggest that greater than normal early formation of thr ombus rather than proliferation of smooth muscle cells contributes to reste nosis after coronary stenting in patients with diabetes mellitus. Coron Art ery Dis 11:473-479 (C) 2000 Lippincott Williams & Wilkins.