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Purpose: Restenosis after percutaneous coronary intervention is still a problem particularly with regard to diabetic patients and their increased risk profile. Therefore a suitable animal model is important to investigate and improve therapeutic options. This study aimed to develop a reproducible model of advanced coronary atherosclerosis with induction of hyperlipidemia and/or hyperglycemia in domestic pigs.
Methods: Four domestic crossbred pigs were fed with two different fat diets (group 1 and 2) for 8 ? 13 weeks. The animals in group 2 additionally received 150 mg/kg Streptozotocin (STZ) in three doses on consecutive days to induce diabetes. Six pigs were fed a standard pig chow for 13 weeks and served as a control (group 3). Serum lipid and plasma glucose values were analyzed, histochemical staining for morphometric analysis and immunohistochemistry were performed.
Results: Pigs on hyperlipidemic diet showed elevated serum lipid levels (total cholesterol: 5,05±1,45 mmol/l (group 1) and 5,03± 2,41 mmol/l (group 2) vs. 2,09±0,23 mmol/l (group 3)). The lipid levels declined subsequently, but not to physiological levels. None of the STZ-treated pigs did show a sustained elevation of plasma glucose (mean glucose before STZ-injection: 5,11±0,94 mmol/l and thereafter: 6,03±2,39 mmol/l) or a decline in pancreatic beta cells. Histopathologic evaluation revealed fatty streaks containing foam cells as an initial stage of coronary atherosclerosis.
Conclusions: Our data show that it is not possible to establish a severe atherosclerotic and diabetic model suitable for interventional vascular experiments in domestic pigs. This may be due to different STZ sensitivities among species. However, hyperlipidemia induced early pathological lesions in coronary arteries resembling initial stages of atherosclerosis without severe luminal narrowing.