Establishing an Animal Model of Atherosclerotic Plaque Rupture and Thrombosis by Liquid Nitrogen

Objective To establish a simple,economical,practical animal model of atherosclerotic plaque rupture and thrombosis suitable for the study of human atherosclerosis.Methods 21 healthy male New Zealand white rabbits were randomly divided into two groups: group A(n=11) and group B(n=10).Rabbits in group A underwent cold-induced endothelial injury with liquid nitrogen in the right carotid arteries,then were given a high-fat diet for eight weeks.Rabbits in group B were only fed a high-fat diet for eight weeks.After completion of the preparatory regimen,triggering of plaque rupture was attempted by local injection of liquid nitrogen in two groups.Before and after triggering,the serum lipid levels,hsC-RP,MMP-9 and PAI-1 of plasma were assayed.48 hours after triggering,all rabbits were killed by an overdose of intravenous pentobarbital sodium.The right carotid arteries were quickly removed for light microscopy,electron microscopy and immunohistochemistry.Results After 8 weeks of high-fat diet,the serum lipid levels were significantly higher than baseline at the beginning of the experiment.After triggering in group A,the concentration of hsC-RP、MMP-9 and PAI-1 was significantly higher than the levels before triggering.All rabbits in group A had an acutely ruptured plaque and rupture-driven occlusive thrombus formation 48 hours after triggering,but none in group B.Importantly,the cold-induced lesion in our model is reminiscent of human atherosclerotic plaques in terms of architecture,cellular composition,growth characteristics,and patterns of lipid accumulation.Conclusions This study demonstrated that atherosclerotic plaque rupture and thrombosis could be established by cold-induced endothelial injury with liquid nitrogen,which is simple,fast and inexpensive.The novel model can be used to study the pathogenesis and therapies of atherosclerotic plaques lead to acute coronary events and stroke.