ABSTRACT

The choice of an animal model for the study of postprandial coagulation factor VII activation

Aage Kristian Olsen1,2,3; Else-Marie Bladbjerg1; Peter Marckmann2 and Axel Kornerup Hansen3
1Department for Thrombosis Research, the University of Southern Denmark, and Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg; 2Research Department of Human Nutrition, and 3Department of Pharmacology and Pathobiology, the Royal Veterinary and Agricultural University, Frederiksberg, Denmark

The development of animal models is a central part of laboratory animal science, and the choice of a relevant animal species is crucial. The aim of the present studies was to compare the Göttingen minipig and the LEW/Mol rat as models of postprandial factor VII (FVII) activation in humans. The minipig was chosen due to similarities to human fat absorption and metabolism, atherosclerosis, and blood coagulation. The rat was chosen due to similar fat absorption and blood coagulation, but seems less attractive than the minipig, due to a different fat metabolism and resistance against atherosclerosis. In the first study seven minipigs received four g fat (Intralipid®)/kg through a gastric tube. In the second study 100 LEW/Mol rats received the same metabolic fat-dose or isotonic glucose (placebo) through a gastric tube. Blood samples were drawn before and after the fat-load and analysed for triglycerides, activated FVII (FVIIa), FVII coagulant activity (FVIIc), and FVII amidolytic activity (FVIIam). In both animal species plasma triglycerides were significantly raised as in human studies. In minipigs, FVIIc decreased significantly, but no changes were observed in FVIIa, and FVIIam. In rats, FVIIa increased significantly (as in humans), and no changes were observed in FVIIc and FVIIam. In summary, the rat, but not the minipig, is a useful animal model for the study of postprandial FVII activation and its consequences. It is unknown why minipigs do not activate FVII after high-fat meals, but it is possible that the role of FVII plays minor in porcine coagulation compared to rat and human coagulation. However, as a negative model, the minipig may be suitable to study the mechanism leading to FVII activation. In conclusion, the choice of animal models in the field of nutrition and ischaemic heart disease is crucial. Even though literature studies indicate that the minipig is a more attractive model than the rat in this research field, this is not the case for studies on postprandial FVII activation.
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