Cardiovascular and Haemostatic Changes in a Rabbit Microsphere Model of Pulmonary Thrombosis

  • Line Olrik Berthelsen Novo Nordisk A/S, MÃ¥løv
  • Henrik Duelund Pedersen Zealand Pharma A/S, Glostrup
  • Annemarie Thuri Kristensen Department of Small Animal Clinical Sciences, Faculty of Life Sciences, University of Copenhagen
  • Mikael Tranholm Novo Nordisk A/S, MÃ¥løv

Abstract

In order to further understand the pathogenesis of disseminated intravascular coagulation (DIC), to diagnose the condition in the early stage and to provide effective therapeutic intervention, valid and clinical relevant animal models are needed. Microvascular pulmonary thrombosis is one of the hallmarks in DIC. In the search for markers of microvascular pulmonary thrombosis in DIC, the present study evaluated local pulmonary effects of microvascular pulmonary thrombosis caused by polystyrene microspheres, generally assumed to be inert. Simultaneously the haemostatic system was evaluated to investigate whether microspheres are truly inert in a rabbit model of microvascular pulmonary thrombosis.

Cardiovascular and haematological parameters were measured at three time points over a 30 minute period from rabbits administered 45 μm microspheres as a single bolus dose of 0.3, 6, 16 or 32 μl microspheres/ml blood. Injection of 0.3 μl microspheres/ml blood resulted in no changes. Injection of 6 μl microspheres/ml blood resulted in a minor increase in cardiovascular parameters whereas injection of 16 μl microspheres/ml blood resulted in significant changes of cardiovascular parameters without impact on haemostatic parameters. A lethal effect was shown after injection of 32 μl microspheres/ml blood.

With i.v. injection of microspheres we succeeded in establishing an inert mechanical model of fixed size microvascular emboli in the lung vasculature of the rabbit. We showed that selected cardiovascular parameters rapidly and dose dependently reflect obstructions in the pulmonary vasculature and therefore could be very valuable and reliable parameters in experimental models of disseminated intravascular coagulation for early detection of microvascular pulmonary thrombosis.

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