Validity of a novel ex vivo porcine liver perfusion model for studying haemostatic products.

Abstract

We developed a novel normothermic ex vivo porcine liver perfusion model with whole blood in order to have alternatives for animal experiments in the research and development of new local haemostatic agents. This study aims to assess the construct and content validity of this model. In this study we performed two ex vivo experiments using nine livers and one in vivo experiment using six female Norsvin Topigs pigs: (1) ex vivo liver perfusion for establishing physiological blood parameters of the perfused liver and controlled heparinization, (2) ex vivo liver perfusion with a surgical injury and (3) a surgical liver injury in anaesthetized pigs with and without heparin. Ex vivo coagulation parameters were comparable to in vivo with heparin. Blood gas values and metabolic parameters were comparable between ex vivo and in vivo with heparin, but significantly different compared with in vivo baseline, with the exception of (partial pressure of oxygen (PO2). Activated clotting time (ACT) values significantly differed depending on the heparin doses. The coagulation parameters fibrinogen, activated partial thromboplastin time, prothrombin time and ACT were rather constant during the 4 h ex vivo perfusion. Haemostatic efficacy of commercially available products was comparable between in vivo with heparin and the ex vivo liver perfusion experiment. This novel ex vivo liver perfusion model demonstrates good construct and content validity for at least 4 h of perfusion. The model is an easily accessible, table-top, tunable and effective alternative for the in vivo testing of (new) haemostatic products on their haemostatic properties.Validité d'un nouveau modèle de perfusion hépatique porcin ex-vivo pour l'étude des produits hémostatiques Résumé.