| dc.description.abstract | Over the last decade extracorporeal life support (ECLS) has been increasingly used in the management of life-threatening respiratory failure in children and in adults. The life support technology, however, is associated with several side effects, and bleeding complications are seen in one-third of the patients treated. The bleeding complications have been attributed to the systemic heparinisation and to an ECLS-induced thrombocytopenia and platelet dysfunction. The objectives of the present work were to: (I) evaluate an in vitro model for extracorporeal circulation, with emphasis on platelet changes, (II) evaluate the individual effects of different devices of the extracorporeal circuit on platelet consumption and activation, (III) evaluate the effect of a serine protease inhibitor on the ECLS-induced platelet damages and coagulation changes, and (IV) evaluate the effect of nitric oxide, administered to the oxygenator sweep gas, on the platelet consumption and activation during simulated extracorporeal circulation and during cardiopulmonary bypass surgery. We found that our in vitro model for extracorporeal perfusion mirrored the effects on platelets induced by ECLS systems in clinical situations. The platelet changes were equally pronounced in the circuits with a centrifugal pump as in those with a roller pump. A hollow fibre oxygenator seemed to be superior compared to a membrane oxygenator, as reflected by higher platelet counts, lower b-thromboglobulin levels and preserved platelet membrane glycoprotein (GP) Ib expression. A synthetic serine protease inhibitor - Nafamostat mesilate - was found to reduce activation of platelets and coagulation. Also, nitric oxide, added to the oxygenator sweep gas during simulated extracorporeal perfusion reduced platelet consumption and activation. However, these latter findings could not be reproduced in an in-vivo study on adults undergoing open heart surgery. In conclusion, our experimental model of extracorporeal perfusion is very useful for further improvements of the ECLS technique. Different strategies can be evaluated under well controlled experimental conditions, before full sized clinical studies are launched. | en |
