Diethylcarbamazine: a leukotriene inhibitor. Effects on red cell deformability in-vitro and in-vivo survival during endotoxemia.
Sepsis is associated with alterations in microcirculatory flow which is demonstrated by impaired O2 delivery and extraction by the peripheral tissues. Leukotrienes, derivatives of arachidonic acid, have been implicated as mediators of the septic process. We investigated the effect of diethylcarbamazine (DEC), a leukotriene inhibitor, on the flow of endotoxin-treated blood through a 5-micron pore polycarbonate filter and on survival in a model of intraperitoneal rat endotoxemia. Endotoxin alone significantly impaired red blood cell flow through the filter. This effect was reversed with DEC treatment. In addition, treatment with DEC significantly reduced rat endotoxemia mortality. This study indicates that impaired red cell deformability may be one factor involved in the alterations in microcirculatory flow following sepsis. Leukotriene inhibition, with DEC improves red cell deformability in vitro, and may account, in part, for the improved survival seen in rat endotoxemia.