Model of Pulmonary Extravasation as an Effect of Neutropenia in Endotoxic Shock in Guinea Pigs

Abstract

A guinea pig model was developed to document the association of polymorphonuclear neutrophils (PMN) decrease with pulmonary leakage after a sublethal infusion of endotoxin (LPS Escherichia coli 0111:B4, 5 µg/min/kg). A control group was prepared in the same manner and given an infusion of vehicle alone. Severe leukopenia developed, mostly expressed in the neutrophil population. There was a decrease in RBC catalase and fibronectin. Plasma leakage in the lung followed the endotoxin infusion, which could indicate endothelial cell damage. The results from the present study suggest an activation of PMN in endotoxin-infused animals, degranulation and release of toxic oxygen species, resulting in pulmonary plasma extravasation.

Endogenously opsonized particles divert prostanoid action from lethal to protective in models of experimental endotoxemia.

“…PGE1 can inhibit the chemotaxis and adhesion of neutrophils to endothelial cells both in vitro and in vivo (7). Since neutrophil extravasation with release of inflammatory mediators is critical in the development of systemic inflammatory disease, these findings have suggested new paradigms for the development of rational therapies, but clinically relevant studies have not been accomplished (8)(9)(10)(11)(12)(13)(14) …”

Dynamic Pulmonary Accumulation of Labelled Neutrophils by Blood Membrane Contact in the Pig

“…It could also imply that other degra nulating products were of importance. It is also possible that a specific relation exists in fibronectin response [23], but the effect of shock other than sepsis on fibronectin is inconclusive [24]. Furthermore,although the PMN shows the same reaction on artificial surface activation in the healthy animal and human [25] as in the uremic, the possibility exists that the uremic cells could experience increased fragility due to either uremia or repeated shear stresses.…”