PROSTACYCLIN IMPROVES SURVIVAL AND REDUCES MICROCLOT FORMATION IN RABBIT ENDOTOXEMIA
Arachidonic acid metabolites seem to play a pivotal role in the pathophysiology of endotoxin (ET) shock. Therefore, attempts to intervene into the balance of eicosanoids may affect the course of ET shock. Several studies had shown a reduction of ET-induced mortality by non-steroidal antiinflammatory drugs in various animal species.We investigated whether an infusion of prostacyclin (PGI2) has an effect on survival rates and on the incidence of renal microclots in a rabbit shock model, which is based on an intravenous infusion of ET over 4 hours. Thirty animals being exposed to 75 μg/kg x h of lipopolysaccharide B, were allocated to three groups (E, El, EA; n=10 each), either receiving ET only (E), or PGI2 (500 ng/kg x min) simultaneously to ET (El), or aspirin (20 mg/kg) before ET (EA).A control group (C; saline infusion) consisted of 8 animals.At the end of the observation period (8 hours), the mortality of the treated animals (El and EA: 4/10 each) was significantly lower than in group E (8/10). However, only in the PGI2-treated group El a significant reduction of ET-induced glomerular fibrin deposition (GFD) was observed. Indices of GFD after semi-quantitative evaluation of renal slices were 10/27 (E), 1/24 (El), 3/21 (EA), and 0/24 (C). PGI2 exerted a platelet protective effect as shown by higher blood platelet counts (El 61.3 % vs. E 33.4 % of initial values), and a better preserved aggregation (El 60.5 % vs.E 31.7 %) and thromboxane formation capacity (El 52.0 ng/ml vs.E 23.4 ng/ml) of platelet rich plasma stimulated by 5 μg/ml collagen (all values at six hours after the start of ET infusion).ET caused a profound granulocytopenia which was not prevented by PGI2. Furthermore, PGI2 did not affect the ET-induced metabolic acidosis.These data confirm a beneficial effect of prostacyclin during a prolonged endotoxemia in rabbits, which may be a consequence of the known vasodilating, platelet inhibiting and cytoprotective properties of the substance.