Adult respiratory distress syndrome (ARDS) is often associated with impaired fibrinolysis
and appearance of microemboli in the lung. Increased production of PAI, associated
with acute lung injury, may contribute to this process. In patients at risk of developing
microembolic complications, aeteinistration of dextran reduced the incidence of ARDS.
Accordingly, we studied the effect of dextran adninistration on plasma PAI levels
in a rabbit model of endotoxin-induced lung injury and in patients. E coli endotoxin
(500 μg/kg bw, infused over 5 min) was administrered to three groups of anesthetized,
ventilated rabbits; 10 rabbits were pretreated and maintained with a 10% dextran-40
infusion (20 ml/kg bw), 6 received a 3% albunin solution (20 ml/kg bw) and 8 control
rabbits received saline. Plasma PAI levels were measured by chrcmogenic assay. By
180 minutes after endotoxin infusion, PAI levels increased from 28 ± 6 to 155 ± 7
U/ml in the saline group, to 152 ± 10 U/ml in the albumin group and to 85 ± 8 U/ml
in the dextran group.
24 surgical patients were given 500 ml Dextran 70 (Macrodex) and PAI and t-PA were
determined before, during and after dextran. PAI levels decreased 6 ± 8 U/ml during
dextran infusion and 11 ±11 U/ml (26 per cent) after dextran, and was significantly
decreased after correction for hemodilution. t-PA antigen levels were not changed
due to dextran. Dextran thus has an effect on PAI levels which is not due to release
of t-PA. Dextran by decreasing PAI levels may have unique salutary effects on fibrinolysis
which may be important in the prevention of thrombotic disorders.
