Beneficial Effects of Arachidonic Acid during Hemorrhagic Shock in the Dog

Arachidonic acid (AA), precursor of the bisenoic prostaglandins was infused at a rate of 120 /xg/kg per min into the vena cava of dogs subjected to hemorrhagic shock to assess the effects of stimulation of the prostaglandin (PG) synthetase system on the shock state. Hemorrhagic shock was induced by bleeding to a mean arterial blood pressure (MABP) of 40 mm Hg for 150 minutes followed by reinfusion of all remaining shed blood. In sham shock dogs receiving AA vehicle (0.1 M Na2CO3), there were no significant changes in MABP, superior mesenteric artery flow (SMAF), renal artery flow (RAF), PGE2 or PGF2a concentrations, or in cathepsin D or myocardial depressant factor (MDF) activities during a 260-minute experimental period. During oligemia, untreated hemorrhagic shock dogs exhibited dramatic reductions in MABP, SMAF, and RAF which were transiently restored following reinfusion, but markedly decreased 100 minutes after reinfusion. Cathepsin D, MDF, PGE2, and PGF2o values increased significantly in these dogs. AA given during oligemia did not prevent changes in SMAF or RAF, but maintained MABP at near-normal values after reinfusion. AA also significantly protected against the plasma accumulation of both cathepsin D and MDF in hemorrhagic shock dogs. Circulating PGF2c, and PGE, values increased rapidly in AA-treated dogs and plateaued at 3.6 and 4.8 times control values, respectively, during oligemia. Hemorrhagic shock dogs receiving AA plus Na meclofenamate, a PG synthetase inhibitor, were not significantly different from shock dogs receiving vehicle except that the circulating PG concentrations did not increase. Thus, products of the PG synthetase system appear to prevent the plasma accumulation of lysosomal hydrolases and of MDF, and may significantly preserve MABP after hemorrhagic shock in the dog.