[Effect of TXA2 on renal lysosomal membrane]

ONO-3708, a thromboxane A2 (TXA2) antagonist, was administered by a double blind method during cardiopulmonary bypass (CPB) to study the changes in the plasma and urinary TXB2 levels. Lysosomal enzyme, urinary N-acetyl-beta-glucosaminidase (NAG) was assessed, in order to investigate the in vivo effect of TXA2 on renal lysosomal membrane. Plasma and urinary TXB2 increased significantly (P less than 0.01) during CPB, showing an increase in TXA2 originating from the kidney, in addition to the increased excretion of platelet derived TXA2 during CPB. Urinary NAG increased significantly (P less than 0.01) in the placebo group during CPB and the value of post CPB increased further more (P less than 0.01). In ONO-3708 2 micrograms.kg-1.min-1 group, urinary NAG slightly but not significantly increased during CPB, but was inhibited significantly (P less than 0.01) as compared with two other groups. As shown above, the increased production of TXA2 appears to inhibit the functions of the renal lysosomal membrane in vivo. Furthermore, ONO-3708 has demonstrated a lysosomal membrane stability effect, and it seems reasonable to expect some antishock effect of this drug.