The effects of drugs on the arachidonate cascade in experimentally burned rabbits

Platelet reduction and renal dysfunction may occur after major thermal injury and be causally related to changes in the arachidonate cascade. In this article two new drugs, prostaglandin I2 analog OP-41483 (Venopirin) and thromboxane synthetase inhibitor OKY-046 (Cataclot), were tested in addition to aspirin in animal experiments with rabbits. The rabbits were divided into five groups and measurements made before and 8 and 24 hours after burn injury. The results indicate that platelet reduction and renal dysfunction occur within 8 hours after thermal injury in the no-therapy group and renal dysfunction could not be prevented completely even by adequate infusion therapy, but treatment with OP-41483 proved to suppress platelet reduction and improve renal function. Improvement in renal function was also noted in animals treated with aspirin or OKY-046, but platelet reduction could not be prevented by these drugs. Analysis of the time course of changes in thromboxane B2 level and 6-keto prostaglandin F1 alpha level disclosed that animals treated by infusion showed an elevation in thromboxane B2 and a significant elevation in the thromboxane B2/6-keto prostaglandin F1 alpha ratio, whereas animals treated with these three drugs showed a reduction in the thromboxane B2/6-keto prostglandin F1 alpha ratio. These results indicate that an effective measure for prevention of dysfunction of the organs after thermal injury is treatment with drugs that can modify the arachidonate cascade and cause an absolute or relative reduction in TXA2.