The effect of an oral contraceptive as a preparatory mechanism in the generalized Shwartzman reaction in rabbits.

Abstract

Changes in the blood coagulation parameters (Factor V prothrombin preconvertin and partial thromboplastin time) and the presence of microthrombi in the organs of rabbits pretreated with an oral contraceptive alone (Enavid) or combined with ACTH or chorionic gonadotrophin followed a single injection of endotoxin (E. coli lipopolysaccharide) were compared to changes occurring in pregnant rabbits and in nonpretreated nonpregnant female rabbits following the intravenous injection of the same endotoxin. Final comparison was with changes occurring during the generalized Shwartzman reaction induced by the classical procedure (endotoxin 1.4 mg given as preparatory dose followed 24 hours later by 2.8 mg as a provocatory dose). Modifications in coagulation times seemed to appear after the first hour following endotoxin injection and to reach a maximum 6-12 hours after injection in most rabbits. Such modifications are compatible with a consumption of coagulation factors due to intravascular clotting a phenomenon which was histologically demonstrated by the presence of fibrin thrombi in several organs. Rabbits treated by the classical procedure had the most thrombi and nonprepared normal rabbits had the least; intermediate values were found for pregnant rabbits and those pretreated with hormones. Quantitatively the consumption coagulo was closely correlated to the severity of the intravascular clotting; the higher the former the more disseminated the latter. Results suggest that preparation for the generalized Shwartzman reaction can be obtained in female rabbits by the administration of estrogen and progesterone alone or most probably to a greater extent combined with chorionic gonadotrophin. High similarity was found between pregnant rabbits and rabbits pretreated with oral contraceptives plus chorionic gonadotrophin regarding changes in the coagulation parameters studied and the event of mortality after endotoxin injection.