In Vitro Tests Fail To Predict The Increased Risk For Ara-Chidonate-Induced Thromboembolism In Rats On Oral Contraceptive (OC) Treatment
Much effort is at present devoted to the search for laboratory tests to predict thromboembolic complications. In this context we have selected OC-treated rats as an experimental model to evaluate whether increased in vivo susceptibility to a thrombotic challenge (sodium arachidonate, NaAA) could be detected by appropriate in vitro tests. Female CD-COBS rats were treated for 10 estral cycles (about 40 days) with an oral combination of lynestrenol (10 mg/kg b.w.) and mestranol (0.3 mg/kg b.w.) dissolved in com oil. Control rats received the vehicle only. After i.v. infusion of NaAA (110 mg/kg b.w.) only 2 out of 24 control rats died within 2 min. Despite the relative resistance of this species to NaAA 10 of the 23 OC-treated rats did not survive NaAA infusion (p = 0.006 compared to controls). Rats made severely thrombocytopenic (less than 2.104 platelets/ul) by a specific antiplatelet antiserum or given aspirin (100 mg/kg b.w.) 1 hour before injection were significantly protected from death following NaAA infusion (p˂0.005) . This indicates that the lethal effect of NaAA involved platelet cyclooxygenase. In vitro experiments however shewed that platelet thromboxane B2 generated with various concentrations of NaAA(0.25- 1 mM) was not significantly different in OC-treated and control rats. Moreover, the minimal concentration of NaAA inducing maximal platelet aggregation was 2.1”0.2 mM in controls and 2.6”0.4 mM in treated rats (p˃0.05) . PGI2 antiaggregating activity generated by aortic specimens incubated with 25 uM NaAA was also similar in both groups. In conclusion, in vitro tests exploring platelet or vascular susceptibility to NaAA failed to identify OC-treated rats as a group at risk for NaAA-induced thromboembolism.