Effects of thromboxane synthetase inhibition on blood cell function and morphology during ovine pregnancy-induced hypertension
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Abstract
Scanning and transmission electron microscopy and platelet aggregometry were employed to study erythrocyte morphology and thrombocyte morphology and function during ovine pregnancy-induced hypertension (OPIH). Nine multiparous gravid ewes were observed during normal pregnancy, OPIH, and thromboxane synthetase inhibitor administration.
Blood pressure, plasma thromboxane B2, serum chemistries and electrolytes, fibrin/fibrinogen degratory products, and total platelet count were monitored throughout the investigation to document the circulatory environment during this syndrome.
Arterial blood pressure, plasma thromboxane B2 levels, and serum chemistries and electrolytes were significantly altered (p≤0.005) during hypertension. However, no change in total platelet count or fibrin/fibrinogen degratory product levels were detected. Collagen-induced platelet aggregation also became abnormal during this time, while ADP-induced aggregatory response remained essentially unchanged. Platelet aggregation changes seemed to correspond to degranulation and swelling of the canalicular tubule system of these cells. Echinocytosis was present during baseline measurement and persisted throughout hypertension. However, changes in shistocyte numbers were not detected.
Administration of the thromboxane synthetase inhibitors CGSl3080 or CGS12970 lowered blood pressure (p≤0.005) and serum thromboxane B₂ (p≤0.005), and. normalized serum chemistries and electrolytes (p≤0.005). Echinocyte numbers decreased (p≤0.05) and discocyte numbers increased (p≤0.005) after treatment. Platelet counts decreased after drug therapy, but normal collagen-induced aggregation was restored. No ultrastructural abnormalities were observed in thrombocytes after treatment.
There is good evidence that thromboxane synthetase inhibition is appropriate and effective treatment for pregnancy-induced hypertension. These data suggest that such therapy is especially indicated in cases complicated by hematologic disorders as evidenced in an ovine model of this syndrome.