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Selected hemodynamic, renal, and biochemical parameters were assessed in chronically instrumented third-trimester pregnant ewes and in the same ewes after induction of pregnancy toxemia. Ewes with induced pregnancy toxemia developed hypertension, proteinuria, ketonuria, decreased glomerular filtration rate, decreased cardiac output, and decreased left uterine artery blood flow. Histological and transmission electron microscopy revealed the development of renal morphologic changes consistent with those observed in human pregnancy-induced hypertension. These studies have elucidated that pregnancy-induced hypertension can be produced experimentally in the pregnant ewe. Furthermore, the pathophysiologic features of ovine pregnancy toxemia are similar to those of human preeclampsia, and therefore the sheep provides a suitable animal model to study the human condition, which still remains a major complication of pregnancy, jeopardizing both mother and fetus.

Erythrocyte morphologic characteristics and serum chemistry results were studied in 10 gravid ewes during experimental ovine pregnancy-induced hypertension and subsequent administration of the thromboxane synthetase inhibitors CGS13080 and CGS12970. During the hypertensive period mean arterial blood pressure, plasma thromboxane B2 levels, and serum chemistry results, and electrolyte levels were significantly altered. Parameters returned to baseline values or were improved after drug administration. Erythrocyte morphologic features did not change significantly with the onset of the syndrome. Echinocytosis was present during baseline measurement and persisted throughout hypertension. However, after thromboxane synthetase inhibition, percentages of discocytes increased (p less than or equal to 0.005) with the same frequency that echinocyte numbers decreased (p less than or equal to 0.05). Schistocytes were present throughout the study, and changes in their numbers were not detected. Serum phosphorus, blood urea nitrogen, and bilirubin levels and anion gap rose significantly during hypertension and returned to normal levels after drug treatment. We speculate that CGS13080 or CGS12970, by decreasing thromboxane levels and blood pressure, promoted the normalization of erythrocyte membranes.

Simultaneous maternal indirect blood pressure measurements, electronic fetal heart rate monitoring, and ultrasonographic biophysical profile testing were used to assess maternal-fetal homeostasis in gravid ewes during gestational days 127 to 134 (term 146), during a 72-hour fast, and during treatment with thromboxane synthetase inhibitors CGS13080 and CGS12970. Seventy-five percent of the ewes (12 of 16) developed clinical signs of ovine pregnancy-induced hypertension, including maternal hypertension and fetal depression. In three untreated hypertensive ewes, pregnancy was terminated by spontaneous premature delivery, and one maternal death occurred after an eclamptic seizure. All nine ewes treated with one of the two thromboxane synthetase inhibitors responded to therapy with decreases in blood pressure and resolution of fetal depression. These nine ewes completed gestation, and were delivered at term. These data indicate that therapy with thromboxane synthetase inhibitors in this animal model of preeclampsia results in profoundly beneficial effects and suggest that further studies of thromboxane synthetase inhibitors are warranted in preeclampsia. (Ann J OBSTET GVNECOL 1989;161:1305-13.)