1. Ridogrel improves maternal/fetal homeostasis in an ovine model of pregnancy-induced hypertension.
- Author
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Keith JC Jr, Endo Y, Warwick K, Keith KE, Brugh S, and Rowles TK
- Subjects
- 6-Ketoprostaglandin F1 alpha blood, Animals, Disease Models, Animal, Female, Pentanoic Acids pharmacology, Placebos, Pregnancy, Pyridines pharmacology, Radioimmunoassay, Sheep, Thromboxane B2 blood, Fetus physiology, Homeostasis drug effects, Hypertension drug therapy, Pentanoic Acids therapeutic use, Pregnancy Complications, Cardiovascular drug therapy, Pyridines therapeutic use, Thromboxane-A Synthase antagonists & inhibitors
- Abstract
The effects of ridogrel (a thromboxane synthetase inhibitor/endoperoxide receptor antagonist) were assessed in an ovine model of pregnancy-induced hypertension. Maternal serum prostacyclin and thromboxane levels were quanitiated using RIA, and maternal and neonatal coagulation status was assessed. Pregnancy and neonatal outcome were recorded. Ridogrel, (E)-5-[[[3-pyridinyl)[3-(trifluoromethyl)phenyl]methylen]amin++ +] oxy]pentanoic acid, was administered in one bolus dose at 0.1 or 1.0 mg/kg IV, three hours following the onset of a 27 hour magnesium sulfate infusion given hypertensive ewes to prevent maternal seizures. At both doses, ridogrel improved neonatal outcome (0% neonatal mortality in each ridogrel group versus 67% neonatal mortality in the magnesium sulfate group), and ridogrel at 0.1 mg/kg IV normalized birth weights. Abnormalities of maternal platelet function (abnormal or no response to collagen), occurring during the ovine syndrome, resolved following ridogrel treatment. Ridogrel's effects on maternal and neonatal coagulation were more dramatic at the 0.1 mg/kg IV dose. Ridogrel appeared to be beneficial in this model of pregnancy-induced hypertension.
- Published
- 1994
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