Effects of thromboxane synthetase inhibition on maternal-fetal homeostasis in gravid ewes with ovine pregnancy-induced hypertension.
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.
Keith
J C
JC
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Miller
K
K
Eggleston
M K
MK
Kutruff
J
J
Howerton
T
T
Konczal
C
C
McDaniels
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005318:Fetal Heart; D005508:Food Deprivation; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011270:Pregnancy, Animal / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D011725:Pyridines; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; C037787:pirmagrel; D013930:Thromboxane-A Synthase