Maternal and fetal hemodynamic effects of diazoxide.
Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.
D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003981:Diazoxide / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005318:Fetal Heart / Q000187:drug effects; D005333:Fetus / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000097:blood; D010920:Placenta; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus; D014655:Vascular Resistance / Q000187:drug effects
D001786:Blood Glucose; D002245:Carbon Dioxide; D003981:Diazoxide; D010100:Oxygen