Dihydroergotamine causes fetal growth retardation in guinea pigs

Dihydroergotamine is a vasoactive drug which enhances venous tone, central blood volume and cardiac output but has variable effects on arterial tone. Its effect on the uterine arterial circulation is unstudied and yet dihydroergotamine is widely used to treat postural hypotension in pregnant and nonpregnant women. For this reason we undertook studies to determine if its chronic use had any adverse effect on the placental arterial circulation and fetal growth in an animal model. We administered dihydroergotamine (14 micrograms/kg/day) to pregnant guinea pigs with 2-4 fetuses from day 30-60 of pregnancy. At term under light ketamine anaesthesia, we measured maternal arterial blood pressure and blood flow to myometrium, placenta, skin and skeletal muscle using left ventricular injection and standard sampling techniques. Vascular resistance was calculated from arterial blood pressure and blood flow. When controlled for litter size, both fetal weight and the fetal weight/placental weight ratio were significantly less (P less than 0.001) in the dihydroergotamine group (-21% and -11% respectively). Placental blood flow was decreased by 51% (P less than 0.01) whereas myometrial blood flow, skin blood flow and muscle blood flow were not significantly altered. There was no significant difference in mean arterial blood pressure but placental vascular resistance was increased (+45%, P less than 0.05) while it was unchanged in myometrium and skin and decreased in skeletal muscle (-51%, P less than 0.05). Chronic administration of dihydroergotamine at a clinical dosage level has a constrictive effect on the placental vasculature of guinea pigs with a subsequent adverse effect on flow and fetal growth.